Combined Effect of Hypothermia and Hyperglycemia on Transient Focal Cerebral Ischemia of the Rat

Size: px

Start display at page:

Download "Combined Effect of Hypothermia and Hyperglycemia on Transient Focal Cerebral Ischemia of the Rat"

Colin Neal
6 years ago
Views:

1 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

2 J Korean Neurol Assoc / Volume 18 / November,

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.

3 Table 1. Mean body weight in each group Normothermia (NT) Hypothermia (LT) Normoglycemia (NG) 265.0± ±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± ±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) ± ±24.22 *p<0.01 Hyperglycemia (HG) ± ±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

4 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,

5 01. Busto R, Dietrich WD, Globus MY-T, Valdes I, Scheinberg P, Ginsberg MD. Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab ; 7 : Busto R, Dietrich WD, Globus MY-T, Ginsberg MD. Postischemic moderate hypothermia inhibits CA1 hippocam- pal ischemic neuronal injury. Neurosci Lett 1989;101: Morikawa E, Ginsberg MD, Dietrich WD, Duncan RC, Kraydieh S, Globus MY-T, et al. The significance of brain temperature in focal cerebral ischemia: Histological consequences of middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 1992;12: Xue D, Huang Z-G, Smith KE, Buchan AM. Immediate or delayed mild hypothermia prevents focal cerebral infarction. Brain Res 1992;587: Dietrich WD, Busto R, Globus MY-T, Ginsberg MD. Brain damage and temperature: cellular and molecular mechanisms. In: Siesjo BK, Wieloch T. Adv Neurol Vol. 71. Philaselphia: Lippincott-Raven, 1996; Barone FC, Feuerstein GZ, White RF. Brain cooling dur- ing transient focal ischemia provides complete neuropro- 752 J Korean Neurol Assoc / Volume 18 / November, 2000

6 tection. Neurosci Biobehav Rev 1997;1: Reith J, Jorgensen HS, Pederson PM, Nakayama H, Raaschou HO, Jeppesen LL, et al. Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome. Lancet 1996;347: Fukuda H, Kitani M, Takahashi K. Body temperature correlates with functional outcome and the lesion size of cerebral infarction. Acta Neurol Scand 1999;100: Grau AJ, Buggle F, Schnitzler P, Spiel M, Lichy C, Hacke W. Fever and infection early after ischemic stroke. J Neurol Sci 1999;171: Schwab S, Spranger M, Aschoff A, Steiner T, Hacke W. Brain temperature monitoring and modulation in patients with severe MCA infarction. Neurology 1997;48: Schwab S, Schwarz S, Spranger M, Keller E, Bertram M, Hacke W. Moderate hypothermia in the treatment of patients with severe middle cerebral artery infarction. Stroke 1998;29: Siemkowicz E, Hansen AJ. Clinical restitution following cerebral ischemia in hypo-, normo-, and hyperglycemic rats. Acta Neurol Scand 1978;58: Pulsinelli WA, Waldman S, Rawlinson D, Plum F. Moderate hyperglyccemia augments ischemic brain damage: A neuropathological study in the rat. Neurology 1982;32: Nedegaard M. Transient focal ischemia in hyperglycemic rats is associated with increased cerebral infarction. Brain Res 1987;408: Li P-A, Siesjo BK. Role of hypergylcemia-related acidosis in ischemic brain damage. Acta Physiol Scand 1997;161: Kiers L, Davis SM, Larkins R, Hopper J, Tress B, Rossiter SC, et al. Stroke topography and outcome in relation to hyperglycemia and diabetes. J Neurol Neurosurg Psychiatry 1992;55: Candelise L, Landi G, Orazio EN, Boccardi E. Prognostic significance of hyperglycemia in acute stroke. Arch Neurol ; 4 2 : Matchar DB, Divine GW, Heyman A, Feussner JR. The influence of hyperglyccemia on outcome of cerebral infarction. Ann Intern Med 1992;117: Bruno A, Biller J, Adams HP Jr, Clarke WR, Woolson RF, Williams LS, et al. Acute blood glucose level and outcome from ischemic stroke. Trial of ORG in Acute Ischemic Stroke Treatment(TOAST) Investigators. Neurology 1999;52: Lundgren J, Smith M-L, Siesjo BK. Influence of moderate hypothermia on ischemic brain damage incurred under hyperglycemic conditions. Exp Brain Res 1991;84: Dietrich WD, Alonso O, Busto R. Moderate hyperglycemia worsens acute blood-brain barrier injury after forebrain ischemia in rats. Stroke 1993;24: Vannucci R, Rossini A, Towfighi J. Effect of hyperglycemia on ischemic brain damage during hypothermic circulatory arrest in newborn dogs. Pediatr Res 1996;40: Li P-A, He Q-P, Miyashita H, Howllet W, Siesjo BK, Shuaib A. Hypothermia ameliorates ischemic brain damage and suppresses the release of extracellular amino acids in both normo- and hyperglycemic subjects. Exp Neurol 1999;158: Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 1989;20: Welsh FA, Sims RE, Harris VA. Mild hypothermia prevents ischemic injury in gerbil hippocampus. J Cereb Blood Flow Metab 1990;10: Chopp M, Chen H, Dereski MO, Garcia JH. Mild hypothermic intervention after graded ischemic stress in rats. Stroke 1991;22: Siesjo BK, Katsura K, Kristian T. Acidosis-Related Damage. In: Siesjo BK, Wieloch T. Adv Neurol Vol. 71. Philadelphia: Lippincott-Raven, 1996; Yip P, He Y, Hsu C, Garg N, Marangos P, Hogan E. Effect of plasma glucose on infarct size in focal cerebral ischemia-reperfusion. N e u r o l o g y ; 4 1 : Li C, Li P-A, He Q-P, Ouyang Y-B, Siesjo BK. Effects of streptozotocin-induced hyperglycemia on brain damage following transient ischemia. Neurobiol Dis ; 5 : J Korean Neurol Assoc / Volume 18 / November,

Combination of Intraischemic and Postischemic Hypothermia Provides Potent and Persistent Neuroprotection Against Temporary Focal Ischemia in Rats

Combination of Intraischemic and Postischemic Hypothermia Provides Potent and Persistent Neuroprotection Against Temporary Focal Ischemia in Rats H. Yanamoto, MD, DMSc; I. Nagata, MD, DMSc; I. Nakahara,