Acute treatment with candesartan reduces early injury after permanent middle cerebral artery occlusion.
Acute treatment with candesartan reduces early injury after permanent middle cerebral artery occlusion.
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DOI：
10.1007/s12975-010-0061-1
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发表时间：
2011-06-01
影响因子：
6.9
通讯作者：
Fagan SC
中科院分区：
文献类型：
--
作者：
Guan W;Kozak A;El-Remessy AB;Johnson MH;Pillai BA;Fagan SC
我们已经证明，再灌注开始后立即降低血压（BP）可减少神经血管损伤，改善实验性脑缺血后的功能结局，坎地沙坦在改善长期功能结局方面特别有效。在这项研究中，我们试图确定在存在脑动脉闭塞的情况下，坎地沙坦早期降低血压是否会减少损伤并改善实验性卒中后的结局。雄性Wistar大鼠大脑中动脉闭塞（MCAO）24小时或7天。在MCAO后3 h静脉内给予1 mg/kg坎地沙坦单次给药。动物在3 h、24 h和7天时接受神经行为测试，并通过遥测测量血压。收集动物的脑组织用于梗死面积（24小时和7天）、血红蛋白含量、基质金属蛋白酶（MMP）活性和血管内皮生长因子（VEGF）表达（仅24小时）。坎地沙坦在MCAO后24小时显著降低血压、梗死面积（−20%; p=0.021）、血红蛋白过量（−50%; p=0.0013）和水肿（−35%; p=0.0005）。与生理盐水相比，这导致缺血半球的脑灌注不足减少（p=0.034），并显著改善Bederson评分和爪抓力。MMP-2，MMP-9和VEGF显着增加MCAO，但坎地沙坦和生理盐水治疗的动物之间没有差异。第7天的行为结果无显著差异。坎地沙坦降低血压可减少实验性卒中后早期脑损伤，即使动脉仍然闭塞。然而，在再灌注动物中观察到的早期益处在7天时并不持续。坎地沙坦的神经保护和神经修复特性可能通过不同的机制发生。
We have shown that reduction of blood pressure (BP) immediately after the onset of reperfusion reduced neurovascular damage and improved functional outcome after experimental cerebral ischemia and candesartan is particularly effective in improving long-term functional outcome. In this study, we sought to determine if early BP lowering with candesartan, in the presence of an occluded cerebral artery, will reduce injury and improve outcome after experimental stroke. Male Wistar rats underwent 24 h or 7 days of middle cerebral artery occlusion (MCAO). A single dose of 1 mg/kg candesartan was administered intravenously at 3 h after MCAO. Animals received neurobehavioral testing at 3 h, 24 h, and 7 days, and blood pressure was measured by telemetry. Animals had brain tissue collected for infarct size (24 h and 7 days), hemoglobin content, matrix metalloproteinase (MMP) activity, and vascular endothelial growth factor (VEGF) expression (24 h only). Candesartan significantly decreased blood pressure, infarct size (−20%; p=0.021), hemoglobin excess (−50%; p=0.0013), and edema (−35%; p=0.0005) at 24 h after MCAO. This resulted in a reduced cerebral perfusion deficit (p=0.034) in the ischemic hemisphere compared with saline and significantly improved Bederson scores and paw grasp. MMP-2, MMP-9, and VEGF were significantly increased by MCAO, but there were no differences between candesartan- and saline-treated animals. There were no significant differences in behavioral outcome at day 7. BP lowering with candesartan reduces early brain injury after experimental stroke even when the artery remains occluded. The early benefits were not sustained at 7 days, as seen in reperfused animals, however. The neuroprotection and neurorestorative properties of candesartan may occur by separate distinct mechanisms.
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影响因子：
2.9
作者：
Sare, Gillian M.;Geeganage, Chamila;Bath, Philip M. W.
通讯作者：
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影响因子：
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作者：
BEDERSON, JB;PITTS, LH;BARTKOWSKI, H
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DOI：
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发表时间：
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影响因子：
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作者：
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DOI：
10.1124/jpet.109.157941
发表时间：
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影响因子：
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作者：
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通讯作者：
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作者：
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