Module 4.2 & 4.3

Question 1

Kennard Principe

Answer 1

• 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

Question 2

Closed head injury (CHI)

Answer 2

• Sudden, sharp blow to the head that does not puncture the brain, e.g., an automobile accident or assault

Question 3

Stroke

Answer 3

• 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?

Question 4

Penumbra

Answer 4

The region around the damaged area of the brain

Question 5

Possible solutions for a hemorrhage

Answer 5

Surgery
Rest

Question 6

Possible solutions for stroke

Answer 6

• 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

Question 7

Effects of Age on Recovery [placeholder]

Answer 7

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Question 8

Mechanisms of Recovery After Brain Damage

Answer 8

• 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

Question 9

Diaschisis

Answer 9

• What you are worried about in the penumbra
• The decreased activity of the neurons that survived

Question 10

Stimulant Drugs

Answer 10

Stimulant drugs paired with physical therapy enhanced the recovery of stroke victims suffering from diaschisis, the decreased activity of surviving neurons

Question 11

Regrowth of axons

Answer 11

• 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

Question 12

Two Mechanisms of Recovery After Brain Damage [placeholder]

Answer 12

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Question 13

Collateral Sprouting

Answer 13

• 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

Question 14

Denervation or disuse supersensitivity

Answer 14

• 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)

Question 15

Behavioral Interventions

Answer 15

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

Question 16

Drugs

Answer 16

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

Question 17

Brain Grafts

Answer 17

• 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

Question 18

Growth and Differentiation of the Brain [placeholder] {info dump}

Answer 18

• 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

Question 19

Object Permanence

Answer 19

a child’s ability to know that objects continue to exist even though they can no longer be seen or heard.

Question 20

Growth and Development of Neurons [placeholder]

Answer 20

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Question 21

5 processes involved in the development of our neurons

Answer 21

proliferation, migration, differentiation, myelination, and synaptogenesis

Question 22

Proliferation

Answer 22

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

Question 23

Migration

Answer 23

cells follow chemical path toward final destination

• Gene or poison that interferes with proliferation or migration can produce intellectual disability

Question 24

Differentiation

Answer 24

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

Question 25

Myelination

Answer 25

- addition of an insulating sheath that speeds transmission - Glia cells produce the myelin – what type?

Question 26

Synaptogenesis

Answer 26

- formation of synapses continues throughout life - Cholesterol is essential for synapse formation (why you don’t want to be too low, either)

Question 27

Determinants of Neuron Survival [placeholder] {info dump}

Answer 27

- 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

Question 28

apoptosis

Answer 28

a programmed mechanism of cell death

Question 29

Survival requires two conditions

Answer 29

- 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

Question 30

Chemical Pathfinding by Axons

Answer 30

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

Question 31

Fine-Tuning by Experience [placeholder]

Answer 31

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Question 32

How exactly does our brain know how to develop?

Answer 32

- 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”

Question 33

Experience alters dendritic branching

Answer 33

- 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

Question 34

Generation of New Neurons [placeholder}

Answer 34

Current state of knowledge: except for olfactory and perhaps hippocampal neurons, new neurons do not form in adult human brains

Question 35

Effects of Experience on Human Brain Structure

Answer 35

- 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

Question 36

Proportional Growth of Brain Areas

Answer 36

- 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

Question 37

The Vulnerable Developing Brain

Answer 37

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

Question 38

Fetal alcohol syndrome at birth

Answer 38

- 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