Modifying neurorepair and neuroregenerative factors with tPA and edaravone after transient middle cerebral artery occlusion in rat brain
Modifying neurorepair and neuroregenerative factors with tPA and edaravone after transient middle cerebral artery occlusion in rat brain
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DOI：
10.1016/j.brainres.2011.12.016
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发表时间：
2012-02-03
期刊：
影响因子：
2.9
通讯作者：
Abe, Koji
中科院分区：
文献类型：
--
作者：
Deguchi, Kentaro;Miyazaki, Kazunori;Abe, Koji
短暂性脑缺血后，神经修复和神经再生因子的表达变化与组织纤溶酶原激活剂（tPA）和自由基清除剂依达拉奉的影响进行了检查。在大鼠短暂性大脑中动脉闭塞（tMCAO）90 min期间，两次注射生理盐水或依达拉奉，然后在再灌注时注射相同的生理盐水或tPA。在tMCAO后4d检测梗死面积和与神经修复和神经再生相关的蛋白因子。检查的蛋白质因子是：硫酸软骨素蛋白聚糖神经聚糖，脑信号蛋白3A型（Sema 3A），髓鞘相关糖蛋白受体（Nogo受体，Nogo-R），突触再生因子（生长相关蛋白-43，GAP 43）和趋化因子netrin受体（在结直肠癌中缺失，DCC）。仅用依达拉奉或依达拉奉加tPA治疗的两个组与仅用溶媒或溶媒加tPA治疗的两个组相比显示梗死体积减少。免疫组织化学和蛋白质印迹分析表明，tPA降低了neurocan、Sema 3A、Nogo-R、GAP 43和DCC的蛋白表达，但依达拉奉恢复了这些蛋白表达。添加依达拉奉可阻止tPA诱导的这五种蛋白的减少。本研究首次证明，外源性tPA减少了参与抑制和促进轴突生长的蛋白因子，但依达拉奉改善了急性缺血后脑修复中的此类损伤。(C)2011爱思唯尔有限公司版权所有。
Changes in expression of neurorepair and neuroregenerative factors were examined after transient cerebral ischemia in relation to the effects of tissue plasminogen activator (tPA) and the free radical scavenger edaravone. Physiological saline or edaravone was injected twice during 90 min of transient middle cerebral artery occlusion (tMCAO) in rats, followed by the same saline or tPA at reperfusion. Sizes of the infarct and protein factors relating to neurorepair and neuroregeneration were examined at 4 d after tMCAO. The protein factors examined were: a chondroitin sulfate proteoglycan neurocan, semaphorin type 3A (Sema3A), a myelin-associated glycoprotein receptor (Nogo receptor, Nogo-R), a synaptic regenerative factor (growth associated protein-43, GAP43), and a chemotropic factor netrin receptor (deleted in colorectal cancer, DCC). Two groups treated by edaravone only or edaravone plus tPA showed a reduction in infarct volume compared to the two groups treated by vehicle only or vehicle plus tPA. Immunohistochemistry and western blot analyses indicated that protein expression of neurocan, Sema3A, Nogo-R, GAP43, and DCC was decreased with tPA, but recovered with edaravone. Additive edaravone prevented the reductions of these five proteins induced by tPA. The present study demonstrates for the first time that exogenous tPA reduced protein factors involved in inhibiting and promoting axonal growth, but that edaravone ameliorated such damage in brain repair after acute ischemia. (C) 2011 Elsevier B.V. All rights reserved.