Open AccessN europrotection by S ildenafil: N euronal N etworks P otentiation in A cute E xperimental S troke
Author(s) -
Chen XueMei,
Wang NanNan,
Zhang TianYu,
Wang Fang,
Wu ChunFu,
Yang JingYu
Publication year - 2014
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12162
Subject(s) - sildenafil , tropomyosin receptor kinase b , neuroprotection , nerve growth factor , synaptophysin , tropomyosin receptor kinase a , medicine , brain derived neurotrophic factor , neurotrophic factors , neurotrophin , anesthesia , pharmacology , nissl body , endocrinology , neuroscience , biology , receptor , pathology , immunohistochemistry , staining
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 .