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Stack #215743

Neuro Unit II Lecture 10

What are the three basic types of spinal cord injury (SCI)? contusion, laceration, massive compression
What is another name for contusion? Bruising
A contusion to the spinal cord occurs without tearing what? pia or arachnoid
There are two types of contusions. What are they and what is the most common? Solid core: solid core of bruised tissue @ injury site. Cyst: fluid filled cyst @ site (MORE COMMON!)
What does laceration (in ref. to SCI) mean? cutting of sc/meninges as with a gunshot/knife wound
What does massive compression mean (in ref. to SCI)? compression of spinal cord due to breaking of vertebrae
What is the most common of the three basic types of SCI? What percent of all SCI is it? Contusion - 59%
Contusion injury has a particular progression. What is the first stage? Primary zone: area where cells mechanically destroyed. incr. Ca influx which causes release of excititory NT. This causes neurotoxicity where there is overstim. and a region of necrosis
Contusion injury has a particular progression. What is the second stage? Secondary Zone: after injury, area is partially preserved, but inflam & vascular damage causes ischemia/reduced bloodflow.
What happens to neurons during secondary zone of contusion progression? How long does this take to develop? Some neurons do apoptosis, others are stunned but survive. Takes hours/days to develop.
At what stage during contusion progression does research focus on and why. Secondary zone; focus on preserving living neurons and limiting damage
What is another name for secondary zone? penumbra
During secondary zone, what sometimes causes the appearance of a cyst/solid scar? What does the cyst contain? Astrocytes, progenitor cells, & microglia go to site of injury & differentiate to glial cells. Can get either a glial scar/cyst cavity containing CSF
What are the limited repair capabilities that are attempted with contusion? limited sprouting, degenerating mylinated axons phagocytosed, demylin surviving axons, some attempt regrowth (fail over long distances), new circuit formation (some to motor neurons using internerons), some spont. remylin, muscle atrophy
What happens to the reflex circuitry below the lesion? remains intact but with no communication w/brain
Which way to sensory neurons degenerate? What about motor neurons? Sensory toward brain (above lesion), motor toward periphery (below lesion)
What is wallerian (retrograde) degeneration? distal axons involved in lesion demylinate close to cell bodies first and then it moves back to their terminals
What are the two main things that occur during SCI repair? Spontaneous response and failed regrowth
Why does regrowth fail? Glial scar/cyst in the way or growth inhibiting factors are upregulated
What are the two growth inhibiting factors that are upregulated? Nogo-A, a myelin protein that is a axon guidance molecule and Chondroitin
What does Nogo-A normally do? It locks in axonal pathways in adults once the system is wired "THE GLUE!".
What does Nogo-A do in SCI patients? It is upregulated and inhibits axon regeneration
What does chondroitin do in SCI patients? stops sprouting and inhibs axonal regeneration.
What expresses Nogo-A? Is it in fetuses? oligodendricytes, after SCI, inhibiting axon regen, not in fetuses
What happens if you inject Nogo-A antibodies after SCI? enhance axon regrowth across injury & promote functional recovery, but absence of glial scaffold hinders regrowth through the lesion.
What does neuronal apoptosis in penumbra limit? repair of damaged circuitry
What are neruotrophins? A class of neurotropic factors. GSF's. Different neurons need different ones. They are very selective!
What is the main function of neurotrophins in the adult? to prevent cell death
What are the most well known neurotrophins? NGF, BDNF, NT-3, NT-4/5
What neurotrophins do ALL sensory neurons need? BDNF
What neurotrophin does Ia spindle fibers need? NT-3
What neurotrophin do nociceptors need? NGF
What do tract neurons, ie Clarkes nucleus, need to develop? NT-3
What neurotrophins do motor neurons need? BDNF and NT-3
After SCI, what needs to happen to repair function? Unglue the axons to allow them to survive and regrow (stop NOGO), Promote the survival of the axons, make the axons grow, and give them a scaffold to grow on
What are the things that promote the survival of the neurons and cause them to regrow? GSF's like neurotropins (a class of neurotropins is neurotrophins)
What secretes neurtotrophins? The target tissue
What things are involved in a neuron regrowing to a target? Attrations, repulsion, netrin
What are the two types of attractions? Contact mediated (nCAMs) - cell surface proteins that guide growth cone (drag neuron to target) and Chemotaxis mediated (Netrin-1)-secreted by target, forms a gradient in extracel environ.
What is involved in repulsion of a regrowing neuron? NOGO (contact mediated)- growth cone bounces off targets w/this. Chemotaxis mediated - Netrin-1 steers neurons away from it (like a bad odor), and Semaphorins - cell surface secreted proteins
What are netrins? The love/hate molecule; chemotatic effect can be both attractive and repulsive, depending on the axon (ie motor vs sensory, commis vs. CNIV)
What are the strategies of SCI tx? reduce cell death, clean up the mess, regrow axons, bridge the lesion, promote remylynation & axonal conduction, rehabilitate
What are the pluses of macrophage transplantation? What about the minuses? Pts own, clear up debris and make way for rebuilding. Negs: putting macros where they normally aren't/ highly controversal and questionable tx
Bridging the lesion: Can use two types to bridge: Tissue grafts (stem cells, transpl. perip. nerves, schwann cells, olfac. glial cells) or Synthetic implants (cell free, just the matrix, or cells - GF's +matrix molecules) Not in clinical trials yet
Functional electrical stimulation: computerized stim of muscles affected by lesion. Keeps muscles contracting. reproduce a bicycle type activity. prevent atrophy. activates sensory neurons at a reg. level of activity and slows degen of the circuits
What is the ultimate goal of SCI repair for motor? reestablish connections to motor nucl., remylin, reduce atrophy.
What is the ultimate goal of SCI repair for sensory? Start sprouting and growth of sensory axons, cross the bridge and reconnect with the axons on the other side of the lesion.
Created by: StudyBuddies