Moderate Posttraumatic Hypothermia Decreases Early Calpain-Mediated Proteolysis and Concomitant Cytoskeletal Compromise in Traumatic Axonal Injury

Moderate Posttraumatic Hypothermia Decreases Early Calpain-Mediated Proteolysis and Concomitant... Traumatic brain injury (TBI) in animals and man generates widespread axonal injury characterized by focal axolemmal permeability changes, induction of calpain-mediated proteolysis, and neurofilament side-arm modification associated with neurofilament compaction (NFC) evolving to axonal disconnection. Recent observations have suggested that moderate hypothermia is neuroprotective in several models of TBI. Nevertheless, the pathway by which hypothermia prevents traumatic axonal injury (TAI) is still a matter of debate. The present study was conducted to evaluate the effects of moderate, early posttraumatic hypothermia on calpain-mediated spectrin proteolysis (CMSP), implicated in the pathogenesis of TAI. Using moderate (32°C) hypothermia of 90 min duration without rewarming, the density of CMSP immunoreactive/damaged axons was quantified via LM analysis in vulnerable brain stem fiber tracts of hypothermic and normothermic rats subjected to impact acceleration TBI (90 min postinjury survival). To assess the influence of posthypothermic rewarming, a second group of animals was subjected to 90 min of hypothermia followed by 90 min of rewarming to normothermic levels when CMSP was analyzed to detect if any purported CMSP prevention persisted (180 min postinjury survival). Additionally, to determine if this protection translated into comparable cytoskeletal protection in the same foci showing decreased CMSP, antibodies targeting altered/compacted NF subunits were also employed. Moderate hypothermia applied in the acute postinjury period drastically reduced the number of damaged axons displaying CMSP at both time points and significantly reduced NFC immunoreactivity at 180 min postinjury. These results suggest that the neuroprotective effects of hypothermia in TBI are associated with the inhibition of axonal/cytoskeletal damage. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Experimental Neurology Elsevier

Moderate Posttraumatic Hypothermia Decreases Early Calpain-Mediated Proteolysis and Concomitant Cytoskeletal Compromise in Traumatic Axonal Injury

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Publisher
Elsevier
Copyright
Copyright © 1999 Academic Press
ISSN
0014-4886
D.O.I.
10.1006/exnr.1999.7139
Publisher site
See Article on Publisher Site

Abstract

Traumatic brain injury (TBI) in animals and man generates widespread axonal injury characterized by focal axolemmal permeability changes, induction of calpain-mediated proteolysis, and neurofilament side-arm modification associated with neurofilament compaction (NFC) evolving to axonal disconnection. Recent observations have suggested that moderate hypothermia is neuroprotective in several models of TBI. Nevertheless, the pathway by which hypothermia prevents traumatic axonal injury (TAI) is still a matter of debate. The present study was conducted to evaluate the effects of moderate, early posttraumatic hypothermia on calpain-mediated spectrin proteolysis (CMSP), implicated in the pathogenesis of TAI. Using moderate (32°C) hypothermia of 90 min duration without rewarming, the density of CMSP immunoreactive/damaged axons was quantified via LM analysis in vulnerable brain stem fiber tracts of hypothermic and normothermic rats subjected to impact acceleration TBI (90 min postinjury survival). To assess the influence of posthypothermic rewarming, a second group of animals was subjected to 90 min of hypothermia followed by 90 min of rewarming to normothermic levels when CMSP was analyzed to detect if any purported CMSP prevention persisted (180 min postinjury survival). Additionally, to determine if this protection translated into comparable cytoskeletal protection in the same foci showing decreased CMSP, antibodies targeting altered/compacted NF subunits were also employed. Moderate hypothermia applied in the acute postinjury period drastically reduced the number of damaged axons displaying CMSP at both time points and significantly reduced NFC immunoreactivity at 180 min postinjury. These results suggest that the neuroprotective effects of hypothermia in TBI are associated with the inhibition of axonal/cytoskeletal damage.

Journal

Experimental NeurologyElsevier

Published: Sep 1, 1999

References

  • Increased calpain content and progressive degradation of neurofilament protein in spinal cord injury
    Banik, N.L.; Matzelle, D.C.; Gantt-Wilford, G.; Osborne, A.; Hogan, E.L.
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    Bartus, R.T.; Dean, R.L.; Mennerick, S.; Eveleth, D.; Lynch, G.
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  • Effects of mild hypothermia on cerebral blood flow-independent changes in cortical extracellular levels of amino acids following contusion trauma in the rat
    Koizumi, H.; Fujisawa, H.; Ito, H.; Maekawa, T.; Di, X.; Bullock, R.
  • The effect of mild hyperthermia and hypothermia on brain damage following 5, 10, and 15 minutes of forebrain ischemia
    Minamisawa, H.; Smith, M.L.; Siesjo, B.K.
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    Morimoto, T.; Ginsberg, M.D.; Dietrich, W.D.; Zhao, W.
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    Okonkwo, D.O.; Pettus, E.H.; Moroi, J.; Povlishock, J.T.
  • Characterization of a distinct set of intra-axonal ultrastructural changes associated with traumatically induced alteration in axolemmal permeability
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  • Are the pathobiological changes evoked by traumatic brain injury immediate and irreversible
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