Glibenclamide Is Superior to Decompressive Craniectomy in a Rat Model of Malignant Stroke

被引:111
作者
Simard, J. Marc [1 ,2 ,3 ]
Tsymbalyuk, Natalia [1 ]
Tsymbalyuk, Orest [1 ]
Ivanova, Svetlana [1 ]
Yurovsky, Vladimir [1 ]
Gerzanich, Volodymyr [1 ]
机构
[1] Univ Maryland, Sch Med, Dept Neurosurg, Baltimore, MD 21201 USA
[2] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA
[3] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA
关键词
cerebral ischemia; malignant cerebral edema; white matter; glibenclamide; decompressive craniectomy; sulfonylurea receptor 1-regulated NC(Ca-ATP) channels; CEREBRAL-ARTERY INFARCTION; ISCHEMIC-STROKE; REPERFUSION; OCCLUSION; EDEMA; MORTALITY; RECEPTOR; CLONING; INJURY;
D O I
10.1161/STROKEAHA.109.572644
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and Purpose-Treating patients with malignant cerebral infarctions remains a major unsolved problem in medicine. Decompressive craniectomy (DC) improves the bleak outlook but is suboptimal. Using a rat model of severe ischemia/reperfusion with very high mortality due to malignant cerebral edema, we tested the hypothesis that blocking of sulfonylurea receptor 1-regulated NC(Ca-ATP) channels with glibenclamide would compare favorably to DC when reperfusion and treatment were begun 6 hours after onset of ischemia. Methods-Male Wistar rats underwent filament occlusion of the middle cerebral artery to reduce laser Doppler flowmetry perfusion signals by > 75%, with filament removal plus treatment 6 hours later. In rats treated with vehicle versus glibenclamide (10 mu g/kg IP plus 200 ng/h SC), we compared mortality, neurologic function, and brain swelling at 24 hours. In rats treated with DC versus glibenclamide, we compared neurologic function for 2 weeks and histologic outcomes. Results-Compared with vehicle, glibenclamide treatment reduced 24-hour mortality from 67% to 5% and reduced hemispheric swelling at 24 hours from 21% to 8%. DC eliminated 24-hour mortality, but neurologic function during the next 2 weeks was significantly better with glibenclamide compared with DC. Watershed cortex and deep white matter were significantly better preserved with glibenclamide compared with DC. Conclusions-In a rat model of severe ischemia/reperfusion, with reperfusion and treatment beginning 6 hours after onset of ischemia, glibenclamide is as effective as DC in preventing death from malignant cerebral edema but is superior to DC in preserving neurologic function and the integrity of watershed cortex and deep white matter. (Stroke. 2010;41:531-537.)
引用
收藏
页码:531 / 537
页数:7
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