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CNS Neurosci Ther. 2014 Jan;20(1):40-9. doi: 10.1111/cns.12162. Epub 2013 Aug 30.

Neuroprotection by sildenafil: neuronal networks potentiation in acute experimental stroke.

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1
Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, China.

Abstract

AIMS:

Sildenafil, 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.

METHODS:

Male Sprague-Dawley 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, Nissl staining, Fluoro-Jade B staining, and electron microscopy studies were carried out 24 h 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.

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 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.

CONCLUSIONS:

Sildenafil 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.

KEYWORDS:

Neuronal network; Neuroprotection; Sildenafil; Stroke

PMID:
24034153
DOI:
10.1111/cns.12162
[Indexed for MEDLINE]

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