Protective effects of 2-(2-benzonfuranyl)-2-imidazoline combined with tissue plasminogen activator after embolic stroke in rats
Protective effects of 2-(2-benzonfuranyl)-2-imidazoline combined with tissue plasminogen activator after embolic stroke in rats
复制标题
2-(2-苯并呋喃基)-2-咪唑啉联合组织纤溶酶原激活剂对大鼠栓塞性脑卒中后的保护作用
DOI：
10.1016/j.brainres.2018.08.027
复制
发表时间：
2018-11-15
期刊：
影响因子：
2.9
通讯作者：
Han，Zhao
中科院分区：
文献类型：
--
作者：
Guo，Xiaoling;Zhang，Linlei;Han，Zhao
Stroke is the third leading cause of death and disability in developing countries. The effective therapy for acute ischemic stroke is thrombolysis with recombinant tissue plasminogen activator (rt-PA) within 4.5 h of stroke onset. An effective post-ischemic neuroprotectant would extend the advantages of rt-PA, and protect against complications of thrombolysis. We previously reported that 2-(2-benzofuranyl)-2-imidazoline (2-BFI), a newly discovered ligand for high-affinity type 2 imidazoline receptor (I2R), provides neuroprotection against ischemic stroke in rats. Here we investigated the protective effects of 2-BFI in combination with delayed intravenous rt-PA after stroke induced by embolic middle cerebral artery occlusion (eMCAO) in rats. Infarct size was determined using 2,3,5-triphenyltrazolium chloride staining, while neurological deficit was assessed based on neurological score. Numbers of apoptotic cellsin vivowere estimated using TUNEL stain, and expression of the pro-apoptotic protein BAX and anti-apoptotic protein BCL-2 were quantified by Western blotting. The results showed that 2-BFI (3 mg/kg) administered at 0.5 h after embolic MCAO combined with rt-PA (10 mg/kg) administered at 6 h reduced brain infarct size, mitigated neurological deficit, decreased the number of TUNEL-positive cells, down-regulated BAX expression, and up-regulated BCL-2 expression. These findings suggest that 2-BFI may extend the therapeutic window of rt-PA to 6 h after embolic stroke onset in rats.
