Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats.
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 degrees C) with gradual rewarming (1 degrees 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.
The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida 33101, USA.
Thomas Pang
TP
Lo
Kyoung-Suok
KS
Cho
Maneesh Sen
MS
Garg
Michael Patrick
MP
Lynch
Alexander Eduardo
AE
Marcillo
Denise Leigh
DL
Koivisto
Monica
M
Stagg
Rosa Marie
RM
Abril
Samik
S
Patel
W Dalton
WD
Dietrich
Damien Daniel
DD
Pearse
D000704:Analysis of Variance; D000818:Animals; D001933:Brain Stem / Q000473:pathology; D002470:Cell Survival; D002574:Cervical Vertebrae; D004195:Disease Models, Animal; D005260:Female; D007036:Hypothermia, Induced; D009043:Motor Activity; D053580:Muscle Strength; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways; D009474:Neurons / Q000473:pathology; D009929:Organ Size; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome
D009419:Nerve Tissue Proteins