CH 10: Brain Damage & Neuroplasticity Flashcards
Define TUMOUR.
- A mass of cells growing independently of rest of body
Explain difference b/w ENCAPSULATED vs. INFILTRATING brain tumour.
- Encapsulated Tumours = grows w/in their own membrane
- -> usually are BENIGN Tumours = can be surgically removed w/ little risk of further growth in body
- Infiltrating Tumours = grows diffusely through surrounding tissues
- -> usually are MALIGNANT Tumours = difficult to remove/destroy completely
- -> any cancerous tissue that remains after surgery cont. to grow
- ie) Gliomas = brain tumours that develop from glial cells
List the 2 types of brain tumours.
- Meningiomas
2. Metastatic Tumours
Describe MENINGIOMAs.
- Tumours that grow b/w the meninges (=the 3 membranes that cover the CNS)
- All meningiomas = Encapsulated tumours
- -> Usually benign tumours
Describe METASTATIC Tumours.
- Don’t originate in brain but grow from infiltrating cells that are carried to brain via bloodstream from some other body part
Define a STROKE.
- Sudden-onset cerebrovascular disorders that cause brain damage
List the 2 types of stroke.
- Cerebral Hemorrhage
2. Cerebral Ischemia
Describe a CEREBRAL HEMORRHAGE.
Cerebral Hemorrhage:
= Bleeding in brain
- Occurs when a cerebral bv ruptures & blood seeps into surrounding neural tissue & damages it
- Commonly caused by burst aneurysm
- ANEURYSM = ballon-like dilation formed in artery wallet point where elasticity of artery wall is defective
Describe CEREBRAL ISCHEMIA.
Cerebral Ischemia:
= disruption of the blood supply to an area of the brain.
Describe the 3 main causes of Cerebral Ischemia.
- THROMBOSIS
= a plug called a thrombus is formed & blocks blood flow at with of its formation - EMBOLISM
= similar to 1., except that the plug, called an emboli, is carried by the blood from a larger vessel, where it was formed, to a smaller one, where it becomes lodged
- aka a thrombosis that’s taken a trip - ARTERIOSCLEROSIS
= walls of blood vessels thicken & channels narrow
–> usually as result of fat deposits
–> narrowing leads to complete blockage of the bv
List the 2 important properties of ischemia-induced brain damage.
- Takes a while to develop
- It doesn’t occur equally in a all parts of brain
- -> Particularly susceptible neurons are in certain areas of hippocampus
Describe how GLUTAMATE plays a major role in ischemia-induced brain damage.
- GLUTAMATE = brain’s most prevalent excitatory NT
- After a bv becomes blocked, many blood-deprived neurons become overactive & release ^^glutamate
- -> Glutamate over activates glutamate receptors in membranes of postsynaptic neurons
- -> ^Na & Ca2+ ions enter postsynaptic neurons
Excessive internal Na & Ca [ ]s affects postsynaptic neurons by… (2)
- Triggering release of excessive amounts of glutamate from the neurons
- -> Spreads toxic cascade to other neurons - Triggers sequence of internal reactions that ultimately kill the postsynaptic neurons
Define CLOSED-HEAD INJURIES.
- Brain injuries produced by blows that do NOT penetrate skull
Describe a CONTUSION.
Contusion:
- Closed-head injury involving damage to cerebral circulatory system
- Produced internal hemorrhaging
- -> results in HEMATOMA = localized collection of clotted blood in organ/tissue = bruise
- Occurs when brain slams against inside of skull
- Frequently occurs on side of brain opposite to side struck by blow (bc brain strikes inside of skull on other side of head)
Describe a CONCUSSION.
Concussion:
- Disturbance of consciousness following blow to head & no evidence of a contusion or other structural damage
- Its effects can last years
- Effects of repeated concussions can accumulate
- ie) memory loss in football players
Define a BRAIN INFECTION.
- An invasion of the brain by microorganisms
List the 2 different types of infections of the brain.
- Bacterial infections
2. Viral infections
Describe BACTERIAL INFECTIONS of the brain.
- Bacteria infect brain
- -> Lead to formation of CEREBRAL ABSCESSES = pus pockets in brain
- Bacteria = major cause of meningitis = inflammation of meninges
Describe the 2 types of VIRAL INFECTIONS of the brain.
- 2 types of viral infections of NS:
(a) those w/ particular infinity for neural tissue
(b) those that attack neural tissue but have no greater affinity for it than other tissues - ie) rabies = virus w/ particular affinity for NS
Describe 3 different types of NEUROTOXINS.
- HEAVY METALS
- ie) mercury & lead
- Can accumulate in brain & permanently damage it
- -> Produce toxic psychosis = mental illness produced by neurotoxin
- ie) Madhatter = hat makers inhale mercury when making hats - DRUGS USED TO TREAT NEUROLOGICAL DISORDERS
- Proven to be toxic - Some neurotoxins = ENDOGENOUS = produced by patient’s own body
- ie) produce antibodies that attack particular components of NS
- ie) glutamate & ischemic stroke – excessive release of NT can damage brain
Discuss symptoms of DOWN SYNDROME & what causes this disorder.
Down Syndrome:
- Disorder ass w/ presence of extra chromosome 21
- Results in characteristic disfigurement & intellectual impairment
- Genetic accident
- -> Extra chromosome 21 created in egg during ovulation
Describe APOPTOSIS.
Apoptosis:
= Programmed cell death
- Critical in early development (eliminates extra neurons)
- Causes brain/neural damage
–> Is activated by tumours, cerebrovascular disorder, closed-head injuries, infections, toxins , & genetic factors
- Slow death (1-2d)
- Gradual, starting w/ shrinkage of cell body
–> parts of neuron die
–> debris packaged in vesicles
–> no inflammation = minimal damage to nearby cells
Describe NECROSIS.
Necrosis:
= Passive cell death resulting from INJURY
- Quick death (1-2h)
- Damaged neuron swells & breaks apart, beginning in axons & dendrites &; ending in cell body
–> Fragmentation leads to inflammation
–> Damage other nearby cells
Describe EPILEPSY.
Epilepsy:
= Neurological disorder characterized by spontaneously recurring seizures
- Hard to diagnose bc some epileptic seizures don’t affect motor function
–> Rather subtle changes in mood, thought or behaviour
What are some causes of epilepsy (4)?
- Viruses
- Neurotoxins
- Tumours
- Blows to head
Describe the difference b/w/ FOCAL Seizures & GENERALIZED Seizures.
- FOCAL Seizure = doesn’t involve entire brain
- GENERALIZED Seizure = involves entire brain
Describe Focal Seizures & list the 2 categories of Focal Seizures.
Focal Seizure:
- Epileptic neurons at a focus discharge together in bursts
- -> Synchronous bursting neurons produce epileptic spiking in EEG
- -> Spreads to other areas of brain, but not entire brain
- -> Usually accompanied by total loss of consciousness
Categories:
- Simple Partial Seizures
- Complex Partial Seizures
Describe Simple Partial Seizures.
Simple Partial Seizures:
= Focal seizures whose symptoms are primarily sensory or motor or both
- As epileptic discharges spread through sensory or motor areas of brain, the symptoms spread systematically through body
Describe Complex Partial Seizures.
Complex Partial Seizures:
= Restricted to temporal lobe
- Patient engages in compulsive, repetitive, simple behaviours (ie. doing & undoing a button)
- Engages in ^complex behaviours that appear almost normal
Describe Generalized Seizures & list the 2 categories of Generalized Seizures.
- Discharges begin simultaneously in all parts of brain
- OR begin as focal discharges that gradually spread through entire brain
Categories:
- Tonic-Clonic Seizures
- Absence Seizure
Describe Tonic-Clonic Seizures - what are its primary behavioural symptoms?
Primary behavioural symptoms:
- Loss of consciousness
- Loss of equilibrium
- Tonic-Clonic Convulsion = TONIC (rigid body) then CLONIC (uncontrollable jerking)
Describe Absence Seizures - what are its primary behavioural symptoms?
Primary behavioural symptoms:
- Disruption of consciousness ass. w/ cessation of ongoing behaviour, vacant look & fluttering eyelids
Describe the treatments for epilepsy (4).
- No cure for epilepsy, but the frequency & severity of seizures can be reduced by anti-epileptic meds
- -> Though these drugs have adverse side effects & don’t work for everyone
Other treatments include:
- Stimulation of vagus nerve
- Transcranial magnetic stimulation
- Ketogenic diet = high fat, moderate protein, low carbs
Describe PARKINSON’s DISEASE (PD).
- Movement disorder of middle & old age
- -> affects 1% of pop >55yo
Describe the symptoms of PD.
- Mild initial symptoms = slight stiffness or finger tremor
Symptoms ^severity w/ advancing years ie)
- Pronounced tremor during inactivity
- Muscular rigidity
- Difficulty initiating movement
- Slowness of movement
- Mask-like face
- Pain & depression
Describe some treatments for PD (2).
- L-dopa Injections
- -> but NOT a permanent solution
- -> becomes less effective w/ continued use, until its side effects (ie. involuntary movements) outweigh its benefits - Deep Brain Stimulation
= low-intensity electrical stimulation continuously applied to area of brain via implanted electrode
- ^controversial
Describe the symptoms of HUNTINGTON’s DISEASE.
Huntington’s Disease:
= Progressive motor disorder
- 1st sign - ^fidgetiness
- Develop rapid, complex, jerky movements of entire limbs (rather than individual muscles)
- Eventually motor & intellectual deterioration so severe that sufferers are incapable of feeding themselves, control bowels, or recognize own kids
- NO CURE – death ~15y after presence of 1st symptoms
What makes Huntington’s Disease different from PD (3)?
- Unlike PD, it’s:
> Rare (1:10k)
> Has simple genetic basis
> Is always ass. w/ severe dementia
Explain the genetic basis of Huntington’s Disease.
- Passed from generation to generation via single mutated dominant gene (huntintin)
- Dominant = all individuals w/ the gene will have the disorder & pass onto 1/2 offspring
Describe MULTIPLE SCLEROSIS (MS) - what happens to the NS?
Multiple Sclerosis (MS):
= Progressive disease that attacks the myelin of axons in the CNS
- Attacks in early adulthood
- 1st see microscopic areas of degeneration on myelin sheath
–> Damage to myelin so severe that associated axons become dysfunctional & degenerate
–> Ultimately form many areas of hard scar tissue in CNS (sclerosis = hardening)
= Autoimmune disorder = body’s immune sys attacks part of body as if it were foreign substance
Describe the symptoms of advanced MS (6).
- Visual disturbances
- Muscular weakness
- Numbness
- Tremor
- Ataxia = loss of motor coordination
- Cognitive deficits & emotional changes in some ppl
Describe the symptoms of ALZHEIMER’s DISEASE (AD) - early, intermediate, & advanced stages.
Alzheimer’s Disease:
- Most common cause of dementia in the elderly
- NO CURE –> Terminal
- Major genetic component
- Progressive, early stages = memory loss, attention deficits, personality changes
- Intermediate stages = concussion, irritability, anxiety, deteriorated speech
- Advanced stages = ^deterioration
- -> can’t control simple responses ie) swallowing & bladder control
What are the 3 defining characteristics of AD?
- Neurofibrillary Tangles
= Tangles of protein in neural cytoplasm - Amyloid Plaques
= Clumps of scar tissue composed of degenerating neurons - Neuron loss
- -> All 3 ^prevalent in medial temporal lobe structures
- ie) entorhinal cortex, amygdala & hippocampus
- -> all involved in various aspects of memory
- All 3 also more prevalent in temporal cortex, posterior parietal cortex, & prefrontal cortex
- -> all mediate complex cognitive function
Evaluate the AMYLOID HYPOTHESIS (the evidence for and against it).
Amyloid Hypothesis:
= Amyloid plaques are the primary symptom of AD & cause all other symptoms
> SUPPORT:
- via genetic analysis
- all 3 diff gene mutations that cause early-onset AD influence the synthesis of beta-amyloid
> AGAINST:
- via fact that many ppl w/o observable dementia carry ^^amyloid plaques = high-plaque normals
- However, high-plaque normals have ^^risk of cognitive decline & some develop AD
Describe the KINDLING model of epilepsy.
Kindling Phenomenon:
= Progressive development & intensification of convulsion elicited by a series of periodic low-intensity brain stimulation
- Most frequently studied in rats subjected to repeated AMYGDALA stimulation (electrical)
- Neuroplastic changes underlying kindling are permanent
- -> A subject kindled & then left unstimulated for months still responds to each low intensity stimulation w/ a generalized convulsion
- Kindling is produced by distributed (as opposed to massed) stimulation
Explain the 2 ways in which the Kindling model of epilepsy models human epilepsy.
- The convulsions elicited in kindled animals are similar WRT those observed in some types of human epilepsy
- Kindling phenomenon itself is comparable to the epileptogenesis (=development of epilepsy) that can follow a head injury
Describe the way in which the Kindling model of epilepsy does NOT model human epilepsy.
- Kindled convulsions are elicited
- -> Unlike spontaneous seizures in epilepsy
Describe the TRANSGENIC MOUSE models of AD.
- Transgenic = animals w/ inserted genes of another sp
- In transgenic mouse models of AD, gene mutations that promotes he accumulation of human beta-amyloid are injected into newly fertilized ouse eggs
- -> Eggs injected into foster mom to develop
- -> Mutated mice brains contain ^amyloid plaques like those of human Ad
- -> Display neural loss & memory disturbances
Evaluate the 1 problem of transgenic mouse models of AD, & explain its resolution.
- Don’t display neurofibrillary tangles, which are primary symptom of AD
- -> Resolved by injected human gene mutations that promo accumulation of protein tau
Describe the MPTP model of PD, & evaluate the utility of this animal model.
- MPTP = a neurotoxin that produced a disorder in primates that’s similar to PD
- Non-human primates respond to MPTP the same way humans do
- -> Display Parkinson motor symptoms, cell loss in the substance nivea, & reduction in brain dopamine
- Rats are resistant to MPTP
- Although the MPTP model doesn’t model all aspects of PD, particularly its causation, the model’s proven ^^useful
- -> Instrumental in development of many treatments & dopaminergic drugs currently in use
Define NEURAL DEGENERATION - what is it induced by?
- Neural deterioration & death
- Component of both brain development & disease
- Induced by cutting axons
List the 2 kinds of Neural Degeneration.
- Anterograde Degenration
2. Retrograde Degeneration
Describe ANTEROGRADE DEGENERATION.
Anterograde Degeneration:
= Degeneration of the DISTAL segment of a cut axon (=segment of a cut axon from the cut to the synaptic terminals)
- Occurs quickly following axotomy bc cut separates distal segment of axon from cell body (which is metabolic centre of neuron)
–> Entire distal segment becomes ^ swollen w/in hours
–> Breaks into fragments w/in days
Describe RETROGRADE DEGENERATION.
Retrograde Degeneration:
= Degeneration of the PROXIMAL segment of a cut axon (=segment of a cut axon from the cut back to the cell body)
- Gradually progresses back from cut to cell body
- Major changes in cell bodies of most axotomized neurones after 2-3d
Describe TRANSNEURONAL DEGENEATION.
Transneuronal Degeneration:
= Degeneration of a neuron caused by damage to another neuron to which it’s linked by a synapse
Describe ANTEROGRADE vs. RETROGRADE Transneuronal Degeneration.
ANTEROGRADE = transneuronal degeneration spreads from damaged neurons to the neurons on which they synapse
RETROGRADE =
transneuronal degeneration spreads from damaged neurons to the neurons that synapse on them
Define NEURAL REGENERATION.
Neural Regneration:
= Regrowth of damaged neurons
Compare Neural Regeneration w/in the CNS vs. the PNS.
- Doesn’t process as successfully in mammals & other higher vertebrates as it does in invertebrates & lower vertebrates
- Is non-existent in CNS of adult mammals, & at best a hit-or-mess in PNS
- In mammalian PNS: regrowth from proximal stump of damaged nerve begins 2-3d after axonal damage, once new growth cones have formed
see pg 259-261
Describe the 1st example of cortical reorganization following damage to the brain, & discuss the mechanisms that might underlie such recognition.
- Cortical Reorganization following damage in LAB ANIMALS:
- Sensory & motor cortex ideally suited to study neural reorganization bc of their topographic layout
- Damage-induced reorganization of primary sensory & motor cortices have been studied under 2 conditions:
(a) following damage to peripheral nerves
(b) following damage to cortical areas themselves
see pg 262 for 3 influential studies demo cortical reorganization
Describe the 2nd example of cortical reorganization following damage to the brain, & discuss the mechanisms that might underlie such recognition.
- Cortical Reorganization following damage in HUMANS:
- Use brain imaging techniques to study cortices of blind ppl
- -> Findings consistent w/ hypo that there’s continuous competition for cortical space by functional circuits
- W/o visual input to cortex, there’s expansion of auditory & somatosensory cortex, & auditory & somatosensory input is processed in formerly visual areas
- Functional consequence to this reorganization = blind volunteers have skills superior to those of slighted control on a variety of auditory & somatosensory tasks
Describe 2 mechanisms of Neural Reorganization.
- Strengthening of existing connections, possibly via release from inhibition
- Indirect support comes from 2 observations:
(a) reorganization occurs too quickly to be explained by neural growth
(b) rapid reorganization never involves changes of >2mm of cortical surface - Establishment of new connections by collateral sprouting
- Indirect support comes from 1 observation:
(a) the magnitude of long-term reorganization can be too great to be explained by changes in existing connections
see Figure 10.8 to see how 2 mechanisms may account for reorganization that occurs after damage to peripheral somatosensory nerve
.. do it?
Describe the concept of COGNITIVE REVERSE.
Cognitive Reverse:
- Thought to play a role in the improvements observed after brain damage that do NOT result from true recovery of brain function
- ie) brain damage patients who demo improvement bc cognitive reverse allowed them to accomplish tasks in alternative ways
- Explains why educated ppl are less susceptible to the effects of brain deterioration ass. w/ aging
Does adult neurogenesis contribute to recovery from brain damage?
- NO direct evidence that stem cells contribute to recovery!
- Although stem cells can migrate short distances, there’s no evidence they can migrate from their sites of genesis in hippocampus to distant areas of damage in adult human brain
Discuss early work on neuro-transplantation for the treatment of CNS damage.
- Explore possibility of repairing damaged CNS tissue via implanting embryonic tissue near damaged area
- -> Hope embryonic tissue would mature & replace damaged cells
- Focused on using as treatment for PD
- Initial success & reduced symptoms, but patients displayed uncontrollable writing & chewing movements 1yr after surgery
Discuss the methods & findings of modern research on neuro-transplantation.
- ^^animal models of all common neurological disorders
- Suggest stem-cell cultures provide lasting sources of cell transplantation
- -> Ethical & technical difficulties in transplanting tissue obtained from human embryos
- -> DIDN’T work out – stem-cell cultures deteriorate as chromosomal abnormalities gradually accumulate during repeated cell division
Discuss methods of treating STROKES through rehabilitate treatment.
- Small strokes produce core of brain damage
- -> Followed by a gradually expanding loss of neural function in the surrounding penumbra
- Study prod small ISCHEMIC LESIONS in hand area of motor cortex of monkeys
- -> Initiate program of hand training & practice
- -> Reduced expansion of cortical damage into surrounding penumbra
Discuss methods of treating SPINAL INJURY through rehabilitate treatment.
- Patients incapable of walking were supported by harness over a moving treadmill
- -> Weight was supported & treadmill provided feedback
- -> Gradually learn to make walking movements
Describe the benefits of cognitive & physical exercise.
- Study benefits of cognitive & physical activity by assessing the neurological benefits of housing animals in ENRICHED environments
- -> Enriched environ show to ^dendritic branching, the site of synapses, the rate of adult neurogenesis, & the levels of various neurotrophic factors
- Physical exercise in form of daily wheel running
- -> Beneficial effects on rodent brain
- ie) ^adult neurogenesis in hippocampus
- reduced age-related declines in # neurons in hippocampus
- improved performance on memory & navigation tests (2 abilities linked to hippocampus)
Discuss ways of treating phantom limbs.
- Surgical efforts to control irritation at stump via cutting off stump or various ways of neural pathway b/w stump & cortex
- -> unsuccessful :(
