9/1 Trauma - Crockett Flashcards Preview

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Flashcards in 9/1 Trauma - Crockett Deck (15):
1

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+

2

inflammatory response to spinal cord injury

  1. microglia: active from minutes to years
  2. neutrophils : active in mins/hrs/days range
  3. monoctyes: active in days-years range
  4. 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

 

3

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

4

systemic effects of chronic inflammation

1. metabolic changes

2. hematopoetic changes

3. neuroendocrine changes

5

systemic effects of chronic inflammation

 

metabolic changes

1. 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

6

systemic effects of chronic inflammation

 

hematopoetic changes

2. hematopoetic changes

  • anemia of chornic disease
  • leukocytosis (high WBC count)
  • thrombocytosis (high platelet count)

7

systemic effects of chronic inflammation

 

neuroendocrine changes

3. 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

8

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

9

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

10

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)

11

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

12

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

13

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

14

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

15

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

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