Combined Effect of Hypothermia and Hyperglycemia on Transient Focal Cerebral Ischemia of the Rat Mei-Zi Jiang, M.D.*, Ja-Seong Koo, M.D.*, Byung-Woo Yoon, M.D.*, Jae-Kyu Roh, M.D.* Department of Neurology, Seoul National University College of Medicine* Neuroscience Research Institute in Medical Research Center, Seoul National University Department of Neurology, Affiliated Hospital of Yan Bian University College of Medicine, Jilin, China B a c k g r o u n d : 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) normoglycemic normothermic (NGNT), 2) normoglycemic hypothermic (low temperature) (NGLT), 3) hyperglycemic normothermic (HGNT), and 4) hyperglycemic hypothermic (HGLT) groups (n=15 for each group). Hyperglycemia was made by intraperitoneal injection of streptozotocin (60 mg/kg) 3 days before ischemia. The body temperature was maintained at 37±1in normothermic animals, while lowered at 32±1in 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. R e s u l t s : 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 hyperglycemia 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. J Korean Neurol Assoc 18(6):748~753, 2000 Key Words : Focal Cerebral Ischemia, Hyperglycemia, Hypothermia Byung-Woo Yoon, M.D. 748 Copyright 2000 by the Korean Neurological Association
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Table 1. Mean body weight in each group Normothermia (NT) Hypothermia (LT) Normoglycemia (NG) 265.0±36.0 255.3±33.3 Hyperglycemia (HG) 219.7±15.1* 231.3±24.2 Values are mean±sd (in gram). * p < 0.05 for HGNT vs NGNT and NGLT p < 0.05 for HGLT vs NGNT Table 2. Mean blood glucose level in each group Normothermia (NT) Hypothermia (LT) Normoglycemia (NG) 77.9±9.3 77.7±11.5 Hyperglycemia (HG) 311.0±69.2* 355.3±57.7* Values are mean±sd (in mg/dl). * p < 0.05 compared to normoglycemic (NG) groups Table 3. Mean volume of infarction (VOI) in each group Normothermia (NT) Hypothermia (LT) P values Normoglycemia (NG) 168.24±44.21 66.15±24.22 *p<0.01 Hyperglycemia (HG) 417.62±123.23 337.18±89.27 *p<0.05 P values p<0.01 p<0.01 p<0.01 Values are mean±sd (in mm 3 ). P values are for VOIs of each corresponding row (*) and column ( ). : P values for VOIs of NGNT and HGLT Figure 1. Comparisons of infarct volume in normoglycemic and hyperglycemic groups. Hypothermia reduced the infarct volume by 19.3% in hyperglycemic group and by 60.6% in normoglycemic group. NG ; normoglycemia, HG ; hyperglycemia, NT ; normothermia, LT ; hypothermia 750 J Korean Neurol Assoc / Volume 18 / November, 2000
Figure 2. Comparisons of infarct volume in normothermic and hypothermic groups. Hyperglycemia increased the infarct volume by 509.7% in hypothermic rats and by 248.2% in normothermic rats. NG; normoglycemia, HG; hyperglycemia, NT; normothermia, LT; hypothermia J Korean Neurol Assoc / Volume 18 / November, 2000 751
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