Adjuvant treatment with neuroserpin increases the therapeutic window for tissue-type plasminogen activator administration in a rat model of embolic stroke
Adjuvant treatment with neuroserpin increases the therapeutic window for tissue-type plasminogen activator administration in a rat model of embolic stroke
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DOI：
10.1161/01.cir.0000023942.10849.41
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发表时间：
2002-08-06
期刊：
影响因子：
37.8
通讯作者：
Chopp, M
中科院分区：
文献类型：
--
作者：
Zhang, ZG;Zhang, L;Chopp, M
背景-卒中后，组织型纤溶酶原激活剂（tPA）在血管内的溶栓作用是有益的，而其在血管外对缺血神经元的作用是有害的。我们测试的假设，neuroserpin，一种天然的tPA抑制剂，减少tPA诱导的神经元毒性，并增加其治疗窗口栓塞stroke.Methods和Results-Rats进行栓塞大脑中动脉闭塞（MCAO）。用神经丝氨酸蛋白酶抑制剂与重组人tPA组合（n=7）、单独的tPA（n=7）或盐水（n=9）处理缺血脑。在缺血后3小时，脑池内注射神经丝氨酸蛋白酶抑制剂（20穆尔的16 μ mol/L活性神经丝氨酸蛋白酶抑制剂），4小时后静脉内给予tPA（10 mg/kg）。进行MRI测量以研究血脑屏障（BBB）渗漏和缺血性病变体积。缺血后4小时单独给予tPA显着（P
Background-After stroke, the thrombolytic effect of tissue-type plasminogen activator (tPA) in the intravascular space is beneficial, whereas its extravascular effect on ischemic neurons is deleterious. We tested the hypothesis that neuroserpin, a natural inhibitor of tPA, reduces tPA-induced neuronal toxicity and increases its therapeutic window for treatment of embolic stroke.Methods and Results-Rats were subjected to embolic middle cerebral artery occlusion (MCAO). Ischemic brains were treated with neuroserpin in combination with recombinant human tPA (n=7), tPA alone (n=7), or saline (n=9). Neuroserpin (20 muL of 16 mumol/L active neuroserpin) was intracisternally injected 3 hours and tPA (10 mg/kg) was intravenously administered 4 hours after ischemia. MRI measurements were performed to study blood brain barrier (BBB) leakage and ischemic lesion volume. Administration of tPA alone 4 hours after ischemia significantly (P