Contribution of Bradykinin Receptors to the Development of Secondary Brain Damage After Experimental Subarachnoid Hemorrhage
Contribution of Bradykinin Receptors to the Development of Secondary Brain Damage After Experimental Subarachnoid Hemorrhage
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DOI：
10.1227/neu.0b013e31820a0024
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发表时间：
2011-04-01
期刊：
影响因子：
4.8
通讯作者：
Plesnila, Nikolaus
中科院分区：
文献类型：
--
作者：
Schoeller, Karsten;Feiler, Sergej;Plesnila, Nikolaus
背景：蛛网膜下腔出血(SAH)是病死率和发病率最高的卒中亚型。目的：探讨促炎性缓激肽B-1和B-2受体在蛛网膜下腔出血的病理生理机制中的作用。方法：采用血管内穿刺法建立SAH模型。持续监测SAH后60分钟的颅内压、局部脑血流量和平均动脉压。SAH后24小时测量脑含水量，连续7天每天评估死亡率、神经功能和体重。结果：两组间的颅内压、局部脑血流量和平均动脉压无差异。野生型小鼠死亡率为60%，B1R-/-小鼠死亡率为82%，而B2R-/-小鼠死亡率仅为20%(P<；0.05)。与野生型小鼠相比，B2R-/-小鼠表现出不那么严重的神经功能缺失(P<；0.05)，体重减轻(P<；0.05)，脑水肿形成明显减少(P<；0.05)。结论：缓激肽B-2受体介导的信号转导与SAH后小鼠的死亡率和继发性脑损伤有关。因此，B-2受体可能是治疗SAH的新靶点。
BACKGROUND: Subarachnoid hemorrhage (SAH) is the stroke subtype with the highest mortality and morbidity. Which molecular events mediate brain damage after SAH is not well understood.OBJECTIVE: To investigate the role of proinflammatory bradykinin B-1 and B-2 receptors for the pathophysiology of SAH.METHODS: B-1 and B-2 receptor knockout or wild-type mice were subjected to SAH by endovascular puncture. Intracranial pressure, regional cerebral blood flow, and mean arterial blood pressure were continuously monitored up to 60 minutes after SAH. Brain water content was quantified 24 hours after SAH; mortality, neurological function, and body weight were assessed daily for 7 days after hemorrhage.RESULTS: Intracranial pressure, regional cerebral blood flow, and mean arterial blood pressure did not differ between groups. Mortality was 60% in wild-type mice and 82% in B1R-/- mice but only 20% in B2R-/- animals (P < .05). B2R-/- mice also exhibited less severe neurological deficits (P < .05), a less pronounced loss of body weight (P < .05), and significantly less brain edema formation (P < .05) compared with wild-type mice.CONCLUSION: Signaling mediated by bradykinin B-2 receptors contributes to mortality and secondary brain damage after SAH in mice. Thus, B-2 receptors may represent novel targets for the treatment of SAH.