Beneficial effects of modest systemic hypothermia on locomotor function and histopathological damage following contusion-induced spinal cord injury in rats.
OBJECTIVE
Local spinal cord cooling (LSCC) is associated with beneficial effects when applied following ischemic or traumatic spinal cord injury (SCI). However, the clinical application of LSCC is associated with many technical difficulties such as the requirement of special cooling devices, emergency surgery, and complicated postoperative management. If hypothermia is to be considered for future application in the treatment of SCI, alternative approaches must be developed. The objectives of the present study were to evaluate 1) the relationship between systemic and epidural temperature after SCI; 2) the effects of modest systemic hypothermia on histopathological damage at 7 and 44 days post-SCI; and 3) the effects of modest systemic hypothermia on locomotor outcome at 44 days post-SCI.


METHODS
A spinal cord contusion (12.5 mm at T-10) was produced in adult rats that had been randomly divided into two groups. Group 1 rats (seven in Experiment 1; 12 in Experiment 2) received hypothermic treatment (epidural temperature 32-33 degrees C) 30 minutes postinjury for 4 hours; Group 2 rats (nine in Experiment 1; eight in Experiment 2) received normothermic treatment (epidural temperature 37 degrees C) 30 minutes postinjury for 4 hours. Blood pressure, blood gas levels, and temperatures (epidural and rectal) were monitored throughout the 4-hour treatment period. Twice weekly assessment of locomotor function was performed over a 6-week survival period by using the Basso-Beattie-Bresnahan locomotor rating scale. Seven (Experiment 1) and 44 (Experiment 2) days after injury, animals were killed, perfused, and their spinal cords were serially sectioned. The area of tissue damage was quantitatively analyzed from 16 longitudinal sections selected from the central core of the spinal cord.


CONCLUSIONS
The results showed that 1) modest changes in the epidural temperature of the spinal cord can be produced using systemic hypothermia; 2) modest systemic hypothermia (32-33 degrees C) significantly protects against locomotor deficits following traumatic SCI; and 3) modest systemic hypothermia (32-33 degrees C) reduces the area of tissue damage at both 7 and 44 days postinjury. Although additional research is needed to study the therapeutic window and long-term benefits of systemic hypothermia, these data support the possible use of modest systemic hypothermia in the treatment of acute SCI.
Yu
C G
CG
The Miami Project, and Department of Neurological Surgery, University of Miami, Florida, USA.
Jimenez
O
O
Marcillo
A E
AE
Weider
B
B
Bangerter
K
K
Dietrich
W D
WD
Castro
S
S
Yezierski
R P
RP
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood; D003288:Contusions / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D004824:Epidural Space / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D007036:Hypothermia, Induced; D008124:Locomotion / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000502:physiology; D013116:Spinal Cord / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D020760:Spinal Cord Ischemia / Q000628:therapy; D016896:Treatment Outcome
D002245:Carbon Dioxide; D010100:Oxygen