Module 4.2 & 4.3 Flashcards
Kennard Principe
- Recovery is generally more extensive after youthful brain damage than after similar damage later
But, young brain is also more vulnerable, so it’s not always a given
Closed head injury (CHI)
- Sudden, sharp blow to the head that does not puncture the brain, e.g., an automobile accident or assault
Stroke
- A loss of blood flow
- Ischemia (aka cerebrovascular accident) - (when a blood clot or other obstruction blocks an artery)
- hemorrhage (when an artery ruptures) causing a loss of normal blood flow to a brain area
–> a chain of chemical events results in accumulation of sodium, calcium and zinc ions inside neurons, causing cell death
–> Cells in the immediate area die quickly, but cells further away (in the PENUMBRA, or region surrounding immediate damage) have some time and may be saved with intervention – how?
Penumbra
The region around the damaged area of the brain
Possible solutions for a hemorrhage
Surgery
Rest
Possible solutions for stroke
- Most effective thing so far is cooling the brain – a cooled brain has less activity and fewer energy needs, so can survive on less (91-97 degrees F for about the first 3 days after stoke)
- Injecting neurotrophins and other drugs that block apoptosis
- Tissue Plasminogen Activator (TPA)
- Acts like draino and busts things up and can be used for ischemias
Effects of Age on Recovery [placeholder]
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Mechanisms of Recovery After Brain Damage
- Most recovery occurs in the first month after the damage, at about 9 months out, you typically don’t get much more recovery
- Even at best, brain typically isn’t exactly as it was before
- Learned adjustments in behavior – making better use of what’s left
–> Learned adjustments in behavior – making better use of what’s left
Diaschisis
- What you are worried about in the penumbra
- The decreased activity of the neurons that survived
Stimulant Drugs
Stimulant drugs paired with physical therapy enhanced the recovery of stroke victims suffering from diaschisis, the decreased activity of surviving neurons
Regrowth of axons
- axons in peripheral NS can regrow but may reattach to the wrong muscle
- It regrows at the rate of about 1 mm per day, so slow!
- In mature mammals, damaged axons usually regenerate no more than a mm or two, so many injuries are permanent (paralysis)
- But CNS and peripheral axons regrow in fish
- Unfortunately, scar tissue, astrocytes, and myelin secrete proteins that inhibit regrowth in humans
Two Mechanisms of Recovery After Brain Damage [placeholder]
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Collateral Sprouting
- after damage to a set of axons, the postsynaptic cells secrete neurotrophins that induce nearby uninjured axons to form new branches to replace the damaged ones
- The postsynaptic cell asks the surviving presynaptic cell for help
Denervation or disuse supersensitivity
- What the postsynaptic cell does this help itself
- Cells have died or are in disuse because they are injured or inactive
- after the destruction or inactivity of an incoming axon, the postsynaptic cell becomes more sensitive to a neurotransmitter (so it can be affected by NT submitted further away from surviving axons)
- It can also increase the number of receptors
- remaining neurons also increase the release of neurotransmitter
- Change the shape of the receptors so its a better fit (affinity)
Behavioral Interventions
Current emphasis is on supervised practice of impaired skills
Positive reinforcement therapy helps develop socially acceptable behavior for persons with frontal lobe therapy
Research suggests therapists remove distracting stimuli and help person develop remaining skills
Often people don’t want to learn how to use their damaged body part – it’s hard and uncomfortable and can be painful, so they’d rather work around it – therapists help push them to use it
Drugs
Nimodipine (calcium blocker) improved memory on visual learning tasks
–> in rats with visual cortex lesions
–> Presumably by preventing a toxic rush of calcium into neurons
Gangliosides (carbohydrate and fat molecules) help restore damaged brains
–> through unknown mechanisms
- Women with brain injury recover better than men and especially if the damage occurs when progesterone levels were high – why? We don’t know
Brain Grafts
- Neural transplants have been tried to treat Parkinson’s disease with limited success
- Difficulties include finding suitable donor cells (here’s where the stem cell debate comes in)
- Currently experimental and controversial
Growth and Differentiation of the Brain [placeholder] {info dump}
- CNS begins to form when embryo is two weeks old
- By 7 weeks the hindbrain, midbrain and forebrain are differentiated
- At birth, brain weighs 350g
- About 9 months after birth the prefrontal cortex is developed enough for child to achieve “object permanence”
- At end of first year brain weighs 1000 grams, close to adult weight of 1200-1400 grams
Object Permanence
a child’s ability to know that objects continue to exist even though they can no longer be seen or heard.
Growth and Development of Neurons [placeholder]
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5 processes involved in the development of our neurons
proliferation, migration, differentiation, myelination, and synaptogenesis
Proliferation
the production of new cells – how? cells in the ventricles divide
- some stay as stem cells – just keep dividing and making new cells
- some become primitive neurons and glia that go to new destinations
Migration
cells follow chemical path toward final destination
- Gene or poison that interferes with proliferation or migration can produce intellectual disability
Differentiation
turning the primitive neuron into a real neuron
- axons and dendrites are formed.
Axon grows first – that happens during migration - Dendrites typically form after it reaches its final location
Myelination
- addition of an insulating sheath that speeds transmission
- Glia cells produce the myelin – what type?
Synaptogenesis
- formation of synapses continues throughout life
- Cholesterol is essential for synapse formation (why you don’t want to be too low, either)
Determinants of Neuron Survival [placeholder] {info dump}
- Neurons aren’t random – every single neurons has a job and a place – its dendrites must receive info in the right area and its axon must send the info to the right area – how does a developing brain know how to organize this??
- We originally produce WAY more neurons than we need, to be sure we have enough of what we need
- Each new neuron start its life with a “suicide program:” it knows if its axon doesn’t make contact with an appropriate postsynaptic cell, it needs to kill itself
- The killing of itself is called apoptosis – a programmed mechanism of cell death
apoptosis
a programmed mechanism of cell death
Survival requires two conditions
- must form synapse with target cell and receive a protein called nerve growth factor (NGF) from that cell. NGF cancels apoptosis – it says, “don’t kill yourself.”
- must also be stimulated to release neurotransmitters into synapse
- Apoptosis occurs when synapses receive too little NGF
- Competition among neurons for survival is a selection process that has been termed neural Darwinism
Chemical Pathfinding by Axons
Axons seek specific connections
- Weiss: axons from normal leg branched to corresponding muscles of grafted leg
- Sperry: cut axons from optic nerve to vision area and then rotated eye of newt, but axons returned to their original site
Axons follow chemical gradients
- In newt, a chemical named TOPDV is concentrated more in the dorsal than ventral retina, and more in the ventral than dorsal vision area
—> axons from retina follow paths to sites on vision area with similar TOPDV concentrations
Fine-Tuning by Experience [placeholder]
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How exactly does our brain know how to develop?
- We’re born with genetic instructions that get us started
- Our experiences actually change our brains – the fact that our brains are changeable is why we refer to our brains as “plastic” or having “plasticity”
Experience alters dendritic branching
- enriched environments and exercise increases branching and develops thicker cortex
- Exercise also releases neurotrophins – the idea that exercise is good for your brain is really true!
- education also correlated with branching
Generation of New Neurons [placeholder}
Current state of knowledge: except for olfactory and perhaps hippocampal neurons, new neurons do not form in adult human brains
Effects of Experience on Human Brain Structure
- First, axons find their targets by following chemicals
- Then they strengthen and discard some connections in response to experience
Ex: Professional musicians have enlarged area in temporal cortex of right hemisphere (auditory area) (but is it the chicken or the egg?)
- Extensive experience with stringed instruments enlarges and reorganizes area of post central gyrus devoted to left fingers
Proportional Growth of Brain Areas
- Size of one area proportional to others – animals with one larger part of the brain than other animals will likely have all other areas of the brain larger (except olfactory bulb is smaller in humans than most other mammals!)
- Brain structure related to way of life. Monkeys swing through trees and so have larger brain representation of their forearm muscles
The Vulnerable Developing Brain
Developing brain more vulnerable to effects of malnutrition, toxic chemicals and infections than older brain
- anesthesia can kill neurons in infants
- child of diabetic mother may have long-term attention and memory problems
Fetal alcohol syndrome at birth
- severe health and mental health problems, e.g., heart defects, facial abnormalities, hyperactivity and depression, varying degrees of intellectual disability
- Their dendrites tend to be short, with few branches
- neurons received fewer neurotrophins, resulting in increased apoptosis
