Neuroprotection by Sildenafil: Neuronal Networks Potentiation in Acute Experimental Stroke

作者：Chen, Xue-Mei; Wang, Nan-Nan; Zhang, Tian-Yu; Wang, Fang; Wu, Chun-Fu; Yang, Jing-Yu^*

来源：CNS Neuroscience & Therapeutics, 2014, 20(1): 40-49.

DOI：10.1111/cns.12162

• Neuronal network
• Neuroprotection
• Sildenafil
• Stroke

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.

• 出版日期2014-1
• 单位沈阳药科大学