BRAIN DAMAGE AND HUMAN NEUROPSYCHOLOGICAL DISEASES

1. 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. Alzheimer’s Disease • Transgenic Mouse Model of Alzheimer’s Disease • c. Parkinson’s Disease • MPTP Model of Parkinson's Disease

2. 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

5. 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.

6. 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

7. 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 brain’s most prevalent excitatory amino acid neurotransmitter, is released in excessive quantities when blood vessels are blocked

8. 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

10. 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

11. 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

12. 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

13. 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

14. 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

19. Questions for Film • 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. • L-Dopa – what is it? • What was the problem with this treatment? • 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 • 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? • Animal models – deprenyl – monoamine agonist = MAO inhibitor • Why was it that the Swede’s did not use Connie as a subject at first.