Neuroprotection following mild hypothermia after spinal cord ischemia in rats

Objective: We examined the hypothesis that a 1 C reduction in body temperature would reduce gray and white matter injury induced by spinal cord ischemia in rats. In addition, we evaluated the relationship between reactive astrogliosis and gray or white matter injury after spinal cord ischemia with a 1 C reduction in body temperature or normothermia. Methods: Rats were randomly divided into hypothermia (1 C decrease in body temperature to 36.3 degrees C), normothermia (37.3 degrees C), and sham surgery groups (n = 6/group). Hypothermia was induced 15 minutes before ischemia and maintained during ischemia. Animals were then rewarmed to normothermia. Spinal cord ischemia was induced by a balloon catheter in the thoracic aorta, and the proximal mean arterial blood pressure was maintained at 40 mm Hg for 14 minutes. Hind limb motor function was assessed at 2, 7, 14, 21, and 28 days after reperfusion. At 28 days after reperfusion, gray matter damage was assessed by counting the number of normal motor neurons and white matter damage by the extent of vacuolation. The glial fibrillary acidic protein (GFAP)-positive area fraction (GFAP%) was determined in white and gray matter structures to measure reactive astrogliosis. Results: Compared with normothermia, hypothermia significantly improved hind limb function at all assessments (P < .01) and increased numbers of normal gray matter motor neurons (39 +/- 20 vs 99 +/- 13, respectively; P < .001), decreased the percentage area of white matter vacuolation (9.0% +/- 2.7% vs 1.6% +/- 1.3%, respectively; P = .001), and decreased the GFAP% in gray (P = .003) and white matter (P = .009). Conclusions: Prophylactic mild hypothermia (1 C reduction in body temperature) preserved hind limb motor function and reduced neuronal death, white matter vacuolation, and astrogliosis in gray and white matter induced by spinal cord ischemia in rats. Thus, mild hypothermia may be useful for perioperative management of thoracoabdominal aortic surgery. (J Vasc Surg 2013;57:173-81.) Clinical Relevance: Hypothermia (3 degrees-4 degrees C decrease in temperature) is known to protect the spinal cord from ischemia-reperfusion injury; however, hypothermia can also cause serious secondary complications. In this study, a 1 degrees C reduction in body temperature induced before spinal cord ischemia provided marked and persisting neuroprotection and reduced gliosis, without adverse effects. These data suggest that very mild hypothermia may be applied clinically to avoid systemic complications.