Question | Answer |
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. |