The effects of selective brain hypothermia on intracerebral hemorrhage in rats

The effects of selective brain hypothermia on intracerebral hemorrhage in rats
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DOI:
10.1016/j.expneurol.2007.08.018
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发表时间:
2007-12-01
影响因子:
5.3
通讯作者:
Colbourne, Frederick
Colbourne, Frederick
中科院分区:
医学2区
文献类型:
--
作者:
Fingas, Matthew;Clark, Darren L.;Colbourne, Frederick

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在动物模型和心脏骤停患者中,持续低温有效治疗全脑缺血性损伤。此外,基于令人鼓舞的动物研究结果,正在进行临床试验,以评估缺血性中风的疗效。脑出血(ICH)是一种更具破坏性的卒中,但其损伤机制与缺血相同。因此,ICH可能适合低温治疗。在这项研究中,我们测试了选择性脑低温是否能改善通过向纹状体注入100 μ L自体全血造成的大鼠脑出血后的结果。纹状体低温(类似于32摄氏度)是用一种新的方法(植入冷却线圈)诱导的,这种方法不会引起全身冷却,从而为中风提供了比全身低温更安全和更有效的治疗方法。脑出血后4天出现水肿,但在3天达到峰值(类似于5%)。此时,通过在ICH后1小时开始冷却(持续3天),其显著降低(接近2%)。接下来,我们确定1和12小时延迟冷却治疗(持续4天)是否会减轻功能障碍和病变大小。未经治疗的(非温热)ICH导致明显的前肢使用不对称,以及行走和熟练伸手的缺陷。这些缺陷不受低温的影响,在1个月时组织丢失的体积(类似于20 mm(3))也是如此。因此,减轻水肿不会导致行为或组织学获益。总之,虽然需要对替代冷却方案和ICH模型进行额外的研究,但这些研究结果表明,虽然低温可减轻水肿,但在ICH后不会直接具有神经保护作用。(c)2007年爱思唯尔公司All rights reserved.
Prolonged hypothermia effectively treats global cerebral ischemic injury in animal models as well as in cardiac arrest victims. Furthermore, clinical trials, based upon encouraging animal findings, are underway to assess efficacy in ischemic stroke. Intracerebral hemorrhage (ICH) is a more devastating stroke, but one that shares mechanisms of injury with ischemia. Accordingly, ICH may be amenable to hypothermia treatment. In this study we tested whether selective brain hypothermia improves outcome after an ICH in rats created by infusing 100 mu L of autologous whole blood into the striatum. Striatal hypothermia (similar to 32 degrees C) was induced with a novel method (implanted cooling coil) that does not cause systemic cooling, thereby providing a safer and potentially more effective treatment for stroke than systemic hypothermia. Edema occurred for 4 days after ICH, but it peaked at 3 days (similar to 5%). At this time it was significantly reduced (to similar to 2%) by cooling starting 1 h after ICH (3 day duration). Next, we determined whether 1 and 12 h delayed cooling treatments (4 day duration) would lessen functional impairment and lesion size. Untreated (nonnothermic) ICH resulted in significant forelimb use asymmetry, as well as deficits in walking and skilled reaching. These deficits were unaffected by hypothermia, as was the volume of tissue lost (similar to 20 mm(3)) at 1 month. Thus, attenuated edema did not result in behavioral or histological benefit. In conclusion, while additional research with alternative cooling protocols and ICH models are required, these findings suggest that while hypothermia lessens edema, it will not be directly neuroprotective after ICH. (c) 2007 Elsevier Inc. All rights reserved.