title: The role of directly applied hypothermia in spinal cord injury.
abstract: METHODS
  The effect of intense local hypothermia was evaluated in a precision model of spinal canal narrowing and spinal cord injury in rats. The spinal cord injury was cooled with a custom cooling well used over the epidural surface. Basso, Beattie, and Bresnahan (BBB) motor scores and transcranial magnetic motor-evoked potential (tcMMEP) responses were used after injury to accurately evaluate neurologic recovery.
  
  
  OBJECTIVE
  This study was undertaken to determine whether the prognosis for neurologic recovery in a standardized rat spinal cord injury model is altered by the direct application of precisely controlled hypothermia to the area of injury.
  
  
  BACKGROUND
  The role of hypothermia in the treatment of spinal cord injuries with neurologic deficits remains undefined. Hypothermia may decrease an area of spinal cord injury and limit secondary damage, therefore improving neurologic recovery. However, it has been difficult to consistently apply localized cooling to an area of spinal cord injury, and the use of systemic hypothermia is fraught with complications. This fact, along with the unavailability of a precise spinal cord injury model, has resulted in inconsistent results, both clinically and in the laboratory. In a rat model of spinal cord injury, 37 C and 19 C temperatures were used to study the role of hypothermia on neurologic recovery.
  
  
  METHODS
  Male Spraque-Dawley rats (n = 52; weight, 277.7 g) were anesthetized with pentobarbital and subjected to laminectomy at T10. The rats were divided into three groups: 1) placement of a 50% spacer in the epidural space (16 rats), 2) severe (25 g/cm) spinal cord injury (16 rats), 3) 50% spacer in combination with spinal cord injury (16 rats). Eight rats in each group were tested at two temperatures: normothermic (37 C) and hypothermic (19 C). With the use of a specially designed hypothermic pool placed directly over the spinal cord for 2 hours, epidural heating to 37 C, and epidural cooling to 19 C was accomplished. Simultaneous measurements of spinal cord and body temperatures were performed. The rats underwent behavior testing using the BBB motor scores and serial tcMMEPs for 5 weeks. Statistical methods consisted of Student's t tests, one-way analysis of variance, Tukey post hoc t tests and chi2 tests.
  
  
  RESULTS
  There was a significant improvement in motor scores in rats subjected to hypothermia compared with those that were normothermic after insertion of a 50% spacer. This improvement was observed during the 5-week duration of follow-up. In the severe spinal cord injury group and the spinal cord injury-spacer groups, no significant improvement in motor scores were obtained when the spinal cord was exposed to hypothermia.
  
  
  CONCLUSIONS
  The results demonstrate that there is a statistically significant (P < 0.05) improvement in neurologic function in rats subjected to hypothermia (19 C) after insertion of a spacer that induced an ischemic spinal cord injury. This indicates that directly applied hypothermia may be beneficial in preventing injury secondary to ischemic cellular damage. The data demonstrated minimal therapeutic benefit of hypothermia (19 C) after a severe spinal cord injury.
authors.affiliation: Departments of Orthopaedic Surgery and Neurological Surgery, University of Louisville, and the Kenton D. Leatherman Spine Center, Louisville, Kentucky 40202, USA. SiSS001@aol.com
authors.forename: J R
authors.initials: JR
authors.lastname: Dimar
authors.forename: C B
authors.initials: CB
authors.lastname: Shields
authors.forename: Y P
authors.initials: YP
authors.lastname: Zhang
authors.forename: D A
authors.initials: DA
authors.lastname: Burke
authors.forename: G H
authors.initials: GH
authors.lastname: Raque
authors.forename: S D
authors.initials: SD
authors.lastname: Glassman
mesh_terms: D000818:Animals; D001831:Body Temperature; D001835:Body Weight; D019054:Evoked Potentials, Motor; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013115:Spinal Canal / Q000293:injuries; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy*; D013130:Spinal Stenosis / Q000628:therapy*