Kharrazian Institute – Neuroinflammation, Course One ...

Microsoft Word - KI-course-one-session-1-transcript.doc1 Kharrazian Institute – Neuroinflammation, Course One, Session 1 Introduction to Neuroinflammation Concepts
© 2019, Kharrazian Institute LP Presented by Dr. Datis Kharrazian
Dr. Kharrazian: Thank you for being part of this neuroinflammation course. I have a lot of information to share with you. And we're gonna go pretty fast-paced. The way I've really organized this course is we have real cases to go through. We were very lucky to have some of my patients that were willing to share their cases with us. The patients I took for the cases are not easy patients. I'm not showing you guys patients that are easy to manage. I'm showing you guys complex patients. I'm showing patients that I'm having a hard time struggling and researching and doing things. And I'm hoping for everyone's input with these cases too. So, they're real-life cases.
They're not gonna be the, "You do this one thing, and everything's perfect, and birds are flying everywhere, and you're awesome." It's not that. That, as you guys know, is not real practice. So, just like many of you, I'm frustrated all the time going to seminars. And you go to seminars. Everyone presents a model. And that model is the way you do it. And it's like, "Is it really? How do you know? Maybe it's not. Maybe there are too many variables we just can't discuss in a weekend. Maybe patients are more complex than they seem." So, what I'm trying to do with the development of the Kharrazian Institute is really just make it as clinical as we can make it. And what that means is we follow patients on our Facebook page. And we talk to people. And we share stories and cases. And it's not always easy. And then we update research papers. And we go through all the material in a clinical fashion. So, the important thing about this topic is this is the topic that is totally overlooked because people here with neuroinflammation go, "I know it. Glial cells get inflamed. Give him some fish oils, some anti- inflammatory. So, I'll just treat the gut. That'll fix it because I went to a seminar. If I fix the gut, that'll fix the brain. So, I'm just gonna start with the gut. That's where you start anyways, right? No. It's more complicated than that. And you guys, here's the key clinical thing you need to understand right away. There are some patients that don't just have neuroinflammation. They have what's called glial cell priming. We're gonna talk about that. That means their brain structure has forever been changed. You cannot treat them and expect the same results as patients that do not have glial cell priming. When you look at kids with developmental disorders, look at kids with autism, and look at people that have traumatic brain injuries, look
2 Kharrazian Institute – Neuroinflammation, Course One, Session 1 Introduction to Neuroinflammation Concepts
at people that have unresponsive depression, many of them have what are called primed glial cells. You, as clinicians, have to make sure you understand the studies and research behind what that means to you as a clinician because they're not gonna be the patient you would expect normal results with. So, if there's one key thing that you are gonna definitely hopefully take away from this weekend is picking up which patients have primed glial cells and how they're completely different than every other patient. And I will guarantee you that that will be a subset of patients that are walking around from one practitioner to the next to the next to the next. And they come in with their stack of functional medicine tests and conventional tests. And they're gonna be going, "I know what to do." And you're gonna go, "Wow. This is so obvious. This is glial priming. We need to totally address this differently. And it's not this short window of just restoring the gut and everything's better or putting up some nutraceuticals. It's not that easy. And so, we're gonna go through all those different approaches. So, that's the key thing. So, I have many academic loves in my life besides my family, my wife and daughter. But my academic love is neurology. I love neurology. And I have made a concentrated effort to know how to do a very good neurological exam and to never miss anything. But glial cell priming and glial cell neuroinflammation has nothing to do with everything I've learned in the last 20 years trying to learn neurology. It makes the neurological pathways completely different. So, let me explain what I mean to you. When you look at the brain, only 10 percent of the brain cells are neurons. That's it. Do you guys know that? 90 percent of the brain are glial cells. That's in humans. Now in worms, 25 percent of the brain are glial cells. In mice, 65 percent of the brain are glial cells. In humans, it's 90 percent. In elephants, 97 percent of the brain are glial cells, which tells you a lot maybe. We're still learning a lot about them. So, when you look at glial cells, glial cells are a key part of brain function and brain integration, which most people don't talk about because they're so fixated on the neuron, on the neurological pathway and the tract and the cortex and the region and left brain, right brain, all this stuff. And sometimes, if you do not address the glial system and understand it, you're not going to help patients with brain-related disorders as well as you could. Now when you
look at these glial cells, we have to know that there are different types of glial cells. So, there are astroglia cells. There are about 15 percent to 20 percent of the 90 percent of the cells in the brain are astroglia cells. Of the 90 percent of the cells in the brain, 15 percent of them are microglial. And the rest of those are oligodendrocytes. They behave differently. So, we wanna know how they behave. These things impact the blood brain barrier. There's so much focus on the leaky gut syndrome. And people totally have ignored blood brain permeability. Blood brain permeability is more complicated than leaky gut syndrome. And it's just as common. And it will devastate people's lives. And it's more so than just inflammation because one of the key things you also understand with the brain right away before we get into stuff with more debt, there are no pain fibers in the brain. There are no nociceptors in the brain. So, the brain's inflamed. You don't have pain. People that have pain or they're vascular from headaches, migraines, those are vascular phenomenons. Those are not inflammation. So, when people have brain inflammation, they lose function. They get depression. We'll go over the whole pattern of the sickness syndrome and all the things that take place. But they do not have pain. Neuroinflammation does not cause pain. It causes loss of brain function. It causes loss of motivation. It causes inability to get out of bed. It causes a person to not have great endurance, to have fatigue all the time. That's how brain inflammation presents. So, it's not the headache patient. It's not the person suffering from migraines and so forth. It's the person who doesn't know why they can't function anymore that is in trouble. That's the case. And that's one of the key first things of today. So, let me show you the plan that we have today. We're gonna go into the introduction in a second here, give you some key concepts about neuroinflammation. And then the very first important clinical thing we need to make sure everyone understands is how to pick up on neuroinflammation. How does it present into your office? Because I guarantee you they're not gonna come in an say, "I have neuroinflammation." Chief complaint. Neuroinflammation. They're never gonna do that. And they're especially not gonna go, "Glial cell primed."
They will never tell you that. So, how do you pick them up? And they have a diverse presentation. It's everything from childhood developmental disorders to autism to someone who had a traumatic brain injury 10 years ago and doesn't know why they're falling apart now to chronic anxiety syndromes to chronic depression, doesn't respond to antidepressants, someone who's got a neurodegenerative disease, someone who's 30, now has cognitive decline. You gotta start suspecting neuroinflammation. And then you gotta work it backwards, which we're gonna teach you this weekend. So, the first thing is you have to understand how to pick up on neuroinflammation. And then also, the severity of the neuroinflammation. So, we're gonna go through and talk about understanding clinical severities of neuroinflammation. And then in part one, which is today, we're gonna go into lifestyle and dietary applications. So, the goal of today is different than the goal of tomorrow, the goal of part one. The goal of part one is to teach you how to pick up a neuroinflammation, understand the severities, figure out how to differentiate primed glial cells versus not primed glial cells. That will completely change your clinical outcome and your prognosis and your clinical management. Then the next goal is, "Well, they have brain inflammation. What do you do? What's all the studies that have ever been published on how diet changes neuroinflammation?" I'm gonna summarize all that for you and show you how we use it clinically. And then what are all the nutraceuticals ever published on this? And how do you use it in your practice? So, at the end of today, you're gonna be able to learn how to identify neuroinflammation versus neuroinflammation being primed or not primed, how severe it is, how to figure out the right dietary approach for them and how to support nutraceuticals. That's all today. That's the goal today. So, it's gonna be very clinical. And that is what we call part one and I call level one care. It's basic care. Level two care is part two, which is when you have to do a functional medicine approach. And you gotta go, "Do they have blood brain permeability? What are the things that are priming their glial cells? How do I work backwards? I know their glial cells are primed. But how do I figure the things that are still driving it?" And then we'll get into things like hypoxia and blood pressure and all the different things you see from the exam and how you have to
go deeper. Now we have a different spectrum of people. The first one we have over 810 people I think taking this course from all different fields. Some are neurologists, neuroscientists at prestigious universities. Some work at trauma centers that only treat brain. Some are just private practice practitioners like MDs, DCs. Some are nutritionists. So, some are practitioners suffering from their own brain injury or neuroinflammation. We have a whole spectrum of stuff. So, I'm gonna just try to get to the depth of all of it that I can. But you have to pick out what's right for you. And obviously, we can't cover every part of neuroinflammation. But the goal of this is to go through this material and do some follow-ups on our closed Facebook page and constantly answer questions and go over material and filter through this for this module and then dive into the next one, which is gonna be on GI and then go through that and go through questions and cases and go through that and then dive into the next one, which is autoimmunity. And those three, together, really give you a great picture of actually, the cases of neuroinflammation too and people that have neurological disorders. So, tomorrow, we'll really focus on the evaluation at a deeper level in part two. So, let's get into the goals. I have academic objectives and clinical objectives. The academic objectives today is just for you guys to make sure that you guys understand the function of glial cells, understand the concept of microglial priming, and learn the pathways that activate neuroinflammation. If you've gone through some of the Mastering Brain Chemistry course, you should be very familiar with it anyways. If you haven't, then we'll just quickly summarize those things. And you have all the material there for you. You also have a huge library of research papers. Those are there for you to dig into whatever you want. And we'll probably be posting more and more of them. I can't even tell you how many papers were screened to pick the ones that are there for you. There's an enormous amount of time to pick the ones that are actually good, that have a clinical relevance. Pretty much everything you'll see me reference in my PowerPoints, you guys will have the full paper with the exception of a few. But pretty much most of the papers. And then the keeping clinic lays out
which conditions you will see in a clinical practice, neuroinflammation. Understand the clinical position of mild, moderate, and severe inflammation. They're completely different. Have you guys ever had an old person that can't get out of bed, and they can't focus, they can't get motivated, they don't wanna do anything in life, and they just have no energy? That's a neuroinflammation case. That even is a severe neuroinflammation case. So, things like that. Those are the things you have to pick up on as a clinician. Let's go into a case. I just wanna show you some things first before we get all academic and all PowerPointed out. Let's watch a case. This is a case of a patient. This is a person who's speaking with his mom. And his mom has some cognitive decline. And neurodegenerative diseases are neuroinflammation. But they don't start – you don't go from no symptoms to dementia. You go through a transitional stage. There's different stages of it, stage one, stage two, stage three, all the way to stage seven. So, you gotta be able to pick up on the early stages of it. So, let's watch this.
[Video playing] Male Speaker: The son has asked his mother if he knows who his son is.
So, I wanna show you some of these because I want you to realize we'll show you a slide like this, and you'll see plaquing. And you go, "Oh, yeah. Plaquing. I know what that is." No. What you just saw in the video is what that is. So, the information we're presenting is – it's real life. If you know this stuff, you will help people. The stuff I'm gonna share with you will have a real clinical effect. You have to know it. You gotta study it. Look at the top part here though. Microglial. You see that neuroinflammation perspective there? It doesn't start with not remembering your child's name. It starts with, "I can't think. And I can't focus. And that's why I'm in your office. I have depression." Or their healthcare practitioner. "I'm getting tired. I can't work full days anymore. I can only see patients in the morning." "I can't think anymore. I gotta take notes. If I don't take notes, I won't remember anything anymore. I have to write everything down." That's where it starts. The brain is already inflamed. And if it's continuing to get worse, there's a problem. The person who had a
brain injury 10 years ago and is now sorting out symptoms, they're headed this way because the most common side effect of TBI is dementia. So, what you have to be as a clinician is to really remember the reality of the stuff. And the key thing is also, just from a neurology of learning mechanism, you can't actually activate your learning pathways until you first fire your limbic system. Your limbic system is your emotional brain. So, I'm trying to cheat and get your limbic system fired up. This information just doesn't become, "Oh, plaquings on a PowerPoint slide." That you really understand that these things are there. I'll show you another one.
[Video playing] Dr. Kharrazian: The mother. Is having a seizure. You got that mask. Her
inflammation got so bad, it led to a seizure, which is one of the things that happens with her inflammation. So, her daughter thinks this is normal. She's basically scared. She doesn't know what to do.
She's worried about how her daughter's gonna see her. So, one of the things you should know is when neuroinflammation gets severe enough, it can cause seizures. You'll see this with a lot of kids that have developmental disorders. You'll see people that have brain injuries when it gets pretty bad. And you have to understand – we're gonna talk about – there's definitely pharmacology critical acute phase inflammation. You need things to tide that inflammation. But as you go over the path of physiology and brain recovery, you can't put someone on prednisone forever because there are different pathways in the brain. The microglial have what's called an M2 pathway where you have to recover. When you put someone on steroids, you shut that down. There's no chance for recovery. It may be important from an acute phase. So, what's very troubling I think you guys are gonna see is you're gonna see like this, which is heartbreaking because you see a person who is scared that her inflammation - they don't know if diet impacts their physiology. They don't know what their lifestyle factors are. They've never been guided. They probably have gone to the most prestigious medical universities in the world, have gotten their diagnosis of MS. But they don't know what to do. It's all in the literature. I can give you guys hundreds of papers. We're gonna go over it.
You're gonna have a level of frustration that you're gonna go, "Why are people not incorporating what's been published? Why are there no strategies? How hard is it? What's the risk of changing their diet and lifestyle? What's the risk of putting someone on a cocktail of flavonoids that have been clearly shown in numerous studies to block brain inflammation? What's the big deal?" You understand? I think everyone will be a little frustrated when they see that. This is real. This is MS. Don't think MS is that slide that says MS on top. And then here, you can see – you can see here demyelination, this inflammatory response. This is a neuroinflammatory reaction. When we talk about neuroinflammation, these are the things we're talking about. We're not talking about just, "Oh, it's so fun. And glial cells. Woo-hoo. Flavonoids. Glial flavonoids. Yee-hee." It's not. It's serious stuff. It's people that are suffering. I'm gonna show you one more. This is the worst one. Sorry. But this is a kid with his brain on fire.
[Video playing] Dr. Kharrazian: Bedwetting is a brain-related disorder. It's not personality. People
who have brain inflammation many times, they… He's not acting. He's going through this.
He's not trying to get attention. So, one of the things you have to understand about the brain too is not only is 90 percent of the brain cells glial cells, but with the neurons that are there, the brain is 90 percent - most of the brain is there to inhibit the other 10 percent. So, not only are 90 percent of the brain cells glial cells and 10 percent are neurons, but the neurons you have, 90 percent of those pathways in the brain are there to inhibit the other 10 percent. What you have is an inhibitory system. And when people have neuroinflammation, the brain cannot function, do the things it can. It can't dampen the thalamus or the basal ganglia. It can't dampen proprioceptive input to the Purkinje cell inhibition system, to the deep cerebral nuclei. It can't dampen these different pathways. And when it can't dampen these pathways, you have a person who can't handle emotion, movement, sound, light, anything. And then these kids will have these relapsing, rebidding effects. They're fine. Their
brain gets inflamed. Their pathways don't work. They can't get their thalamus. They can't get their cerebellar inhibition pathways. And now they can't handle movement. And now they can't handle light. Now they can't handle anything. And people don't know what they are. So, they go, "This is psychiatric." It's not psychiatric. It's only psychiatric if you don't understand neurophysiology and neuroanatomy. It's not. It is physiological. And there are pathways involved with this. We can rebuild those pathways and we have them then do stuff. But you have to bring the neuroinflammation down. So, this is what we're after. Do you guys understand? Do you see that it's real-life stuff? So, please connect with what neuroinflammation really is. Neuroinflammation is the kid that's not getting better, can't focus in school, has developmental disorder. It's the person who had a brain injury years ago. Now they're starting to catch up with them. They may have even not even made that connection when they come see you. It's the person who is so depressed they don't know what to do anymore, may be even suicidal. Do you guys see about these athletes that have traumatic brain injuries? They kill themselves. They can't handle their sensory overload. They can't handle input. They have mood reactions. Their behavior's different. They don't know what to do. They have neuroinflammation. It's clearly established. But no one's doing anything for them. And steroids do not work because, again, they don't block the restorative pathways. They shut down the whole glial system. They blood brain permeability. They have these factors. There is no shortage of this. When I put together this first course, they go, "Neuroinflammation." I'm like, "I'm not sure if it's the right one because people are gonna hear the top and go, 'Well, I don't see that.' Or 'If they would have called it Dementia: Cognitive Decline, maybe I'd be interested.'" But no. Neuroinflammation. Now here's the other thing. It's inefficient as the clinician to learn treatments for every different condition that walks into your office. So, here's a different protocol for autism, a different protocol for dementia, a different protocol for brain injury, a different protocol – that means wow, that's the wrong way. You have to understand protocols for physiological pathways. You guys understand? Because if you understand the pathways for
neuroinflammation, you're gonna hit all these different conditions if that's the pathway involved. The chronically depressed person may need to have their neuroinflammatory models calmed down. The person who now has severe mood disorders and fatigue – now they think that chronic fatigue syndrome because the brain is fatiguing every time they try to do anything. They think they have a chronic virus or mercury when, in fact, all they have is brain inflammation. That's the person that you wanna pick up on. So, these are the real cases. Now there are some papers you guys can read about more about neuroinflammation on these children. But let me explain also something else. They don't just have subtle inflammation. The expression of the child you just saw suffering, he has glial cell priming. And so do most kids that suffer from things like autism. Now look at the title of this paper. "Neuroinflammation and Autism: Plausible Role of Maternal Inflammation, Dietary Omega, and Microbiota." But what did you see here? Maternal inflammation. You know what they're finding with child development disorders? The brains are inflamed. As a matter of fact, if they look at the structure of the child suffering with autism, they're able to look at the specimens of the actual brain tissue – maybe they passed away, and they were able to do some histology studies there. They see glial cells that are now primed. They completely change their shape. They have astrogliosis. Astrocytes going crazy. Blood brain become permeable. And then brain filled with inflammatory mediators. How did that happen? How did that happen at age 1, age 2, age 3? It's in the womb. It's maternal. You ever see patients and they have three kids that all have autism? You're looking at a mom with brain inflammation. You're looking at this environment. There's clear research now that shows infections during pregnancy dramatically increase the risk for autism. Infections turn on brain inflammation, especially in a vulnerable fetal brain. All these environmental triggers, if you – they found mothers live a mile from the freeway, there's increased risk for autism. The environmental triggers, the inflammatory triggers, they have an inflammatory role. I want you to picture this. You have a child that has their brain expressed into an inflammatory state during their neurodevelopment. Then they're born. Now let's say their
glial cells have already been primed. They've changed their shape. They're totally reacted to inflammation like an exaggerated state –
[Crosstalk] Dr. Kharrazian: Now they get a vaccination. Was it the vaccine or was it – you
triggered the neuro immune system. The immune system's already inflamed. And now you got a reaction. Does it make sense? I don't know. This is an area where people are still re – I don't have a stance on vaccines. I'm not going there. But I'm just gonna tell you what the research is showing. And part of the picture isn't that it's maybe the mercury. Part of the picture may be that it's the primed glial cell brain. And then you activate the immune system, and then that flares up. And certainly, we know one of the flaws with vaccination research so far is they have a subset – they haven't first stratified the study samples.
We don't know which groups are vulnerable yet. There's definitely a vulnerable group. We know who they are. When they do generalizable studies, we see no risk. So, then that's a whole debate thing which I don't wanna get into. But I just wanna just share with you that there are clear studies that show that children that have developmental disorders and especially autism have very inflamed brains. And their brain structures are different. And guess what else they find? That that glial cell priming lasts the rest of their life. So, the course information we're gonna talk about – if you guys are doing prenatal care, please do more than folic acid. I think we're past spina bifida these days. I think what we're facing is, "Is my child gonna have autism," as a real question for every parents nowadays, right? So, prenatal care is, "How do I make sure my kid doesn't have increased risk for developing autism?" because if any of you are gonna be parents or gonna have kids, that's a real issue. So, how is your brain inflammation? How's your patients brain inflammation? How do you find it? What do you do for it? What are the kind of things you're gonna look for? That's the stuff I wanna make sure we cover this weekend. Again, I'm just trying to let you know as an introduction how the stuff that we're gonna go into applies to your clinical practice. And what you have to understand about the brain is that you have these neurons that are firing. And they have to develop and
[inaudible] [00:30:24] So, white matter of the brain is still developing up until age 18 and 19. So, the brain's still developing once the child's born up until 18 and 19. Now white matter's branching up and moving different places. Synapses are happening. But the synapses have to be cleaned out. Neurons have to go on the right pathway. And what allows all that to happen are glial cells. So, glial cells, one of the things they do is they do what's called a synaptic pruning, like how you prune a tree, how a you clean up the debris of a tree. They go in there and clean up the synapses, so the synapses don't go to the wrong places, that they don't go into inefficient pathways. White matter has to move up the brain in different traction pathways throughout development. Glial cells make sure that that happens in the right direction. But glial cells can only do that when they're in an M0 state. M0 state means a steady state. When they get primed, they don't do that anymore. For how long? Forever. Now you don't get all your glial cells primed. So, you only get some of them primed. So, you have to work with what you got. But this is what I'm trying to explain to you is that there's a – it gets kinda scary when you look at these things. So, when you're looking at this pathway here, this is a chart. One of the papers you have. Timeline of major events occurring in the brain immune system and gut development, conception to adulthood. Look at neurogenesis, neuromigration. Neurogenesis, neuromigration totally depend upon healthy glial cell function not in a prime state, not in an activated, inflamed state. When I use the word primed, I mean overly active. Synaptic genesis. Astroglia cells help clean up the tissue. So, one of the things is it is impossible to recover from a brain injury. It is impossible to recover from or outgrow a developmental delay if the constantly inflamed. And it will not be as simple as getting him some probiotics that's really cool because they got the cool strain the rep told me and the fish oil. It's not that easy. It's a complex network. And the parents need to understand the physiology and the mechanism. They have to understand the lifestyle approaches and all those things. So, this is an important part of this too. So, here's an example of maternal inflammation. Mother has a pathogen. They have an inflammatory response. Inflammatory response primes the glial cells on the brain that's developing. The brain is now forever changed. Now they
have this inflammatory cascade. Their immune system is still developing. When does autism start to develop symptoms? Around 2-3 is when they start noticing some of it. And that's when the immune system gets more active and more developed so it actually can produce cytokines. And then when those cytokines start to get active and being able to be produced and the immune system is stronger, now they'll start to see the brain get inflamed. As their brain gets inflamed, they start to regress. This is the neuroinflammatory model of autism. There are many models of autism, but that's the neuroinflammatory model. So, here's another paper. "Maternal Immune Activation Implications for Neuropsychiatric Disorders." So, what they're finding is the health of the mom's inflammatory state, their systemic immune function, their gut function, these things have an impact on brain development in the fetus. And then kids are born with a brain. Now what degree of brain inflammation they have or glial cell priming they have has been set to some degree from pregnancy up until birth already. So, one thing you guys really wanna make sure you do from the information in this course is when you do any prenatal care, look at factors for neuroinflammation. What are they? I will teach them all to you that I know. And I'll share with you all the papers I could find on it, which I already have in your folders and stuff. And then how do you work backwards? And then hopefully, over the next few years, we keep finetuning it as new things come out. But it's a big factor. Okay. So, everybody okay with everything so far? So, you guys see brain inflammation is not just brain pain or headaches. Neuroinflammation is a devastating effect. And by the way, in this paper, what they did is they've done some studies where they look at prospective studies. And they can tell. If a mother had an infection while they were pregnant, the risk for that child to have bipolar disorder, schizophrenia, chronic depression in adulthood is dramatic. So, it sets up the stage. All right. Everybody good? Focused? Okay. So, now let's get into the material. Everything here was just to prep you, sauté you a little bit. Now the glial cells. Let's get into what you need to know. There are different types of glial cells. There's the astroglia, microglial, and oligodendrocytes. And this was a great paper. Did you guys remember to read this? "Glia:
More than Just Brain Goo." So, they used to think that these glial cells were just there to glue neurons together. The term glia being Latin for glue. And they didn't really understand the function of it. Now there's been several explosions. There's been a recent explosion with astrocytes. So, I'm gonna share you with some of that research too – that these glial cells aren't just immune cells, that these glial cells are actually involved with helping neurons actually function. And they have a major role in learning and memory as well. Now when you look at these cells, you look at these neurons and oligodendrocytes – this is a quick slide that summarizes them for you. Oligodendrocytes, they're the sheath around neurons. That's the majority of the neuroglia in the brain. We don't know much about what they do yet. All we know about them is they surround neurons and they help with increased nerve conduction. And they're the target sites for demyelination. We still get myelin-basic protein, myelin oligodendrocyte protein. You're looking at proteins on these oligodendrocytes, the sheath of neurons. Astrocytes are huge players, major breakthrough research coming out with astrocytes. Well, astrocytes maintain the blood brain barrier. Someone gets astrogliosis, that means these astrocytes gets inflamed. And there's blood brain permeability. We're gonna talk a lot about blood brain permeability part two. And then we'll go over a lot of the research here. But if these cells get activated, the blood brain barrier breaks down. And astroglia cells not only control the blood brain barrier. They're involved with synaptic function. They actually extend their arm right into the synaptic cleft. And they take away neurotransmitters that don't need to be there. They get blood flow to neurons. They help get oxygen and glucose to neurons. They have major roles in making neurons be able to do what they do. They're critical. They're not just immune cells. And then you have microglia which are the little cells that go in through your brain like little soldiers scavenging, making sure there's nothing there like little spiders checking things out. Here's another illustration of them made much more simple. And if you guys take a look at this diagram here, you guys can see Schwann cells. Schwann cells are just oligodendrocytes in the peripheral nervous system, in your peripheral nerves. Oligodendrocytes are the white
matter sheath in your central nervous system. That's the only difference. They're just white matter, myelin. And you got central and peripheral. Can my pointer back? So, Schwann cells. These are the myelin coating. These cells are live. They're glial cells in the peripheral nervous system like your peripheral nerves. Oligodendrocytes are like the white matter in your central nervous system. And then here you can see astrocytes. You see how they're surrounding the blood vessel? They're involved with the blood brain barrier. And microglial cells are scavenging around. Now astrocytes. I'll show you the control of the blood brain barrier. Let me explain something about these neuroglial cells too like astrocytes. 10 percent to 15 percent of the glial cells are astroglia cells. If you lose an astrocyte because they're vulnerable to oxidative damage and inflammation and stress, what do you think happens? Do you think it comes back? If you lose your liver cell or skin cell, it dies off, new one grows, right? Do you think that happens in the brain? No. There's no more cell division. What you lose, you lose. So, what you have to understand is if you have someone who's got significant brain inflammation for many, many years, and their astrocyte population – let's say it was at 15 percent of the brain – is now down at 12 percent or 11 percent, they're guaranteed to have chronic blood brain barrier permeability, neuroinflammatory diseases, and progression. There is a window of time you have to get this down. These cells are vulnerable to inflammation, oxidative stress. And over a period of time, you lose them just like as neurons go, you lose them too and you generate. You see MRIs. The volume size changes. Well, you lose the actual volume content of glial cells and astrocytes in the brain as well. There are some research that shows there's neurogenesis and these stem cells in the brain they just discovered that can grow. And there are some glial cells that are stem. And they can grow too. Just not enough to clinically matter. Good for headlines. But in real world, when you lose them, you lose them. So, the other key thing is these astroglia cells, they're not there forever. These cells, once they get into an inflammatory cascade, they can have some problems. And here, you can see the astroglia cell wrapped around the blood brain barrier. You can see the blood vessel there. So, these are critical for the blood brain barrier permeability.
And those are different than glial cells or oligodendrocytes. So, you always think of astrocytes. Think of blood brain barrier. Think of cells that help neuron function. Microglial cells think of scavengers. So, here's a culture of microglia. And they're labeled M. Astrocytes, A. And O, oligodendrocytes. And you actually will see the microglia move, scavenging. It's a healthy brain. Isn't that cool? These guys are in your brain, moving right now. Here's a really cool one. Watch this guy. This microglia's gonna pop in and pop out. Watch. Hello. Making sure there's no pathogens here. So, they're not only there to deal with pathogens, these glial cells, these Pac-Men. They're there to get rid of debris. So, when you look at all the neurodegenerative disorders today, they're called protein aggregation disorders, right? Alpha- synucleinopathy. Tauopathy. [Inaudible] [00:41:09] Normally, what the glial cells do is they chew them up and get rid of them. They scavenge around, see some dead neurons, dead cells, and they chew them up. But they can't do that if they're primed. When they get primed, they actually change their shape and have no more ramifications. These branches, they can't move anymore. They stay where they are, and they just eat up everything there like existing neurons. So, when your microglial cells also become primed, they stop scavenging, and they stop moving around dynamic like you're seeing them. And then there's a whole different scenario. So, this is the key phrase as we go over some microglial concepts. So, let's talk about microglial steady versus active state. Now on the left- hand side, you see what's called – they used to call these resting glia. They stopped using that term resting glia because they know they're always active and functioning. So, they just call them a steady state. And they call this M0 state, this one where you see the branches here. And these branches, just to make sure you understand some terminology, they call these ramified structure, ramified meaning branches. You see branches off the glia? See these branches here? Now you see these glia do not have branches? They're primed. That's the difference. That's how they look. They actually change from this ramified, branched-out structure to more of an ameboid structure with no more branches. The cell body is small here and gets large here and now turns into a macrophage ready to engulf. That's just the key thing. You guys see the word M1, M2? We'll
use those terms a lot. And we're gonna talk about everything dietary and nutrition lifestyle. So, turn down M1 and turn up M2 by the time we get done part one. Now M1 creates an inflammatory state. And M2 creates an anti-inflammatory state. M2 releases things like BDNF, IGF-1, growth factors. So, you can actually heal neurons, heal from a traumatic brain injury. M1 creates an inflamed response, which is not always bad because you have to get rid of tangles and plaques and amyloid and tau that's getting in the way of normal synapses. So, you need a little bit of both at some time. You need to have some degree of priming also at some time. It's just when the populations change dramatically. Now the glial cell in the ramified section here, this ramified version here on the left, that's called an M0, steady state. So, M0 is steady state. M1 is an inflammatory state. M2 is an anti- inflammatory state. They also call M0 a steady state, resting state, even though the term resting is not being used. M1, activation stage or inflammatory. We also call M2 deactivation or anti- inflammatory. So, the cases I just showed you, the three of them, they're here. They're activated. And probably, they're stuck in M1 because if they were getting their M2 pathway going, they would be recovering. So, when you see someone who's got significant brain inflammation, and they can't get out of it, and you see someone we classify as glial priming, what you need to know is their M1 cells are active like crazy, and their M2 cells are not working. That's the key concept. Now in a steady state, what neurons do is they're involved with a lot of key functions for neurons. And this is also why they're not – if you don't have lots of neurons in a steady state, you can't have proper neurodevelopment. If you don't have lots of neurons in a steady state, you can't develop proper plasticity as you learn and do things in your life. So, you can see here neurons here. And it says, "Developing CNS, wiring and pattering." So, it's showing you microglia. Now by looking at this microglia right away, can you tell if it's primed or not? It's not primed because you see the branches. You see the ramification structure. And these ramification structures, think of them as that's what allows them to also walk around, get around. That's not what they do. But it's an easy way to remember. Think of them like a spider. They can walk
around, get around. They can do things. Once they lose those little branches, they can't walk around anymore. They're no longer scavenging. They're eating up whatever's there. Now in a normal steady state, these are guiding vessel, sprouting of vessels. They're releasing neurotropic factors to help with plasticity. They're modulating how neurons grow and where they grow. And they help the synaptic pruning and make sure that these synapses are going to the right places. And they're just creating the right architecture for the brain because neurons don't do that. Neurons just signal electrochemical rating. That's it. Boom. And then in the adult, they're surveying. They're getting rid of plaques. So, they're critical in developmental stages, and they're critical for just normal function. So, they're not just there to fight infections. Don't think o glial cells as just there to fight infections. Glial cells aren't just there to chew up pathogens or the microglia. These glial cells are involved with proper, normal neuron functioning. Now here is an illustration of microglial activation from a ramified to an ameboid. Do you guys see that? So, I'm gonna show you a lot of slides this weekend. You can immediately tell if the slide is showing a primed glial cell or not by the structure of the glial. The glial has branches, it's in a steady state. If it doesn't have branches, then it's in the ameboid state. Now you see how some of these are partly there, in between? They use the term jellyfish many times. You see they still have cell body that's bigger, and they still have a few branches. They're kind of like a long jellyfish. That's not completely primed. They're still very active. They're still overzealous. And then when you get a lot of these glial cells in one area, it creates what's called a honeycomb pattern. So, you'll see the term honeycomb pattern with some of these things. Now we all have some of these just throughout life. But when you have a lot of these, your brain does not function well. And what you want is you want a lot of these glial cells moving around, scavenging, getting rid of debris, everything to be healthy. Now if you do get these primed glial cells, then you gotta make sure their M1 activity is suppressed and their M2 activity is up. So, that's what I was trying to tell you guys earlier. When you see patients, if they're glial cell primed patients, you're thinking of their case totally differently. If you find out that they
have a clinical history of glial priming or had a traumatic brain injury and never been the same, for example – because that's what happens with traumatic brain injury – then your goal, clinically is, "I gotta do everything with diet, nutrition, lifestyle and teach them how to stay in that state so their M1s never express as much as they are and their M2s get activated so they can heal and recover." Everybody with me so far? Now you see this transition from ramified to an ameboid or from a steady to a prime state? Think of it as a hardboiled egg. Will this ever go back to that? No. What if you use this cool supplement from the monks in Tibet? Doesn't do it. It's never been shown. They are trying. It does not change back. It's like if you get your limb cut off, will it ever come back? No. You can try to sew it and maybe put it together, but it's not gonna come back. That's the key thing. So, as the clinician, you have to know a primed glial patient is different than just subtle neuroinflammation. And your prognosis and your treatment outcomes are. Now let me explain something really important. There's a large subset of patients out there that are going from doctor to doctor to doctor to doctor for help. They get some things that help them, some things that don't, something to help them, some things that don’t because they are having these flare ups ups and downs. What's the most devastating for them is to completely have their spirit broken because when that happens to you, you can't trust anyone anymore because they see someone and go, "I think it's your gut microbiota. And I'm going to fix that." And maybe it helps for a little bit. And then something else primes your glia. "I think it's neurotoxins in your brain. We need to clear those out." And maybe that helps for a little bit. But they're reactivated by other factors. Do you understand that? So, they have a complete broken spirit. And guess what happens to practitioners who work with primed glial cells? They get broken too because they're like, "I just wanna help my patient. Man, I can't figure this out. What's going on?" Some of the patients that you may wholly burnt out with and you don't know what to do and focus on is because you've missed – you don't understand the prognosis of the mechanism. You may think, "Well, they're responding to my other patients. They're so weird. They're so different." They are different. Their brains are actually different now. And you have to sit down and figure out how to change your lifestyle and know there does gonna be some flareups
just like you treat an autoimmune disease patient. You treat them differently if you have a different prognosis. You try to get more good days than bad days. So, neuroinflammation has a different state and clinical prognosis when it's primed. Think of it as a hardboiled egg. I gotta show you this cool slide. Take a look at this. These are microglia. And what they do in this culture is they just let them float around. You'll see them swimming around and moving. That's what's happening in your brain right now which is really scary and creepy. And then they'll activate that the well, yes, which is an antigen. And then you'll see them change. Now you'll see, like here – see how they're moving around? See how they have their own little territory? They don't really step in each other's turf. See how they're moving around? None of them are too large. These guys here may be a little bit large. You see that? Could be this guy here's primed. You see how it doesn't have any branches anymore? So, those are a couple primed cells. These are normal glia. So, we'll have a little bit of priming here and there from different things in our lives, a little fall you had when you were six, for a little small area. But the majority of your neurons are still ramified. It's not really that big of an issue. Now take a look at this. What are you seeing with these cells? This is within a few minutes here. They're starting to turn into a primed cell. These branches are going away. Now they're getting an ameboid structure. You see these prime cells here, totally different than here. That's with LPS. By the way, LPS is what you have at high levels when you have intestinal permeability. LPS crosses the blood brain barrier from bacteria and shreds on glial cells. I just showed that in a specimen. And then here's the illustration. Here's this neuron on and off signal controls microglia. And you have to have the ability to turn these off. And it becomes detrimental when you can't turn these off anymore. That's the key thing there. So, you want neurons in a steady state. That's the goal. But not everyone has neurons in a steady state. Key concept. When microglia become activated, they shift their function from supporting neuron and synapse homeostasis then to an immune cell involved solely with the protection of the brain, like a hardboiled egg. So, here you see a nice illustration of this. Neuron glial cells, they're just happy, doing their thing, controlling homeostasis,
getting blood flow to neurons, getting rid of plaques and debris, making sure branches are going the right way. Everything's great. They're resting. M0. Then they get primed. You guys see that? They change their shape. They lost their branches. They get this ameboid structure. They're never going back to that. Now remember, this is happening in populations throughout the brain. It's not the whole brain all at once depending on this area. For example, if you had traumatic brain injury to your frontal lobe, you may just have your frontal lobe primed. If you had a systemic infection, you may get global infection throughout. But you still have enough healthy resting ramified neurons where you don't see any clinical symptoms. So, just be aware of – it's not all or none. There are populations of this depending on the severity and the impact or the direction of them. So, there's another concept, which is called reactivation of primed glial cells. So, let me explain what that is. And it's how you start to diagnose patients that have primed glial cells. If you see a patient that'll eat a food protein – let's say they're sensitive to gluten. Patients don't have the same response, right? Some will eat it, and some will be in bed for weeks and can't get out of bed and have severe depression, and it completely changes them. That's different than someone else. Same protein that the other person got exposed to. That's a primed glial cell. Somebody has a stress response, and they're stressed. Someone has a stress response, and their cognitive decline goes down. Their mood completely changes. They can't get out of bed. They can't focus anymore. They sleep for 10 hours now. That's a primed glial cell. So, you get exaggerated responses to triggers when the glial cells are primed because these cells, once they become primed, they're gonna have a significant output of inflammatory mediators, and they're gonna shut down the brain very, very quickly and very, very aggressively once they're primed. And the way you clinically find priming is you see how different insults then change their clinical presentation. I will go into those. And I'm gonna break and down and make charts for you. I wrote them all out. I made it as linear as I can make it. And you can go through a whole process of doing it. So, this is the concept of microglial priming. You have the glial cell. It starts to change shape. They become primed. And then they get the second hit. And that second hit is gonna
cause loss of significant brain function, which for some people will be depression. For some people, it will be motivation. For some people, it'll be hard neurological science. They'll start to have numbness in their face, and they can't walk. But it's gonna be significant. And then it goes away. And then it comes back. And then it goes away, and it comes back. And what do you think's gonna happen when they do an MRI over their brain? It's gonna look normal. You don't see glial priming. You know where you see glial priming? Post-mortem. Brain tissue slices. You don't see it on imaging studies. There are some advanced imaging studies I'll share with you guys on part two where they can look at this for research studies but not in a clinical where you send them out to get an MRI. They're not available for clinical. They're only available for research models. Now hang on one second. Hang on one sec. So, by the way, the only way I can make this flow with so many people streaming in and doing this is I can't take questions during the presentations. So, at the end, if you have questions, we have a link that sends you out to go through. And just send those in. At the end of the day, we'll cover all the questions. And then we'll also cover questions on Facebook page. And if you guys are here, we can catch my break and go over questions. But let's not do it during the presentation. Okay. Now remember this pathway four mechanisms that impact brain inflammation? So, let's talk about this. So, we know the brain can get inflamed. We know the brain can get primed. When a brain gets primed, we know that it's different. And we know once the brain is primed, other triggers that come in completely shut down the brain. That's the basic concept so far. So, how does the brain get inflamed? So, these are the four pathways. This was in your preconference material. So, we know that the brain has the ability to be inflamed with – this is all with an intact blood brain barrier, meaning the blood brain barrier's still healthy. So, there are four pathways to activate the brain when the blood brain barrier's healthy. One of the most common presentations in elderly patients of glial priming is they get an infection. The most common ones are lung or bladder infection. And they get delirium. And when that happens, they've done some research where they studied their blood brain barrier, and the blood brain barrier's still intact. So, you don't have to have your blood brain barrier be permeable to have an inflammatory
response in the brain. However, if it is permeable, you're in trouble. We're gonna show you how to do testing for blood brain barrier permeability and how to use that in your own practice. If you guys see a person's blood brain barrier permeable, you should literally drop your pen or your pencil and just freak out for a second and go, "Oh, my gosh. This is so scary," because that's – you would never do that with a leaky gut. You do that with a blood brain permeability, it's a whole different scenario. It's no joke. And they're not always easy to restore. I'll show you some case examples. They're serious. Now when you guys are looking at this, one pathway is a diffusion pathway. So, in a healthy blood brain barrier right over the hypothalamic regions – this is called a circumventricular. It's around the ventricles. It's right where the hypothalamus sits. The blood brain barrier's a little bit more permeable for different cytokines because your hypothalamus is involved in your neuroendocrine immune response. So, we have certain areas of the blood brain barrier normally permeable to activate the hypothalamic pituitary endocrine response, the neuroendocrine immune response. They call that neurogenic inflammatory response. That's a normal part of a healthy blood brain barrier. So, we don't have to have breach to trigger a neuroinflammatory response just because of the way the blood brain barrier is around the hypothalamic regions. The inflammatory side has the body activated. We also know that we have pathways from the vagus. Do you guys remember anatomy, the vagal pathway, the vagal nerve? It starts in the brains then goes all the way to the gut into the liver, into the organs, and then all the way back. It's bidirectional. Inflammation in the liver, those cytokines, inflammatory cytokines in liver, things even specifically – some studies have shown CRP that's produced in the liver. They go up the vagal nerve and turn on brain inflammation. If you guys see high CRP, you have a pathway from the vagus turning down brain inflammation. We'll go over some of this research in part two because I'm gonna show you guys step by step if you had a patient with vagal priming, what are you gonna do with labs? What are you gonna look for? How you gonna monitor them? How you gonna check through? So, I'll show you the study
with the clinical application. All right. Now the other key thing is the vagus comes in the gut. So, gut inflammation can immediately, directly up the vagus inflammatory cytokines LPS. Remember that culture I showed you of LPS activating glia? LPS signals cytokines, neuropeptides. Can all crawl up the vagus in a anatomical pathway and then turn on brain inflammation with an intact blood brain barrier. So, liver and gut inflammation turns on brain inflammation. And then transport. So, the blood brain barrier also has active transport. They're learning about these, that some inflammatory cytokines can actually cross the blood brain barrier through natural transfer pathways. Still a new area of research. There's not a lot of information about that yet, but they know it's there. And then the other key thing is the vascular endothelium, the blood vessel between the blood brain barrier, in a sense – the vascular endothelium, as you guys know, is not considered an endocrine gland because it produces hormones. It has receptors and signaling. That's not just a pipe. It's dynamic. So, inflammatory signals bind to endothelium receptors. And those endothelium receptors activate astroglia branches. And astroglia cells then turn inflammatory responses in the brain. So, the bottom line is this. Inflammatory mediators and circulation in the blood can turn on glial cells. Then astrocytes can turn on brain inflammation, gut inflammation, liver inflammation. They can turn on brain inflammation. And then you just normally – a cytokine response can activate that neuroinflammatory response. Now here's a key thing about the brain. The brain doesn't have a very good antioxidant system. You know who makes antioxidants in the brain? Microglial. Guess what? They get depleted with chronic inflammation. So, once they can't deal with the inflammation, then neurons are next to go. They can't quench that oxidative stress. Neurons then start to branch off and die off. So, we'll talk about how nutraceuticals and antioxidants that have been published in studies are so critical when we deal with neuroinflammation or even just prevention. So, they don't get worse and so forth. So, this is a summary of those four pathways. This is in your pre-course review. And then here's the picture of blood brain permeability. This is completely another gamechanger. Let me give you a really terrible scenario:
primed glial cells and blood brain permeability. That's devastating. And then the next level would be primed glial cells, blood brain permeability. It's now turned on neurological autoimmunity, adding antibodies to myelin and alpha beta tubulin and MOG and MBT and these other things. We'll talk about that too. And that's a whole different scenario. Okay. So, let me show you some glial cells and more of this inflammation. So, you guys see the big picture so far? I'm hoping I'm making this clinical for you. It's not just a bunch of academic stuff that you kinda see how they come in. But this is the intro. So, I have to make sure you understand priming and so forth. So, let me recap and then start again. I like to do – what do you call it? – reviews throughout. Is that okay with everyone? Because I have a vision of what you need to be at the end of part two. And all I'm struggling the whole time is to get you there. So, what you have to know now is that no one's gonna come into your office telling you that they have neuroinflammation. No one's gonna tell you in your office they have primed glia. You have to figure it out from the clinical conditions that they come in with. The key thing is just to know the most common ones. A person that had a traumatic brain injury that was never the same. You can guarantee there's glial priming. Where? It's not gonna be the whole brain. It's probably gonna be a focal area. What if it's their speech area? What if they damaged the Broca's area? They'll tell you, "When I eat certain foods, I can't talk. I slur my words." You're like, "Oh, then you got primed glial cell, probably in your Broca's area. Left side. Let's fix it." Someone else comes in and goes – I'll give you an example. Ten different examples. "Oh, whenever I get exposed to gluten, I see floaters." "Great. Area No. 18-19 occipital lobe. That's primed. Did you hit the back of your head?" "When I eat certain foods, I can't move – my right arm gets heavy." "Great. It's your left premotor strip if it's your right arm." So, you can actually figure out exactly where they are if you know your history. I'm gonna give you a questionnaire form to do that for you so you don't have to spend 20 years doing neurology. You can just know where the symptoms are. And then you can find focal glial priming. So, when people have priming, they don't tell you what their symptoms are.
And they're gonna be the weird patients that had a brain injury. Now they have new symptoms. When something new comes in, the second assault. So, remember, glial cells have a steady state. Then they can become primed. Once they become primed, they're forever changed like a hardboiled egg. Once they get primed, the second hit that happens throughout – remember, it hits after that. Refer to the second hits are the ones that really then present clinical symptoms. And then you have different pathways to the brain that cause inflammation. And then the worst scenario is if the blood brain barrier is permeable. Good? Now take that all information. Put it right here. I'm gonna tell you some cool stuff about astroglia cells. Now why is this important? Because when you're also dealing with a neuroinflamed brain, you have to realize that cognition and memory are not gonna work well. As a basic concept, when there's brain inflammation, things happen to neurons besides dying. In subtle degrees of inflammation, No. 1, nerve conduction goes down. The speed. So, when the speed of neurons firing goes down, people get slowed cognitive activity. They call it brain fog. They can't get to their thought. They're trying to find where their shoes are. Normally, they can think about it right away. Now it takes them a long time to figure out where their shoes are. They can't get to their words. It's reduced nerve conductance. That's a consequence of inflammation impacting neurons. Neurons slow down nerve conduction. Inflammation also has a dramatic impact in astrogliacytes. And astroglia have been shown to directly impact how all your neurons work, especially learning and cognition. So, this is a great paper, "Glial Biology and Learning and Cognition." You see the astrocyte down here? And the astrocyte is modulating the neuron synaptic cleft. So, astrocytes impact the neuron synaptic cleft. They can't do it in an inflamed state. When they're not inflamed, they can do their job. And they get rid of neurotransmitter substances in the synaptic cleft. And they help get blood flow to neurons. And they help get oxygen to neurons. And they help this whole practice work. They clear out glutamate [inaudible] [01:06:47] pathway in the synaptic cleft. They're critical factors there. And we know that when glial cells – well, they also help the hippocampus, the cognitive recall area of your brain along with memory connect and function properly. And most of the studies they've done with it so far. Now
this is where we get into Einstein's brain. Do you guys know this story? I did a little video, talked about it a little bit. When Einstein died, he was at Princeton. He had a position there at Princeton. And apparently, he just didn't talk to anyone and just thought all the time and was in his own world and just coming up with thoughts no one could understand and very frustrated. Anyways, he was a brilliant guy. So, when he passed away, the pathologist there took his brain without approval from the family. Just took it. So, they did a biopsy to find his cause of death. And the pathologist stole Einstein's brain and put it in a jar because he thought, "How his brain functions is different than any other human we've ever known because he's come up with discoveries no one can even imagine. And we have a duty as researchers to study his brain." So, this pathologist stole the brain. And then like most things happen, the wife brought sense into the husband, and the pathologist listened to his wife and said, "I stole the brain. I'm sorry." And then the family is like, "Fine. You stole the brain. Okay. But that wasn’t the right thing to do." And anyways, they started studying his brain. And they wanted to see if Einstein's brain was any different. And guess what? It wasn't. The same amount of neurons, same type of atrophy except one thing. He had way more astroglia cells. A lot more than any other brain. So, his astroglia cell numbers were profoundly high. So, we have 10 percent to 15 percent. I'm not sure the exact numbers, but he had percentages way above statistical significance there. And so, his brain was actually different. At the time, they didn't care because they didn't know what astroglia cells did because they just thought it was a glue that kept neurons together. So, all they were doing is focusing on neurons. Go, "Yup. Same amount of neurons." But remember, a mice has 65 percent glial cells. We have 90 percent. And a worm had 25 percent glial cells. So, glial cells are also not just immune. They help with neuron function. So, his glial cells, especially in his learning memory areas, his cognition areas were much, much higher. And that's one of the things they found out with it. Now Salk did some interesting study. Let me show you this great video. Watch this.
[Video playing] Dr. Kharrazian: Okay. So, here's the key thing. What they're learning now in the
world of neuroscience is a major, major breakthrough. First
breakthrough was that glial cells are not just glue cells. Then like, "Oh, these glial cells, they scavenge things." Now the big breakthrough is these astroglia cells are involved with making neurons actually work. Now it's not just looking for a pathway. It's the whole brain. But they're doing a lot of research now with learning and recall and so forth because there's a strong concern to do research with dementia and a lot of funding right now to do research for dementia because it's impacting so many people. But remember this. You only have an X amount of astrocytes.
With chronic inflammation, they die off. This is unrelated to the concept of plasticity. What's plasticity? Plasticity isn't about glial cells. Plasticity is about a neuron. A neuron gets activated. It branches over and attaches to another neuron to get the pathway and function back. It's all it is is branching into each other. That's plasticity. Astrogliacytes aren't related to plasticity. They allow just neurons to function the way they do. So, one of the scariest concerns for long-term neuroinflammation is the loss of your astrocyte populations. And once they go, they go. And once they go, the person's never the same. So, you have to be realistic as the clinician too. If you see someone in stage four dementia, it's not realistic to think you're gonna get them into stage t wo. You know what I mean? You can get some of the cognitive symptoms to change for a while, but that's not changing their brain anatomy. That's just getting some plasticity and some functions there. Now another major area of big research is the gut which is also important because they find gut messenger pathways directly activate astrocytes. Another huge kapoo. What? Brain gut access. We all know. There's decade of brain, which ended up being 30 years. Now it's like the decade of the brain gut access, which it's already past a decade. But those are the things that are there. And then by the way, when I found this out, I'm like, "What was his diet? What was Einstein's diet?" because the research is also showing the more diverse the gut is, the less inflammation you have in the gut and also, potentially in the brain. So, the more microvolume diversity a person has, the less inflammation they have because they turn on T-REx cells. So, microvolume diversity activates the production of short chain fatty acids. Then short chain fatty acids turn on T-REx cells. And T-REx cells reduce inflammation in the brain, itself. I'll show you some studies on
that. And also in the gut. So, my question was, "Well, what was Einstein's diet?" Well, he was a vegetarian but at the end of his life, not in the beginning. And the only thing I could find about him was that he was a vegetarian. But he probably ate the classic German diet, lots of fermented food and all these things. But I think it's a combination of things too, the astroglia cells plus the amounts of inflammation. All these pathways are a really key thing to make a difference for you. So, anyways, the bottom line is that neuroinflammation has long-term effects. And it's linked to these other pathways. And we're still learning about them. But we do know – even though we don't know all the details of how astrocytes function, we do know one thing. We do know as you get chronic inflammation, you do lose them. And then once you lose them, your brain will never be the same. We also know that when glial cells become primed, the brain changes. And once the brain changes, you have a primed pattern. Now I'm not saying all this stuff to you to depress you. I remember I spoke to a friend of mine. He goes, "I hate hearing you talk. You always get me so depressed." And I go, "That's not my objective. The goal isn't to make anyone depressed. The goal is to have a real clinical scenario so two things happen: You create a realistic model for your patient, so they stop having their spirit broken, and you find ways to deal with that. And you, as a clinician, don't have your spirit broken dealing with cases you think are like other cases." That makes sense? So, you have to have a realistic prognosis to make it. If you guys are here, I can tell you this. You're an awesome clinician because you're taking the time it takes to learn. There are a lot of clinicians here like, "If I don't need it for my hours, I'm not going. I don't care." They don't wanna learn anymore. So, the fact that you're here, you're obviously here, and you wanna help patients. Then you're above the average. So, we have to make sure that we don't burn ourselves out because there's not many of us out there. And you have to understand proper prognosis. So, understand priming. Understand astrocytes and how they function and the lifespan that they have. Last key thing in this next 12 minutes here, which I wanna make sure that you guys understand, which is understanding mild, moderate, and severe
neuroinflammation in clinical presentation. This is clinical now. So, we talked about some fun stuff. Now we're going back to clinical stuff. So, remember, when glial cells turn on, they can be primed. And there are different pathways to turn on glial cells: the liver, the gut, the blood vessel, endothelium, and even breached blood brain barriers can turn on brain inflammation. And remember, when the gut gets inflamed, you see neuro conduction slow down. So, I wanna show you this video. Here's what you're gonna see. You're gonna see a neuron sending an electron signal to another neuron. Synapse potential. You're gonna see normal speed. And then you're gonna see brain inflammation speed. Normal speed. Brain inflammation speed. And you'll see it four times, so you can see it. All right? It's a illustration. It's not a real neuron. But just so you can understand the concept. Normal speed. Slower. Normal speed. Slower. All right. So, subtle symptoms of neuroinflammation. No. 1 is a brain fog. And patients will actually come in and tell you they have brain fog. Hazy thought. Can't recall. That's a reduction in nerve conduction speed. Is that glial priming? No. That's just inflammation. That can go away. You can totally change that clinically with some clinical variables. So, that's nice to see if it's just that. Now the key thing that's also – it comes and goes. Notice a little variation in mental speed. The other key thing you'll see is reduced brain endurance. So, what does that mean? Well, let me explain a few things. You have neurons that function. And they have mitochondria. And you have all this glia around them. When the glia get activated and they're producing inflammatory mediators, these inflammatory mediators uncouple the mitochondria. We're gonna talk about that a lot more later. When they uncouple the mitochondria, there is not enough ATP for neurons to do what they normally do. And when neurons lose their ATP from inflammation caused by glia to mitochondria neurons, the neurons endurance goes down, so they can't handle – they can still do things. They just can't do them as long as they used to. They can still drive. But there's no way they can drive for two hours anymore without having to sit down, take a break. They can still read. But they can't go through a whole chapter. They have to take a break. They can still do tasks like they used to. They just fatigue out. That's an endurance issue.
And that's different than loss of function. Loss of function means, "I can't drive anymore. Every time I try, I get dizzy." That's more progressed, right? So, in subtle neuroinflammation, you don't lose function, necessarily. You lose endurance. You can still do the things you normally do. They may be slower. They may be a little bit hazier. But you haven't lost function yet. These are great to work with. Don't worry about glial cells being primed. You're like, "Yay. We can do some things. Rainbows might come out. Birds may be singing." The other key thing is they may have brain fatigue after exposure to specific chemicals, scents, and pollutants. You gotta be very careful to make sure it's not priming because that's a key feature of priming. With priming, they lose total function. They're totally compromised. And brain fatigue exposure to foods. So, let me give you an example. Subtle neuroinflammation. Let's say I have sensitivity to dairy proteins. Gluten, dairy. Most common, right? So, I eat something with milk and dairy in it. And then I go, "Oh, I get brain fog. I can't think and focus as well. All right." And then maybe I'll take some anti- inflammatories. I would take Tylenol. Maybe I'll take fish oils. Whatever. And then it goes away. And then I'm like, "Okay. Great." That's subtle neuroinflammation compared to, "I'm gonna take this. And now I can't function. And the room is spinning. And I'm dizzy. And now I'm gonna throw up." That's completely a different degree. So, the second example is primed. So, if they, let's say, for example, injured their cerebellum, and their cerebellum cells are primed, they get an inflammatory trigger. Now they're getting vertigo and spinning. It's not just that they've lost some endurance. So, when you see loss of neurological function, completely like that, you're worried about a primed cell, glial priming. It's no longer subtle. When you just see some slowness, some lack of endurance, that's subtle neuroinflammation. Pretty straightforward, right? So, that's the key thing. Do they have subtle neuroinflammation? You're not as worried about these subtle neuroinflammation patterns. Moderate. This is now a whole different scenario. And this is termed in the literature sickness behavior syndrome. And with sickness behavior syndrome, now a person doesn't just get brain fog and a little bit of slower brain endurance, they get depression, like chronic depression. They can't get out of it. They can't concentrate for any long periods of time.
They have sleepiness. They need excessive amounts of hours of sleep to function. They get severe fatigue. They have no motivation. They don't have an appetite. They can't be physically active. They're just in bed. You ever had any of these, like this exact scenario? That's caused by sickness behavior syndrome. It's moderate inflammation of the brain. If I think of it as – it's a significant amount of inflammation. Just classify it as moderate. Severe is like seizure, coma, like the second video I showed you where the mother that had MS started going into a seizure from the inflammatory to reach cascade. You're probably not gonna, in a clinical setting, see a lot of patients that have this degree of inflammation where they're getting into seizures and comas and are now into your office for functional medicine, nutritional workup. You might eventually have them come in your office. But you're very likely to see subtle. And you're very likely to see moderate. Now whenever you see subtle or moderate neuroinflammation, you still have to ask the question, "Are they primed?" And the way you would know if they're primed is if they have an insult that makes them significantly lose function. They have a stress response. And now they have sickness behavior syndrome. Listen. For example, I don't know. Something happens. You get in a car accident. "Oh, no. Sorry. Here's my insurance card. That sucked." Person gets in a car accident. Now they're in bed for a week. "I can't get out." That's primed. That's sickness behavior syndrome. So, there's a little bit of overlap between these, as you can see. Now realize this too as a clinical key point. The area where the priming is is gonna cau – the area of the brain where the glial cell priming is is gonna cause unique symptoms. They're not all gonna be the same. Depends on what region of the brain is no longer firing or now shut down because of the priming glial cells turning off neurons and shutting down mitochondria. So, if it's the frontal lobe, it'll be focus, attention, concentration. If it's the medial temporal lobe, it'll be memory and recall. If it's the occipital lobe, it'll be floaters and visual pathways. If it's the cerebellum, it'll be dizziness and balance. So, these patients are classified as weird. "What do you mean when this happens to you, you get – what do you mean when you smell gasoline fumes you wanna vomit and see different colors in your
visual field? That's not real. Go to psychiatry. You're crazy." So, we'll go through each of those pathways as well. Okay. So, here's the chart I made for you. Subtle, moderate, and severe. You can go through each of these different cascades. Just a summary of everything on one page for you. You guys will notice the key diagrams I put in a separate section in your materials. It's just diagrams. You can just download those, the ones that can just quickly reviewing materials that's in there. I wanna read those to you. Let's go over some key examples to help put this together. So, here's a scenario. Jack is a 42-year-old male who suffers from chronic depression. He has tried every major category of anti-depressants. But nothing has worked. He feels like he needs to sleep nine hours a day just to function. Some days, he just cannot get motivated to do anything. What do you think? Serotonin? Dopamine? Adrenal exhaustion? No. This is modera

Kharrazian Institute – Neuroinflammation, Course One ...

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