Combined Effect of Hypothermia and Hyperglycemia onTransient Focal Cerebral Ischemia of the Rat

ABSTRACT

BACKGROUND: In experimental cerebral ischemia, hypothermia protects the brain, while hyperglycemia aggravates ischemic damage. Clinical studies have also reported worse outcomes in ischemic stroke patients with hyperglycemia or fever and improved outcomes with hypothermic therapy. However, it is not well known what will happen if these opposite effects exist together. METHODS: Sixty male Sprague-Dawley rats were used. Focal cerebral ischemia was induced for 2 hours by an intraluminal thread followed by reperfusion for 4 hours. Rats were divided into 4 groups; 1) normo-glycemic normothermic (NGNT), 2) normoglycemic hypothermic (low temperature) (NGLT), 3) hyperglycemic normothermic (HGNT), and 4) hyperglycemic hypothermic (HGLT) groups (n=15 for each group). Hyperglycemia wasmade by intraperitoneal injection of streptozotocin (60 mg/kg) 3 days before ischemia. The body temperature was maintained at 37+/-1 degrees C in normothermic animals, while lowered at 32+/-1 degrees C in hypothermic animals during the ischemic period. Following reperfusion, 2-mm thick coronal slices were obtained and stained by triphenyltetrazolium chloride. The infarct volume was measured using an image analyzer. RESULTS: Mean glucose levels (mean+/-SD in mg/dl) were 77.9+/-9.3 in NGNT, 77.7+/-11.5 in NGLT, 311.0+/-69.2 in HGNT, and 355.3+/-57.7 in HGLT. Mean infarct volumes (mean+/-SD in mm 3) were 168.2+/-44.2 in NGNT, 66.2+/-24.2 in NGLT, 417.6+/-123.2 in HGNT, and 337.2+/-89.3 in HGLT. The protective effect of hypothermia was less evident in hyperglycemic rats and the aggravating effect of hyper-glycemia was more evident in hypothermic rats. Infarct volume of HGLT was 2-fold bigger than that of NGNT (p<0.05). CONCLUSIONS: Our results suggest that the detrimental effect of hyperglycemia may override the protective effect of hypothermia in transient focal cerebral ischemia.