1 / 60

Brain Damage & Recovery

Brain Damage & Recovery. Causes of brain damage Some examples of brain damage Effects of brain damage Recovery from brain damage Myelination disorders. Causes of Brain Damage. Genetic (not necessarily hereditary!) Congenital Environmental (toxins) Neoplasms

freira
Download Presentation

Brain Damage & Recovery

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Brain Damage & Recovery • Causes of brain damage • Some examples of brain damage • Effects of brain damage • Recovery from brain damage • Myelination disorders

  2. Causes of Brain Damage • Genetic (not necessarily hereditary!) • Congenital • Environmental (toxins) • Neoplasms • Apoptosis (programmed cell death) • Cerebrovascular problems • Head impact injuries (closed head) • Infections

  3. Hereditary Brain Damage • Passed from parent to child through DNA. • Several types: • Faulty chromosome duplication • Rare • Dominant gene disorders • Rare, tend to be self-limiting. • Recessive gene disorders • Not all children express the defect. • Polygenetic disorders • By far the most common.

  4. Faulty Chromosome Duplication • Trisomies • Patau’s Syndrome (trisomy 13) • Cleft lip, polydactyly, heart, stillborn or die young. • Edward’s Syndrome (trisomy 18) • Multiple major abnormalities & MR • Down’s Syndrome (trisomy 21) • MR, Alzheimer’s • Others • Turner’s Syndrome (X0) • Klinefelter’s Syndrome (XXY)

  5. Dominant Gene Disorders • Normally the disorders prevent their own reproduction, with two exceptions: • Disorder limited to rare environmental conditions. • Disorder manifests itself later in life. • Pubertal changes required for gene expression • Adult onset. • Huntington’s disease (Huntingtin, 4p16.3) • Early-onset Parkinson’s (pre-50, chr. 4 & 6) • (not all Parkinson’s cases are genetic)

  6. Recessive Gene Disorders • Single defective gene is passed from parents to children, but only ~25% of children express (or know of) the disorder. • Often affects myelination of cerebral neurons. • Pelizaeus-Merzbacher brain sclerosis • PLP (proteolipid protein), Xq21.3-q22. • Adrenoleukodystrophy (ALD) • Xq28 mutation causes peroxisomes to lose the ability to breakdown very long chain fatty acids (VLCFAs). VLCFAs degrade both myelin and the adrenal gland.

  7. Polygenetic Disorders • Requires the presence of multiple defective genes, along with environmental influences. • Most psychological disorders & personality traits. • Genetics can also protect against disorders.

  8. Congenital Brain Disorders • In-womb damage • Typically due to maternal toxin exposure • Fetal Alcohol/Narcotic Syndrome (FAS/FNS) • Prescription drugs • Thalidomide – “seal limb” • DES (synthetic estrogen) – 50% vaginal cancer by age 10 • Birth Trauma • Hypoxia due to umbilical strangulation • Forceps damage during delivery • Gonorrhea and herpes infections

  9. Environmental • Toxins • Ingested toxins (alcohol, drugs, etc.) • Heavy metal (mercury, lead, etc.) poisoning • Radiation (fallout, exposure, X-rays, etc.) • Radiation can cause genetic mutations. • Drugs • Drugs of abuse • Aspirin – Reye’s Syndrome • Nutritional problems

  10. Neoplasms (Cancers) • Mass of new tissue (= “new growth”). • Physiologically useless. • Growth is usually not controlled. • Neoplasms account for a relatively high proportion of neurological disease. • Brain is 2nd only to uterus as tumor area. • Brain tumors typically not from nerves. • Gliomas account for 45% of brain neoplasms

  11. Neoplasms • Two types of tumors • Benign (-omas) • Regular, well-defined shape. • Does not intrude into surrounding tissue. • Effects only by pressure on the brain. • Malignant (-carcinomas) • Irregularly shaped. • Intrudes (infiltrates) into surrounding tissue. • Tend to be recurrent.

  12. Neoplasms • Astrocytomas • 40%, slow growing, good prognosis • Glioblastomas • 30%, M, >30, highly malignant, < 1 year. • Meduloblastomas • 11%, children only, 1.5-2 years • Meningioma • Most benign of brain tumors, well encapsulated. Glioblastoma

  13. Neoplasms • Metastatic Tumors • Cancerous cells migrate from other parts of the body, normally the lung or breast. • It is not uncommon for lung cancers to first be noticed in the brain. • Normally multiple implant sites. • All malignant. • Very hard to treat.

  14. Cell Death • Apoptosis • Death by suicide • Normal housekeeping • Shrivel and waste • Slow death, days • No inflammation • Nucleus affected from the beginning • More prevalent in early development • Necrosis • Externally caused • Death by injury • Cells swell and rupture • Death is swift, < 1 hour • Surrounding area becomes inflamed • Nucleus not affected until the very end

  15. Cerebrovascular Damage • Brain is well-protected against vascular problems. • Bilateral independent arterial supply both front and back. • Circle of Willis

  16. Cerebrovascular Damage

  17. Cerebrovascular Damage • Aneurysms = weakened/expanded blood vessels • Take up space normally occupied by brain. • Ruptured aneurisms = hemorrhage • Stroke / cerebrovascular accident (CVA). • Arteriosclerosis • Hardening/narrowing of arteries. • Cerebral thrombosis • Lodged embolus causes ischemia and infarction.

  18. Aneurysm • Weakened and/or expanded blood vessels, or pouches. • Can burst causing hemorrhage, infarction & ischemia.

  19. Aneurysm of aortic arch

  20. Arteriosclerosis • Arteries get clogged • Fat & cholesterol • Blocks oxygen delivery. • Partial obstructions require increased blood pressure to push blood past obstruction. • Elevated BP can rupture aneurysms.

  21. Thrombosis • Floating body lodges in vessel. • A 70-year-old woman presented to the emergency room with an acute onset of left arm weakness, difficulty walking and slurred speech. • DX: Acute cerebral infarct from right MCA thrombosis.

  22. Thrombosis

  23. Thrombosis

  24. Cerebrovascular Damage • Formerly assumed that most damage was due to decreased oxygen and/or glucose. • Now appears that most cerebrovascular damage is due to excess glutamate release by blood-deprived neurons. • Excess Ca++ and Na+ influx, especially through NMDA receptors, kills cells. • Hippocampus is particularly affected. • Ca++ channel & NMDA receptor blockers helpful in preventing post-stroke damage.

  25. Head Impact Injuries • Car accidents • Household accidents • Falling down stairs • Bike/scooter/Rollerblade accidents • Shaken baby syndrome • Physical abuse

  26. Head Impact Injuries • Contusions (= bruise) • Damage to the vascular system. • Hematomas - localized collections of blood. • Subdural - beneath (inside) the dura • Epidural - on top of (outside) the dura • Many are contrecoup, opposite to blow.

  27. Head Impact Injuries • Concussion • Disturbance of consciousness without evidence of contusion or other structural damage. • Common assumption is temporary disruption with no long-term damage. • Punch-drunk syndrome suggests otherwise. • Boxers show cerebral scarring with dementia.

  28. Other CNS Injuries • Primarily spinal cord • Slipped disk • Intervertebral disk presses into cord. • Vertebral fracture • Spinal cord can be transected, with varying disabilities.

  29. Infections • Bacterial • Streptococcus • Sore throat, OCD, ADHD • Syphilis (shown) • General pariesis – insanity and dementia • Neisseria meningitidis • Campylobacter jejuni • Common intestinal bacteria • Clostridium tetani (tetanus) • Neurotoxin that blocks cholinesterase

  30. Infections • Viral • Rubella (German measles) • Rubeola (measles) • Varicella/Zoster (chicken pox/shingles) • Mumps • Poliomyelitis • Cytomegalovirus (CMV) • Epstein-Barr virus • Rabies • Herpes

  31. Infections • Encephalitis - inflammation of brain • Bacteria and/or viruses – herpes (shown) measles, chicken pox, mumps, etc. • Sometimes passed by mosquitos or animals. • Can have high mortality rate.

  32. Infections • Meningitis - inflammation of the meninges • Bacteria, viruses, funguses, toxins. • Bacterial form (Neisseria meningitidis) most common. • Viral form most deadly. • Often mistaken for flu: fever, aches, stiffness. • Drowsiness, stupor, seizures, then coma.

  33. Effects of Brain Damage • Kill neurons • Damage to nerve itself • Damage to glial cells/altered environment • Damage to pre-/post-synaptic nerves • Crowd out or put pressure on the brain • Disable neurons • Often by interfering with myelin

  34. Recovery of Function

  35. Recovery of Function • What happens after (or during) brain damage? • Degeneration • Regeneration • Reorganization • Can anything be done to aid recovery?

  36. Degeneration • Damaged neurons degenerate over days by the process of phagocytosis: • By astroglia in CNS. • By Schwann cells in the PNS.

  37. Degeneration • Anterograde – segments distal to soma: • Always die thru Wallerian degeneration. • Swell within hours, fragment within days • Distal neurons can also be affected. • Retrograde – segments proximal to soma: • Might die, might live. • Early swelling = regeneration likely • Early shrinking = degeneration likely • Proximal neurons can also be affected.

  38. Regeneration • Damaged neurons may regrow. • Regeneration is well developed in invertebrates. • Accurate in both the CNS and PNS. • Accurate even when not in a myelin channel. • Mammals seem to lose their regeneration capabilities during maturation. • Almost non-existent in mammalian CNS. • Hit-or-miss in mammalian PNS.

  39. Regeneration • Regeneration in mammals depends on the balance of two competing factors: • Growth promoting factors (higher in PNS) • Neural growth factor (NGF) • Brain-derived neurotrophic factor (BDNF) • Growth inhibiting factors (higher in CNS) • Nogo • Myelin-associated glycoprotein (MAG) • Chondroitin sulfate proteoglycan (CSPG) • Oligodendrocyte myelin glycoprotein (OMG)

  40. Regeneration in PNS • If myelin sheaths remain intact, nerve can regrow at mm/day to original destination. • If nerve sections are separated by more than a couple mm, they can grow back thru the wrong myelin tunnels. • If nerves sections are widely separated, both sections will die, or regenerating axon tips will grow wildly into a spaghetti patch.

  41. Regeneration • Collateral sprouting • When axons degenerate, adjacent healthy neurons send out axon branches from terminal end or nodes of Ranvier to sites vacated by the dying neuron. • Appears to be mediated by neurotrophic factors released by the denervated target tissue.

  42. Neural Reorganization • aka. Plasticity • The ability of the brain to remap its functioning. • 2 Mechanisms: • Rapid reorganization • Altered synaptic strengths • Gradual reorganization: • Establishment of new connections • Collateral sprouting, etc. • Damage repair

  43. Neural Reorganization • The extent and mechanisms of neural reorganization are still being debated. • 3 general conclusions • Bona fide recovery is rare. • Small lesions are more likely to be recovered. • Recovery is more likely when young.

  44. Therapeutic Implications • Promotion of recovery by neurotransplantation • PNS neurons secrete NGFs and will cause nearby CNS neurons to grow. • Cheng, Cao & Olson (1996) cut an optic nerve, spliced in a PNS nerve segment, and found retinal axon cells projecting to superior colliculus 4 months later. • NGF injection into human CNS promotes a little growth. Anti-nogo allows ~5% regrowth.

  45. Therapeutic Implications • Promotion of recovery by rehabilitative training. • At least in motor cortex, greater use = less loss of function (or greater recovery). • Recovery of monkeys with hand motor cortex lesions improved with hand motor tasks. • Humans with spinal cord injuries learn to walk better with rehabilitative treatment than with just physiotherapy.

  46. Therapeutic Implications • Promotion of recovery by genetic engineering. • The promise of the future. • Since CNS nerves do not grow because of lack of neural growth factor (NGF), the idea is to introduce some from stem cells or altered viruses. • Nogo also prevents the growth of nerves. Maybe it can be artificially inhibited. Experimental nogo antagonists have been found.

  47. Myelination Disorders

  48. Myelination Disorders • Dysmyelination – poor myelin formation • Early in life, mostly genetic. • Many disorders • Many affect connection between myelin layers. • Demyelination – myelin destroyed • Later in life, some genetic, mostly autoimmune.

  49. Myelination Diseases • Dysmyelination • leukodystrophies (ALD, PMD, Krabbe) - CNS • Demyelination • Guillan-Barré Syndrome (GBS) - PNS • Acute Disseminated Encephalomyelitis (ADEM) CNS • Multiple Sclerosis (MS) - CNS • Combination • Charcot-Marie-Tooth Disease (CMT) – PNS

More Related