Intracerebral hirudin injection attenuates ischemic damage and neurologic deficits without altering local cerebral blood flow
Intracerebral hirudin injection attenuates ischemic damage and neurologic deficits without altering local cerebral blood flow
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DOI：
10.1097/01.wcb.0000100062.36077.84
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发表时间：
2004-02-01
影响因子：
6.3
通讯作者：
Xi, GH
中科院分区：
文献类型：
--
作者：
Karabiyikoglu, M;Hua, Y;Xi, GH
人们对使用凝血酶抑制剂来减少中风的发生或增强组织纤溶酶原激活物诱导的再灌注产生了相当大的兴趣。然而，越来越多的证据表明凝血酶也可能具有影响缺血性脑损伤的血管外效应。雄性Sprague-Dawley大鼠进行90分钟的暂时大脑中动脉（MCA）闭塞或假手术，以检查凝血酶和蛋白酶激活受体-1（PAR-1）的表达。在另一组大鼠中，将MCA闭塞90分钟，向尾状核注射10 U水蛭素或相同体积的溶剂，然后再灌注长达28天，以测试局部凝血酶抑制对缺血性损伤的影响，神经学结果和脑血流量（CBF）。凝血酶免疫反应性增加，在缺血尾状核在4和24小时，而PAR-1的表达是不变的。水蛭素在24小时减少了尾状核的梗死体积（79 ± 41 vs. 115 ± 20 mm（3），P < 0.05），并在28天导致尾状核更大的残留组织体积（17.6 ± 3.9 vs. 11.8 ± 6.3 mm（3），P < 0.05）。水蛭素治疗也有有益的影响体重和改善神经功能缺损测试前肢放置和前肢使用不对称在28天的生存。水蛭素的这些有益作用与再灌注期间局部CBF的改善无关。这些结果表明，除了对凝血和循环的影响，凝血酶抑制剂还具有直接的神经保护作用，可考虑用于卒中治疗。
There has been considerable interest in the use of thrombin inhibitors to reduce the occurrence of stroke or to potentiate tissue plasminogen activator-induced reperfusion. However, there is growing evidence that thrombin may also have extravascular effects that influence ischemic brain injury. Male Sprague-Dawley rats were subjected to either 90 minutes of temporary middle cerebral artery (MCA) occlusion or sham operation to examine thrombin and protease activated receptor-1 (PAR-1) expression. In another set of rats, the MCA was occluded for 90 minutes and 10 U of hirudin or the same volume of vehicle was injected into the caudate followed by reperfusion for up to 28 days, to test the effects of local thrombin inhibition on ischemic damage, neurologic outcome and cerebral blood flow (CBF). Thrombin immunoreactivity was increased in the ischemic caudate at 4 and 24 hours, whereas PAR-1 expression was unchanged. Hirudin reduced infarct volume in the caudate at 24 hours (79 +/- 41 vs. 115 +/- 20 mm(3), P < 0.05) and resulted in a larger residual tissue volume in the caudate at 28 days (17.6 +/- 3.9 vs. 11.8 +/- 6.3 mm(3), P < 0.05). Hirudin treatment also had a beneficial effect on body weight and ameliorated neurologic deficits tested by forelimb placing and forelimb use asymmetry during 28 days survival. These beneficial effects of hirudin were not associated with improved regional CBF during reperfusion. These results suggest that, in addition to their effects on coagulation and circulation, thrombin inhibitors also have direct neuroprotective properties and may be considered in stroke therapy.