N europrotection by S ildenafil: N euronal N etworks P otentiation in A cute E xperimental S troke

Summary Aims Sildenafil, a phosphodiesterase type 5 inhibitor, has been found to produce functional recovery in ischemic rats by increasing the c GMP level and triggering neurogenesis. The aim of this study was to investigate further sildenafil mechanisms. Methods Male S prague‐ D awley rats underwent middle cerebral artery occlusion and reperfusion, followed by intraperitoneal or intravenous treatment of sildenafil starting 2 h later. Behavioral tests were performed on day 1 or day 7 after reperfusion, while cerebral infarction, edema, N issl staining, F luoro‐ J ade B staining, and electron microscopy studies were carried out 24 h poststroke. The c GMP ‐dependent N ogo‐66 receptor ( N ogo‐ R ) pathway, synaptophysin, PSD ‐95/neuronal nitric oxide synthases (n NOS ), brain‐derived neurotrophic factor ( BDNF )/tropomyosin‐related kinase B ( T rk B ), and nerve growth factor ( NGF )/tropomyosin‐related kinase A ( T rk A ) were measured. Results Sildenafil enhanced neurological recovery and inhibited infarction, even following delayed administration 4 h after stroke onset. Furthermore, sildenafil reduced the loss of neurons and modulated the expressions of the c GMP ‐dependent N ogo‐ R pathway. Moreover, sildenafil protected the structure of synapses and mediated the expressions of synaptophysin, PSD ‐95/n NOS , BDNF / T rk B , and NGF / T rk A . Conclusions Sildenafil produces significant neuroprotective effects on injured neurons in acute stroke, and these are mediated by the c GMP ‐dependent N ogo‐ R pathway, NGF / T rk A , and BDNF / T rk B .