BRAIN DAMAGE AND
HUMAN NEUROPSYCHOLOGICAL
DISEASES
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Outline
1. Causes of Brain Damage
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a. Tumors
b. Cerebrovascular Disorders
c. Closed-Head Injuries
d. Infections
e. Neurotoxins
2. Neuropsychological Diseases
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a. Epilepsy
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b. Alzheimer’s Disease
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Kindling Model of Epilepsy
Transgenic Mouse Model of Alzheimer’s Disease
c. Parkinson’s Disease
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MPTP Model of Parkinson's Disease
Causes of Brain Damage:
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Tumors
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A tumor (neoplasm) is a group of cells growing independently of
the rest of the body
a tumor can be
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Encapsulated (grow within their own membrane)
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Infiltrating (grow diffusely through surrounding tissue)
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Usually malignant (difficult to remove or destroy and likely to
spread)
Metastatic tumors are tumors that originate in one organ and spread
to another
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usually benign (can be removed without further risk of growth)
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
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they are encapsulated and benign
Cerebrovascular Disorders
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“Stroke" is commonly used to refer to any
cerebrovascular disorder of sudden onset
Two types
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1) cerebral hemorrhage
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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.
Cerebrovascular Disorders
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2) Cerebral ischemia is a disruption of blood
supply to an area of the brain
Three main causes
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(1) in thrombosis a plug (a thrombus) becomes lodged at
its site of formation
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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
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usually from the accumulation of fat
Cerebral Ischemia
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The brain damage caused during an
ischemic episode is believed to be due
to an excessive release of excitatory
amino acids
Glutamate, the brain’s most prevalent
excitatory amino acid neurotransmitter,
is released in excessive quantities when
blood vessels are blocked
Cerebral Ischemia
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The excessive glutamate over-activates glutamate
receptors on postsynaptic membrane sites
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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
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(a) an excessive release of glutamate, causing a cascade of
this toxic effect
(b) triggers a sequence of reactions that kills the
postsynaptic neuron
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They are excited to death
Cerebral Ischemia
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The brain damage caused by ischemia takes
a while to develop (days)
Does not occur equally in all regions of the
brain
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Hippocampus is particularly vulnerable
Researchers are currently studying the ability
of NMDA receptor blockers administered
directly after a stroke to reduce subsequent
brain damage
Closed-Head Injuries
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A brain contusion is an injury in which there is
bleeding from the brain in the absence of a
laceration
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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
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the punch-drunk syndrome is general dementia due to an
accumulation of many concussions
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The case of Jerry Quarry
Infections
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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
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meningitis (inflammation of meninges)
brain abscesses (pockets of pus),
general paresis (a syndrome of weakness and dementia)
Syphilis – passed through contact with genital sores
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Can remain dormant for several years, then turn virulent and
attack many parts of the body, including the brain
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General paresis
Infections
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Viral infections include
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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
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Their role is often hard to study because they may
lie dormant
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not produce symptoms until years after they invade the
nervous system
Neurotoxins
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Brain damage can be produced by a variety
of toxins in the environment
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"mad hatters" were the result of mercury
poisoning
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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
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Tardive dyskinesia is a disorder produced by
prolonged exposure to certain antipsychotic
medications
Questions for Film
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What are symptoms of Parkinson’s Disease?
What happens in the brain that produces Parkinson’s disease?
What causes Parkinson’s disease?
What was the initial treatment for Parkinson’s disease that was discussed in the film.
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Where did the Mexican surgeons get the cells they implanted in the Parkinson’s patients?
Where did the Swedish surgeons get the cells they implanted in the Parkinson’s patients?
Where did the Swedish surgeons implant the stem cells in the MPTP patient’s brains? –
Caudate and Putamen
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Why there and not the Substantia Nigra?
Why did the procedure work better for MPTP patients than for traditional Parkinson’s
patients?
What was one of the big advantages of discovering the MPTP molecule?
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L-Dopa – what is it?
What was the problem with this treatment?
Animal models – deprenyl – monoamine agonist = MAO inhibitor
Why was it that the Swede’s did not use Connie as a subject at first.