10. Brain damage and neuroplasticity Flashcards
(90 cards)
1
Q
What are the causes of brain damage?
A
- brain tumours
- cerebrovascular disorders – cell death
- Closed-head injuries
- infections of the brain
- neurotoxins
- genetic factors
2
Q
Tumour
A
AKA neoplasm
Independently growing cell mass without any physiological function (cancer)
3
Q
What are the types of tumours?
A
- meningiomas
- Infiltrating tumors
- Metastic tumours
4
Q
Meningiomas
A
20% of tumours; grow between meninges; encapsulated (within own membrane), usually benign
5
Q
Infiltrating tumours
A
Most tumours are infiltrating. Grow diffusely through surrounding tissue, typically malignant, difficult to remove or destroy
6
Q
Metastatic tumours
A
10% of brain tumours; originate elsewhere, usually lungs, skin, breasts
7
Q
Define metastasis (NOT metastatic tumours)
A
Transmission of disease form one organ to another
8
Q
Stroke
A
Sudden-onset cerebrovascular accident (CVA) resulting in brain damage
9
Q
What are the types of strokes
A
Cerebro haemorrhage
Cerebral ischemia
10
Q
Cerebral haemorrhage
A
A kind of stroke that involves bleeding in the brain. Caused by burst aneurysms (defective elasticity in artery wall).
11
Q
How do you prevent cerebral haemorrhages?
A
By avoiding rise in blood pressure and strenuous activity
12
Q
Cerebral ischemia
A
A kind of stroke that involves blood supply disruption caused by:
- Thrombosis
- Embolism
- Arteriosclerosis
- Sudden drop in blood pressure
13
Q
Thrombosis
A
A former thrombus blocks artery
14
Q
Embolism
A
Traveling thrombus lodges in narrower artery
15
Q
Arteriosclerosis
A
Thickening of blood vessel walls
16
Q
What are the properties of ischemia?
A
Induced in the brain
Does not develop immediately (a couple of days)
Affect some neurons more than others (e.g. hippocampus)
Different mechanisms for different brain structures
Involves brain’s own neurotransmitter
17
Q
What does ischemia result from?
A
Results largely from excessive excitatory neurotransmitter release – especially glutamate (Excitotoxicity)
As a consequence of blockage, blood-deprived neurons become overactive and release too much glutamate
Glutamate over-activates postsynaptic glutamate receptors, esp. NMDA
Result: influx of Na+ and CA2+ into postsynaptic neurons (concentration abnormally high)
- triggers release of glutamate from postsynaptic neurons (domino effect
- Triggers internal reactions that lead to cell death (apoptosis)
18
Q
What is the process of stroke-induced release of glutamate?
A
- Blood vessel becomes blocked
- Neurons that are affected by the ischemia release of excessive glutamate
- excessive glutamate binds to NMDA receptors, thus triggering an excessive influx of NA+ and CA2+ ions into postsynaptic neurons
- The excessive influx of Na+ and Ca2+ ions eventually kills postsynaptic neurons, but first it triggers the excessive release of glutamate from them thus spreading the toxic cascade
19
Q
What is the sequences of damaging events with stroke?
A
- A blood clot stops the flow of blood to a brain region
- Without oxygen and glucose, neurons begin to depolarise, perhaps because of loss of the sodium-potassium pump. The neurons reach threshold and produce a barrage of action potentials
- Many of these rapidly firing neurons release the excitatory neurotransmitters glutamate. In addition, the lack of energy in the presynaptic neuron causes the glutamate transporters, which normally remove the transmitter from the cleft, to stop working (no reuptake)
- Postsynaptic neurons, bombarded with glutamate, also produce a barrage of action potentials (which may spread the glutamate flood) so excessive amounts of calcium and zinc enter the cell
- The excessive intracellular calcium and zinc trigger cell death (apoptosis), and the neuron has succumbed to excitotoxicity.
20
Q
What are the possible treatments for strokes?
A
Thrombolytics and drugs
21
Q
Thrombolutics as a treatment for strokes
A
Thrombolytics are drugs that dissolve blood clots. Includes tissue plasminogen activator, may restore blood flow to avoid further amage
22
Q
What are the types of drugs that treat stroke?
A
- drugs that inhibit the voltage-gated sodium channel may reduce the number of action potentials generated
- Drugs that block glutamate receptors may combat the excessive stimulation
- Drugs that block calcium channels may avert the intracellular buildup of calcium
23
Q
What are the kinds of cell death?
A
Apoptosis and necrosis
24
Q
Apoptosis
A
Active but gradual self-destructive process
Important adaptive process in limiting brain damage
Important in development: culling excess neurons
25
How does Apoptosis limit brain damage?
Cell body shrinks and remainder of neuron dies, any debris is cleared (vesicles) and thus there is no trauma to surrounding cells
26
Necrosis
Passive and fast but more generally destructive process
Neuron swells and breaks up (axons and dendrites, followed by cell body)
Fragmentation may cause inflammation and damage cells in surrounding tissues
27
Close-head injuries
Brain injuries due to blow that do not penetrate the skull – the brain collides with the skull
28
What are types of close head injuries?
Contrecoup injuries
| Concussion
29
Contrecoup injuries
Contusions are often on side of brain opposite to the blow. e.g. the blow was made at the front but the impact actually occurred at the back.
30
Contusions
Damage to cerebral circulatory system, resulting in internal bleeding and a haematoma
31
Haematoma
Bruise/clotted blood
32
Concussion
Disturbance of consciousness but no evidence of structural damage (e.g. contusion).
Nothing to worry about??? – Punch-drunk syndrome
33
Punch-drunk syndrome
Dementia pugilistic and cerebral scarring
34
What are brain infections caused by?
Invasion by microorganisms → encephalitis – the resulting inflammation
35
What are the types of brain infections?
1. bacterial infections
| 2. viral infections
36
Bacterial infections
Often leads to cerebral abscesses (pockets of pus)
May inflame meninges → meningitis
Syphilis
37
Syphilis
Transmitted via genital sores and can result in general paresis (syndrome consisting of insanity and demetia)
38
Viral infections
Some viral infections preferentially attack neural tissue (e.g. rabies) – virus typically dormant for one month
39
Neurotoxins
```
May enter general circulation from gastrointestila tract, lungs, or through the skin.
These can be endogenous (think glutamate)
Recreational drugs (e.g. alcogol, ecstacy) may cause brain damage – neurotoxic effects of alcohol and thiamine deficiency
```
40
Toxic psychosis
Chronic insanity produced by neurotoxins (e.g. mercury, lead)
Some antipsychotic drugs have toxic effects and produce a motor disorder – tardive dyskinesia
41
How do genetics play a factor in neuropsychological disease?
Most neuropsychological disease of genetic origin are associated with recessive genes
42
What is an example of genetic factors affecting neuropsychological diseases?
Down syndrome
- genetic accident – not faulty gene
- 0.15% of births, probability increases with advancing maternal age
- Extra chromosome 21
- Characteristic disfigurement, mental retardation, other health problems
43
What are some neuropsychological diseases?
Epilepsy
Parkinson’s disease
Alzheimer’s disease
44
Epilepsy
Primary symptom is seizures
Difficult to diagnose – epileptic seizures are diverse and complex
No single cause
45
How are seizures generated?
By chronic brain dysfunction
46
What are the results of epilepsy?
Convulsions – motor seizures
| Subtle changes of thought, mood or behaviour
47
What are the potential causes of epilepsy?
```
Brain damage (many and varied)
Genes → 70 known so far
```
48
How is epilepsy diagnosed?
EEG – Electroencephalogram
| Seizures associated with high amplitude spikes
49
What are the two major groups of seizures?
Partial seizures and generalised seizures
50
What are the two kinds of partial seizures?
Simple partial and complex partial
51
Simple partial seizures
Symptoms are primarily sensory or motor or both (Jacksonian seizures)
Symptoms spread as epileptic discharge spreads
No loss of awareness
52
Complex partial seizures
Often restricted to the temporal lobes (temporal love epilepsy)
- patient engages in compulsive and repetitive simple behaviours – automatisms
- more complex, seemingly normal behaviours also occur
53
What are the two kinds of generalised seizures?
Grand mal and Petit mal
54
Grand mal
Loss of consciousness and equilibrium
Tonic-clonic convulsions – rigidity (tonus) and tremors (conus)
Resulting hypoxia may cause brain damage
55
Petit mal
Not associated with convulsions
Disruptions of consciousness associated with a cessation of ongoing behaviour (petit mal absence)
Different EEG pattern (bilaterally symmetrical 3-per-second spike-and-wave discharge)
56
What is the kindling model of epilepsy?
A series of periodic brain simulations eventually elicits convulsions – kindling phenomenon (Goddard et al., 1969)
- Neueoplastic changes are permanent
- produced by stimulation disturbed over time
57
Why is the kindling model of epilepsy a model of interest?
Because it is elicited it is not spontaneous
1. Convulsions are similar to those seek in some forms of human epilepsy – but they only occur spontaneously if kindled for a very long time
2. Kindling phemenon is comparable to the development of epilepsy (epileptogenesis) seen following a head injury
58
Parkinson’s disease
Progressive motor disorder
Pain and depression common before full disorder develops
Cognitive deficits emerge by dementia is not typically seen?
59
What the common symptoms of Parkinson’s Disease?
Tremor at rest
60
What are the causes of Parkinson’s disease?
No single clause
Associated with degeneration of the substantia nigra (dopaminergic neurons)
Almost no dopamine in the substantia nigra and straitum of Parkinson’s patients
61
How is Parkinson’s Disease treated?
Temporarily with L-dopa
62
What is Parkinson’s Disease linked to?
Linked to 10 different gene mutations (affect mitochondria function)
63
What is the MPTP model of Parkinson’s Disease?
The case of Frozen Addicts (Lanston, 1985)
- Synthetic heroin produces the symptoms of Parkinson’s
- contained MPTP (neurotoxins)
64
What does MPTP cause?
Causes cell loss in the substantia nigra (like that seen in PD) → loss of dopaminergic cells leads to decline in dopamine
65
What does MPTP cause?
What did animals studies of the MPTP model find?
Animal studies led to the finding that deprenyl can slow down the progression of PD
66
Deprenyl
Is a monoamine agonist – blocks the effect of MPTP (slow down development)
67
Alzheimer’s Disease
```
Most common (but not only) cause of dementia – likelihood of developing it increases with age.
Pattern diffuse but more concentrated in medial temporal lobe structures (entohinal cortex, amygdala, hippocampus)
```
68
How is Alzheimer’s disease progressive?
Early stage: confusion and selective decline in memory
Intermediate stages: confusion anxiety, speech problems
Final stage: loss of control of functions
69
How is Alzheimer’s disease diagnosed?
Definitive diagnosis only at autopsy
- neurofibrillary tangles
- amyloid plaques (scar tissue)
- neuronal loss
70
What was the transgenic mice and Alzheumer’s disease study?
Transgenic – genes of another species have been introduced
Only humans and a few related primates develop emyloid plaques.
Genes accelerating human amyloid synthesis introduced into mouse eggs and implanted
- plaque distribution in transgenic mice comparable to that in AD, and associated memory problems observed
- No neurofibrillary tangles
71
What are the neuroplastic responses to damage?
1. Neural degeneration – deterioration
2. Neural regeneration – re-growth of damaged neurons
3. Neural reorganisation
4. Recovery of brain function
72
Types of Neural degeneration
Axtomoy
Anterograde
Retrograde
Transneuronal degeneration
73
Axtomoy of neural degeneration
Cutting axons
Method to study responses to neuronal damage
Cutting a neuron’s axon results in two forms of neural degeneration
- anterograde degeneration
- Retrograde degeneration
74
Anterograde neural degeneration
Distal portion of neuron degenerates quickly
75
Retrograde Neural degeneration
Proximate portion of the neuron may degenerate o regenerate slowly (depending on reaction of cell body)
76
Transneuronal degeneration neural degeneration
Degeneration transmitted from damaged neurons to intact neurons via synaptic connections
77
Neural regeneration
Not successful in mammals and other higher vertebrates – capacity for accurate axonal growth is lost in maturity
Regeneration is virtually non-existent in the CNS of adult mammals and unlikely, but possible, in the PNS
78
How does regeneration in the PNS start?
Re-growth starts 2-3 days after injury.
79
How does regeneration occur when the schwann cells myelin sheath is intact?
Regeneration axons may grow through them to their original targets (mm per day).
80
How does regeneration occur when the nerve Is severed and the ends are separated?
They may grow into incorrect sheaths toward incorrect destinations
81
How does regeneration occur when the ends of the neurons are widely separated?
No meaningful regeneration will occur
82
Why do mammalian CNS neurons regenerate in the PNS?
CNS neurons can regenerate if transplanted into the PNS, while PNS neurons will not regenerate in the CNS → PNS environment
83
How do Schwann cells (PNS) promote regeneration?
Schwann cells (PNS) promote regeneration through
- neurotrophic factors – stimulate new axon growth
- CAMs (Cell Adhesion Molecules) – provide a pathway
84
How do oligodendroglia (CNS) promote regeneration?
Oliodendroglia release substances actively blocking regeneration
85
Neural reorganisation?
Reorganisation of the primary sensory and motor systems has been observed following damage to:
- peripheral nerves
- primary cortical areas
86
What is the animal example of neural reorganisation?
Lesion one retina and removal of other – V1 neurons that originally respond to lesioned area now responded to an adjacent area – remapping occurred within minutes
87
What is the human example of neural reorganisation?
Imaging studies with blind patients – auditory and somatosensory cortex is comparatively larger (Elbert er al., 2002) – superior performance on relevant tasks compared to sighted individuals (Gougoux et al., 2005)
88
How/why does damage lead to reorganisation?
Two possible mechanisms:
1. Strengthened existing connections (release from inhibition?) – consistent with speed and localised nature of recognition)
2. establishment of new connections – Collateral sprouting – magnitude can be too great to be explained by changes in existing connections
89
What is the two-stage model of neural reorganisation?
1. Release from inhibition strengthens existing connections
| 2. Collateral sprouting results in new connections
90
How does recovery occur of CNS function?
Poor understood
Almost non-existent
Difficult to differentiate between compensation and true recovery (e.g. improvements due to reduction in brain swelling after injury)
Role of cognitive reserve?
Neurotransplantation (implantation of embryonic tissue/stem cells/injection of targeted versus/growth factors
Rehabilitative training
