9/1 Trauma - Crockett Flashcards
male : female risk of spinal cord injury
2 : 1 (M : F)
males most risk bw 20-30yrs and 70+
females most risk bw 15-19yrs and 60+
inflammatory response to spinal cord injury
- microglia: active from minutes to years
- neutrophils : active in mins/hrs/days range
- monoctyes: active in days-years range
- lymphocytes: active in days-months range
response types:
microglial activation
- go from ramified → amoeboid
- (opp of polarization)
- release pro-infl cytokines AND anti-infl cytokines
infl response and neuropathic pain
activated microglia linked to neuropathic pain
tx: rapaycin
- reduces microglia and pain sensitivity following spinal cord injury
- no effect on astrocytic response to injury
systemic effects of chronic inflammation
- metabolic changes
- hematopoetic changes
- neuroendocrine changes
systemic effects of chronic inflammation
metabolic changes
- metabolic changes
- loss of muscle and negative nitrogen balance
- decreased gluconeogenesis
- osteoporosis
- increased hepatic lipogenesis
- increased lypolysis in adipose tissue
- decreased LPL activity in muscle and adipose tissue
- cachexia
systemic effects of chronic inflammation
hematopoetic changes
- hematopoetic changes
- anemia of chornic disease
- leukocytosis (high WBC count)
- thrombocytosis (high platelet count)
systemic effects of chronic inflammation
neuroendocrine changes
- neuroendocrine changes
- fever, somnolence, anorexia
- increased secretion of CRH, corticotropin, and cortisol
- increased secretion of AVP
- decreased production of IGF1
- increased adrenal secretion of catecholamines
- impaired growth
- reduced testosterone
clinical management of spinal cord injury
management
surgical intervention
- methylprednisolone
- controversial : mixed results, not recommended
- erythropoietin (EPO)
- controversial : mixed results
- minocycline
- some success (modulates immune response); ongoing clinical trials
surgical advances include:
- decompression/stabilization of spine
- management of syringomyelic cysts
- peripheral nerve bridging
- implanting avulsed roots/nerves into SC
spinal cord injury sequelae
- tissue disruption (primary cell death, breaking of axons)
- progressive tissue loss
- central hemorrage necrosis over 2-3 hours
- white matter blood flow drops by 50% in 3 hrs
- metabolism compromised with high lactic acid levels
role of calcium in SCI sequelae
rapid entry of Ca into cells causes swelling
- intracellular Ca activity activates proteases and phospholipases (breaking down proteins/lipids)
Ca binds to mitochondria and produces free radicals (cytotoxic)
cell death & “hostile environment” in SCI
cell death
- neuronal apoptosis peaks at 48hr in gray matter around injury site
- oligodendroglial apoptosis peaks at 10-14d in degenerating white matter tracts
hostile environement
- breakdown of bbb
- rapid pro-infl cytokine response (<1hr)
- IL-1a,-1b,-6,TNF alpha
- peak at 6hr, down to baseline by 24hr
- activation of microglia and macrophages
- reactive astrocytes and gliosis (glial scar)
- expression of inhibitory molecules
nervous system response to injury
neurons don’t grow back
it that because of the neurons or glia???
neurons of peripheral nervous system CAN regenerate
neurons of central nervous system CANNOT regenerate
possible explanation: diffs in glial cells!
- PNS glial cells = Schwann cells
- CNS glial cells = oligodendrocytes
evidence for this theory: CNS neurons will regenerate through a transplant of Schwann cells
inhibitory factors in glial scar
(incomplete list)
- cellular debris
- degenerating myelin (myelin basic protein)
- myelin associated inhibitory factors
- Nogo A
- MAG (myelin-assoc glycoprotein)
- OMgp (oligodendrocyte myelin glycoprotein)
- chrondoitin sufate proteoglycans (CSPG)
- proteoglycans
- versican V2
- brevican
- NG2
- tenascin-R
Nogo
released by broken myelin
when Nogo binds to its receptor → inhibitory in action
- axon fails to grow
experiment: deactivation of Nogo A leads to long-distance regeneration and functional recovery in rats treated with anti-Nogo antibodies
mesenchymal stem cells
potent connective tissue regen cells possessing both local and systemic immununomodulatory fx
- SCI models → MSCs are neuroprotective
- transplants in animals have produced positive results
