ACTIVE THROMBOSIS, THROMBOLYSIS, AND STROKE OUTCOME

描述：虽然使用纤溶酶原激活剂溶栓是一种被接受的方法 中风的急性临床治疗仍需要充分评估，在 相关的动物模型，由此产生的再灌流的后果 代谢受损的脑组织。一种可逆性血栓性卒中模型 已经开发出，其中Ictus是通过光化学介导法启动的 (光栓性)阻塞大鼠大脑中动脉，导致 常规(rt-PA)溶栓耐药的无纤维蛋白血小板血栓 治疗。这种血栓可能是血管再通失败的主要原因。 临床上看起来。再灌流然后通过专有的光物理实现 促进血栓解除的过程，明显是通过增强穿透 抗血栓血浆因子。对于闭塞时间小于2小时的患者，大脑皮质 血流(CBF)在5-30分钟内建立，但稍后恢复全流量 可能需要使用凝血酶抑制剂(或纤溶酶原激活剂)来 清除瘀血引起的远端继发性血栓。尽管组织恢复是 预计与早期血流恢复重合，即“再灌流损伤” 伴随着不可逆的细胞变化，可能预示着梗塞的发生 在以后的时间，即使微循环被抗凝血酶保护 通过抑制P-选择素的表达进行治疗 白细胞停滞。发展为再灌注损伤的指标，如 P-选择素在内皮细胞和凝血酶激活的血小板上的表达 髓过氧化物酶活性和脂质过氧化副产物丙二醛和 4-羟基-2-壬烯醛将通过免疫染色程序进行监测 至1天。再灌注对内皮型一氧化氮合酶的影响 蛋白质和基因的表达将通过免疫染色和原位评估 杂交。3天后的结果，由组织学评估监测 正常和不完全性脑梗死区与时间相关 再灌注诱导治疗的过程及相关的分子变化。

DESCRIPTION: Although thrombolysis by plasminogen activators is an accepted acute clinical treatment for stroke there is still a need to evaluate fully, in a relevant animal model, the consequences of the resultant reperfusion for metabolically compromised brain tissue. A reversible model of thrombotic stroke has been developed, in which the ictus is initiated by photochemically mediated (photothrombotic) occlusion of the rat middle cerebral artery, resulting in a fibrin-free platelet thrombus resistant to conventional (rt-PA) thrombolytic treatment. Such thrombi may account for the majority of recanalization failures seen clinically. Reperfusion is then achieve photophysically by a proprietary process that facilitates dethrombosis, evidently by enhanced penetration of antithrombotic plasma factors. For occlusion times less than 2 hr, cortical cerebral blood flow (CBF) is established within 5-30 min, but full flow restoration at later times will likely require thrombin inhibitor (or plasminogen activator) administration to clear stasis-induced distal secondary thrombi. Although tissue recovery is expected to coincide with flow recovery at early times, "reperfusion injury" concomitant with irreversible cellular changes presaging infarction may occur at later times, even if the microcirculation is preserved by antithrombin treatment via inhibition of the expression of P-selectin, which precedes leukocyte stasis. Indicators of developing reperfusion injury such as expression of P-selectin on endothelium and on thrombin-activated platelets, myeloperoxidase activity, and lipid peroxidation byproducts malondialdehyde and 4-hydroxy-2-nonenal will be monitored by immunostaining procedures at times up to 1 day. The effect of reperfusion on endothelial nitric oxide synthase protein and gene expression will be assessed by immunostaining and in situ hybridization. Outcome at 3 days, monitored by histological evaluation of regions of frank and incomplete infarction, will be correlated with the time course of reperfusion-inducing treatments and associated molecular changes.