Brain Dysfunction Department of pathophysiology, Tongji medical college, HUST

Introduction

Structural Characteristics It is located inside the skull, protects brain from injury, confines the brain It is composed of neurons and glial cells The blood supply is from twin vertebral arteries and carotis interna The brain blood barrier protects brain from invasion of toxic insults

View the Brain

Cellular composition Neuron Glia

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, reasoning and judgment, accompanied by aphasia, apraxia, agonasia or disturbance in executive 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 Dopamine

Dopamine

Parkinson Disease () ( Cerebral trauma? )

Norepinephrine

Glutamate

Protein Aggregation in The Brain Gene mutations Abnormal post-translational modification 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 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 A  in AD Senile plaques: A  Neurofibrillary tangles: P-tau

PHF and NFT by EM

Normal tau AD p-tau Ser Thr pp p p p p p p ADPATP p p Protein kinases  ? Protein phosphatases  Imbalanced phosphorylation system leads to tau hyperphosphorylation Ser Thr 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

Glutamate

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 neurotransmitter 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 as parenchymal mental disorders in which there is impairment of the ability to maintain awareness of self and environment and to respond to environmental stimuli.

Structural Basis for Consciousness Dysfunction of brain stem reticular formation Dysfunction of thalamus Dysfunction of cerebral cortex

Structural Basis for Consciousness

Major Manifestations Delirium 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