Brain Dysfunction

Department of pathophysiology, Tongji medical college, HUST

Introduction

Structural Characteristics It is located inside the skull, protects brai

n from injury, confines the brain It is composed of neurons and glial cells The blood supply is from twin vertebral a

rteries and carotis interna The brain blood barrier protects brain fr

om invasion of toxic insults

View the Brain

Cellular composition

NeuronGlia

Structure of Neuron

Cellular Functions

Neuron is in charge of different functions

Glia nourishes and protects the neurons

Characteristics of Metabolism The most active organ in energy

metabolism Glucose is almost the only source of

brain energy The storage of glucose in the brain is

very limited

Characteristics of Brain Diseases

Region-dependent consequences to injuries Limited capacity for self repair Acute brain damages will cause

disturbance in consciousness whereas chronic lesions usually lead to cognitive dysfunction

Cognition

The ability of the brain to process and store information in order to solve problems. It involves a series of voluntary psychological and social behaviors, such as study, memory, language, thinking, emotion etc.

Structural Basis of Cognition

Lateral (A) and medial surface (B) of brain

Cognitive Disorder

The disturbance of the mental process

related to learning and memory, reasonin

g and judgment, accompanied by aphasia,

apraxia, agonasia or disturbance in exec

utive functioning

Major Manifestations Learning and memory disorders Aphasia Agonosia Apraxia Dementia

Cognitive Disorders

Etiology and Pathogenesis

Chronic brain damage Chronic systemic diseases Mental and psychic disorders Other factors

Chronic Brain Damage Imbalance of regulating molecules in

the brain Protein aggregation in the brain Chronic cerebral ischemic injury Environmental and metabolic toxins Cerebral trauma Brain aging

Imbalance of Regulating Molecules

Dopamine Norepinephrine Acetylcholine (Ach) Glutamate Aberrant neuropeptide Lack of neurotrophic factors

Dopamine Pathway

DopamineDopamine

DopamineDopamine

Parkinson DiseaseParkinson Disease ((Cerebral trauma? ))

NorepinephrineNorepinephrine

GlutamateGlutamate

Protein Aggregation in The Brain

Gene mutations

Abnormal post-translational modifi

cation

Infection of slow virus in the brain

Lewy bodies(accumulation of synuclein in PD)

Stained by haematoxylin/eosin,

and by synuclein,

Composed of a dense granular core and a halo of radiating filaments by EM

Alzheimer Disease

Alzheimer’s Disease Alzheimer’s Disease

Gradual memory loss Decline in the ability to

perform routine tasks Disorientation Difficulty in learning Loss of language skills Impairment of

judgment and planning Personality changes

Accumulation of tau and Ain AD

Senile plaques: A

Neurofibrillary tangles: P-tau

PHF and NFT by EM

Normaltau

AD p-tau SerThr

pp

p

p

p

p

p

p

ADPATP

p

p

Protein kinases ?

Protein phosphatases

Imbalanced phosphorylation system leads to Imbalanced phosphorylation system leads to tau hyperphosphorylationtau hyperphosphorylation

SerThr

Pi

a b

d c

Morris water maze test from Control and model rats

Mad cow disease(accumulation

of prion)

Chronic Cerebral Ischemic Injury Energy exhaustion and acidosis Intracellular calcium overload Free radical injury Excitatory toxicity Inflammatory reaction by cytokine

GlutamateGlutamate

Chronic Brain Damage

Imbalance of regulating molecules in the brain

Protein aggregation in the brain Chronic cerebral ischemic injury Environmental and metabolic toxins Cerebral trauma Brain aging

Pathogenesis of Cognition Disorder

Principles for Treatment of Cognitive Disorders

General neuroprotective treatments

Maintenance of normal neurotransmitte

r level

Surgery

Consciousness Disorder

Consciousness is denoted in brief as

the sense of awareness of self and the

environment. It consists of two aspects: state

of arousal and content of consciousness.

Consciousness disorder is defined a

s parenchymal mental disorders in whic

h there is impairment of the ability to ma

intain awareness of self and environmen

t and to respond to environmental stimul

i.

Structural Basis for Consciousness

Dysfunction of brain stem reticular

formation

Dysfunction of thalamus

Dysfunction of cerebral cortex

Structural Basis for Consciousness

Major Manifestations

DeliriumDelirium

Confusion

Drowsiness

Coma

Etiology and Pathogenesis

Acute brain injury

eg. diffuse encephalic infection, diffuse brain

trauma, subarachnoid hemorrhage,etc.

Acute brain intoxication

Acute Brain Intoxication Endogenous toxins injury

Alteration in neurotransmitter

Aberrant energy metabolism

Nerve cell membrane injury Exogenous toxins injury Intracranial extrusion and

destructive lesion

GABA released by one cell either binds to another cell or be reabsorbed

Enough GABA binding to the other cells prevents over excitation in the brain.

GABITRIL increases the level of GABA by blocking its reabsorption

This blocking helps make more GABA available for binding to the other cells

Etiology and Pathogenesis of Consciousness Disturbance

Systemic Disturbance

Respiratory disorders Disturbance of fluid-electrolyte and

acid-base balance Circulation dysfunction Others

Principles of Prevention and Therapy Urgent management Making a definite diagnosis as soon as

possible Monitoring vital signs and

consciousness state Brain protections

Production & release of dopamine