Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats

Thomas Pang Lo, Kyoung Suok Cho, Maneesh Sen Garg, Michael Patrick Lynch, Alexander Eduardo Marcillo, Denise Leigh Koivisto, Monica Stagg, Rosa Marie Abril, Samik Patel, W. Dalton Dietrich, Damien Daniel Pearse

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

Hypothermia has been employed during the past 30 years as a therapeutic modality for spinal cord injury (SCI) in animal models and in humans. With our newly developed rat cervical model of contusive SCI, we investigated the therapeutic efficacy of transient systemic hypothermia (beginning 5 minutes post-injury for 4 hours, 33°C) with gradual rewarming (1°C per hour) for the preservation of tissue and the prevention of injury-induced functional loss. A moderate cervical displacement SCI was performed in female Fischer rats, and behavior was assessed for 8 weeks. Histologically, the application of hypothermia after SCI resulted in significant increases in normal-appearing white matter (31% increase) and gray matter (38% increase) volumes, greater preservation (four-fold) of neurons immediately rostral and caudal to the injury epicenter, and enhanced sparing of axonal connections from retrogradely traced reticulospinal neurons (127% increase) compared with normothermic controls. Functionally, a faster rate of recovery in open field locomotor ability (BBB score, weeks 1-3) and improved forelimb strength, as measured by both weight-supported hanging (43% increase) and grip strength (25% increase), were obtained after hypothermia. The current study demonstrates that mild systemic hypothermia is effective for retarding tissue damage and reducing neurological deficits following a clinically relevant contusive cervical SCI.

Original languageEnglish (US)
Pages (from-to)433-448
Number of pages16
JournalJournal of Comparative Neurology
Volume514
Issue number5
DOIs
StatePublished - Jun 10 2009

Keywords

  • Axon sparing
  • Cooling
  • Forelimb function
  • Neuroprotection
  • Reticulospinal
  • Spinal cord injury
  • Tissue loss

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

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    Lo, T. P., Cho, K. S., Garg, M. S., Lynch, M. P., Marcillo, A. E., Koivisto, D. L., Stagg, M., Abril, R. M., Patel, S., Dietrich, W. D., & Pearse, D. D. (2009). Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats. Journal of Comparative Neurology, 514(5), 433-448. https://doi.org/10.1002/cne.22014