BRAIN DAMAGE AND HUMAN NEUROPSYCHOLOGICAL DISEASES

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BRAIN DAMAGE ANDHUMAN NEUROPSYCHOLOGICAL DISEASES

• Outline
• 1. Causes of Brain Damage
• a. Tumors
• b. Cerebrovascular Disorders
• c. Closed-Head Injuries
• d. Infections
• e. Neurotoxins
• 2. Neuropsychological Diseases
• a. Epilepsy
• Kindling Model of Epilepsy
• b. Alzheimers Disease
• Transgenic Mouse Model of Alzheimers Disease
• c. Parkinsons Disease
• MPTP Model of Parkinson's Disease

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Causes of Brain Damage

• Tumors
• A tumor (neoplasm) is a group of cells growing
  independently of the rest of the body
• a tumor can be
• Encapsulated (grow within their own membrane)
• usually benign (can be removed without further
  risk of growth)
• Infiltrating (grow diffusely through surrounding
  tissue)
• Usually malignant (difficult to remove or destroy
  and likely to spread)
• Metastatic tumors are tumors that originate in
  one organ and spread to another
• the symptoms of multiple cerebral tumors are
  often the first signs of lung cancer
• 20 of brain tumors are meningiomas that grow in
  the meninges
• they are encapsulated and benign

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Cerebrovascular Disorders

• Stroke" is commonly used to refer to any
  cerebrovascular disorder of sudden onset
• Two types
• 1) cerebral hemorrhage
• the bursting of aneurysms (balloon-like dilations
  of weak areas of blood vessels) is a major cause
  of intracerebral bleeding
• aneurysms can be congenital or the result of
  infection, toxins etc.

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Cerebrovascular Disorders

• 2) Cerebral ischemia is a disruption of blood
  supply to an area of the brain
• Three main causes
• (1) in thrombosis a plug (a thrombus) becomes
  lodged at its site of formation
• the plug may be due to a blood clot, fat,
  cancerous cells, etc.
• (2) in embolism a plug (an embolus) travels from
  its site of formation and becomes lodged in a
  smaller blood vessel
• (3) in arteriosclerosis the blood vessel walls
  thicken and the space inside narrow
• usually from the accumulation of fat

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Cerebral Ischemia

• The brain damage caused during an ischemic
  episode is believed to be due to an excessive
  release of excitatory amino acids
• Glutamate, the brains most prevalent excitatory
  amino acid neurotransmitter, is released in
  excessive quantities when blood vessels are
  blocked

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Cerebral Ischemia

• The excessive glutamate over-activates glutamate
  receptors on postsynaptic membrane sites
• NMDA (N-methyl-D-aspartate) receptors
• Thus, too many Na and Ca ions are allowed to
  enter the postsynaptic neuron
• The over abundance of Na and Ca triggers
• (a) an excessive release of glutamate, causing a
  cascade of this toxic effect
• (b) triggers a sequence of reactions that kills
  the postsynaptic neuron
• They are excited to death

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Cerebral Ischemia

• The brain damage caused by ischemia takes a while
  to develop (days)
• Does not occur equally in all regions of the
  brain
• Hippocampus is particularly vulnerable
• Researchers are currently studying the ability of
  NMDA receptor blockers administered directly
  after a stroke to reduce subsequent brain damage

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Closed-Head Injuries

• A brain contusion is an injury in which there is
  bleeding from the brain in the absence of a
  laceration
• the bleeding results in a hematoma (a bruise or
  collection of clotted blood)
• contusions are caused by the brain hitting the
  skull, and they are often contre coup (on other
  side of brain from blow)
• Concussion is the diagnosis when a blow to the
  head disrupts consciousness, but no evidence of
  physical damage can be found
• the punch-drunk syndrome is general dementia due
  to an accumulation of many concussions
• The case of Jerry Quarry

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Infections

• Encephalitis is the general term for inflammation
  of the brain resulting from infection
• Bacterial infections can be treated with
  antibiotics, but if left untreated they can cause
  
• meningitis (inflammation of meninges)
• brain abscesses (pockets of pus),
• general paresis (a syndrome of weakness and
  dementia)
• Syphilis passed through contact with genital
  sores
• Can remain dormant for several years, then turn
  virulent and attack many parts of the body,
  including the brain
• General paresis

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Infections

• Viral infections include
• infections that preferentially attack the nervous
  system (e.g., rabies virus)
• infections that show no preference for the
  nervous system but still sometimes attack it
  (e.g., mumps and herpes viruses)
• Viruses may play a key role in the etiology of
  many neuropsychological disorders
• Their role is often hard to study because they
  may lie dormant
• not produce symptoms until years after they
  invade the nervous system

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Neurotoxins

• Brain damage can be produced by a variety of
  toxins in the environment
• "mad hatters" were the result of mercury
  poisoning
• Mercury in the felt
• "crackpots" were originally those who drank tea
  from cracked ceramic pots with lead cores
• Sometimes drugs used to treat a disease can have
  neurotoxic effects
• Tardive dyskinesia is a disorder produced by
  prolonged exposure to certain antipsychotic
  medications

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Questions for Film

• What are symptoms of Parkinsons Disease?
• What happens in the brain that produces
  Parkinsons disease?
• What causes Parkinsons disease?
• What was the initial treatment for Parkinsons
  disease that was discussed in the film.
• L-Dopa what is it?
• What was the problem with this treatment?
• Where did the Mexican surgeons get the cells they
  implanted in the Parkinsons patients?
• Where did the Swedish surgeons get the cells they
  implanted in the Parkinsons patients?
• Where did the Swedish surgeons implant the stem
  cells in the MPTP patients brains? Caudate and
  Putamen
• Why there and not the Substantia Nigra?
• Why did the procedure work better for MPTP
  patients than for traditional Parkinsons
  patients?
• What was one of the big advantages of discovering
  the MPTP molecule?
• Animal models deprenyl monoamine agonist
  MAO inhibitor
• Why was it that the Swedes did not use Connie as
  a subject at first.