Neuroprotection by Sildenafil: Neuronal Networks Potentiation in Acute Experimental Stroke
Neuroprotection by Sildenafil: Neuronal Networks Potentiation in Acute Experimental Stroke
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西地那非的神经保护：急性实验性脑卒中的神经元网络增强
DOI：
10.1111/cns.12162
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发表时间：
2014-01-01
影响因子：
5.5
通讯作者：
Yang, Jing-Yu
中科院分区：
文献类型：
--
作者：
Chen, Xue-Mei;Wang, Nan-Nan;Yang, Jing-Yu
目的西地那非是一种5型磷酸二酯酶抑制剂，通过增加cGMP水平和触发神经发生来促进缺血大鼠的功能恢复。本研究的目的是进一步探讨西地那非mechanism.MethodsMale Sprague-Dawley大鼠进行大脑中动脉闭塞和再灌注，然后通过腹膜内或静脉内治疗西地那非开始2 h后。于再灌注后第1天或第7天进行行为学检查，并于脑梗死后24 h进行脑梗死、脑水肿、尼氏染色、Fluoro-Jade B染色及电镜观察。cGMP依赖的Nogo-66受体（Nogo-R）通路，突触素，PSD-95/神经元型一氧化氮合酶（nNOS），脑源性神经营养因子（BDNF）/原肌球蛋白相关激酶B（Trk B），和神经生长因子（NGF）/原肌球蛋白相关激酶A（TrkA）进行了测量。此外，西地那非减少神经元的损失，并调节cGMP依赖性Nogo-R通路的表达。结论西地那非对急性脑卒中损伤的神经元有明显的保护作用，其保护作用是通过cGMP依赖的Nogo-R通路、NGF/TrkA和BDNF/TrkB介导的。
AimsSildenafil, a phosphodiesterase type 5 inhibitor, has been found to produce functional recovery in ischemic rats by increasing the cGMP level and triggering neurogenesis. The aim of this study was to investigate further sildenafil mechanisms.MethodsMale Sprague-Dawley rats underwent middle cerebral artery occlusion and reperfusion, followed by intraperitoneal or intravenous treatment of sildenafil starting 2h later. Behavioral tests were performed on day 1 or day 7 after reperfusion, while cerebral infarction, edema, Nissl staining, Fluoro-Jade B staining, and electron microscopy studies were carried out 24h poststroke. The cGMP-dependent Nogo-66 receptor (Nogo-R) pathway, synaptophysin, PSD-95/neuronal nitric oxide synthases (nNOS), brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB), and nerve growth factor (NGF)/tropomyosin-related kinase A (TrkA) were measured.ResultsSildenafil enhanced neurological recovery and inhibited infarction, even following delayed administration 4h after stroke onset. Furthermore, sildenafil reduced the loss of neurons and modulated the expressions of the cGMP-dependent Nogo-R pathway. Moreover, sildenafil protected the structure of synapses and mediated the expressions of synaptophysin, PSD-95/nNOS, BDNF/TrkB, and NGF/TrkA.ConclusionsSildenafil produces significant neuroprotective effects on injured neurons in acute stroke, and these are mediated by the cGMP-dependent Nogo-R pathway, NGF/TrkA, and BDNF/TrkB.