Recovery of Function

Recovery

Ability to achieve functional goals in the same or similar ways as they were performed before the injury

Compensation

Behavioral substitution

- Individual performs a task in a different way than was done before injury

Sparing of Function

When a function is not lost despite a brain injury

Vicarious Function Theory

Assumes that function attributed to the damaged portion of the nervous system can be learned, or taken over, by areas not previously concerned with the function

CNS Redundancy Theory

CNS has back-up systems that become operational when the primary system breaks down

- Unmasking of the new (redundant) pathways maintain function

Functional Substitiution

Areas of the brain become reprogrammed

Wallerian (anterograde) Degeneration

Degeneration of the distal segment separated from the proximal axonal segment

Retrograde Degeneration

Degeneration of the proximal portion of the axon

Inflammation spreads from site of injury to the SC to at least ___ segments away within ___ hour of injury?

10, 24

Excitotoxicity

Excessive release of glutamate, dopamine, and norepinephrine following CNS injury creates toxic environment that leads to neuronal death

Apoptosis

Programmed cell death

- Activation of caspases triggered by neural damage can lead to cell death

Oxidative and Nitrosative Stress

Neural injury causes increase of reactive oxygen species (ROS) and reactive nitrogen species (RNS aka free radicals) which are detrimental to neurons

Diaschisis

Neural shock resolution (reflexes will go from absent to hyperreflexive)

Angiogenesis

Formation of new blood vessels

Neurogenesis

Formation of new neurons

M1 Microglia

Release inflammatory factors and toxic substances that induce inflammation and neurotoxicity

- M1 bad/inflammation

M2 Microglia

Get rid of debris and dead tissue/express anti-inflammatory molecules

- Promotes blood/brain barrier repair, neurogenesis, astrogenesis

- M2 good/anti-inflam

A1 Astrocyte

Produce pro-inflammatory substances and neurotoxins that can kill neurons and oligodendrocytes

- Pro inflam

A2 Astrocyte

Rush to site of CNS injury, restoring blood flow and forming scar to limit spread of inflammation

- Anti inflam

M2 Microglia and A2 astrocytes and neurons release neurotrophic factors in response to ischemia such as: ___ (3)?

1. Brain-derived neurotrophic factor (BDNF)

2. Insulin-like growth factor 1 (IGF-1)

3. Nerve growth factor (NGF)

What do neurotrophic facotrs promote?

- Cell survival

- Strengthen synaptic connections

- Axonal growth and sprouting

Diaschisis: Cause

Loss of function in a structurally intact brain area d/t loss of input from an anatomically connected area that is injured

Neural Shock d/t Diaschisis

Short term loss of function near and far from the lesion site

- Over time the intact area recovers from loss of afferent inputs and symptoms usually resolve

Synaptic Effectiveness During Acute CNS Injury

Neurons at site of lesion may not function d/t compression of axons by edema or disruption of blood supply

- Once edema resolves and blood supply restored, function may be restored (used to explain return of tone in initially flaccid paralysis)

Synaptic Hypereffectiveness

When one or more branches of a presynaptic axon are destroyed the remaining axon branches release a larger than normal amount of NTs onto postsynaptic receptors

Denervation Sensitivity

An increase in the number of postsynaptic receptors or enhanced responsiveness of remaining receptors may allow limited NT input to drive postsynaptic neurons thereby restoring function

Axonal Regeneration

Sprouts from injured axons start growing to form new synapses within several days

Rate of Axonal Regeneration in the PNS

Occurs at a rate of 1 mm/day

Collateral Sprouting

Occurs when axons of nearby uninjured neurons sprout branches that synapse at sites vacated by injured axons

When/Where does angiogenesis occur after stroke?

New blood vessels form in the peri-infarct zone in the first days to weeks after stroke

Penumbra

Surrounding area of injury becomes impaired but not dead

- Capable of recovery

Rapidity of Onset of Lesion Impact

Slow growing lesions such as tumors produce less profound effect that a sudden insult such as a stroke

How does age impact severity of lesion according to Kennard?

CNS injury sustained in infancy often produces fewer and less severe effects than does the same lesion in an adult nervous system

How does age impact severity of lesion according to Hebb?

Early damamge may be worse if it prohibits neural/behavioral development

Women vs Men Outcomes Post-Stroke

Women have poorer outcomes

Rx for Post-Stroke

- Dopamine increases outcomes

- Depressants decrease outcomes

Antisense Oligonucleotides

Hone in on genetic flaws and shit down their destructive effects by intercepting RNA