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Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats
Authors:Thomas Pang Lo Jr  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
Affiliation:1. The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida 33101;2. The first two authors contributed equally to this work.;3. Uijongbu St. Mary's Hospital, Catholic University Medical College, Seoul, 480‐130 South Korea;4. Department of Neurology, University of Miami Miller School of Medicine, Miami, Florida 33101;5. Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida 33101;6. Department of Cell Biology and Anatomy, University of Miami, Miami, Florida 33101
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. J. Comp. Neurol. 514:433–448, 2009. © 2009 Wiley‐Liss, Inc.
Keywords:neuroprotection  spinal cord injury  cooling  axon sparing  tissue loss  reticulospinal  forelimb function
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