Delayed Treatment with Sildenafil Enhances Neurogenesis and Improves Functional Recovery in Aged Rats After Focal Cerebral Ischemia.
From: Department of Neurology, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA.
Journal of neuroscience research
- Publish Date: May 2006
- ISSN: 0360-4012
- Volume: 83
- Issue: 7
- Pages: 1213-9
- Medium: Print
- Language: English
- Citation (JAMA): Zhang Rui Lan, Zhang Zhenggang, Zhang Li, et al. Delayed Treatment with Sildenafil Enhances Neurogenesis and Improves Functional Recovery in Aged Rats After Focal Cerebral Ischemia.. J. Neurosci. Res. May 2006;83:1213-9
Abstract
Increasing age decreases the number of new neurons in the dentate gyrus and the subventricular zone (SVZ). Sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, enhances neurogenesis in young rats. The present study tested the hypothesis that sildenafil augments neurogenesis in aged rats after focal cerebral ischemia. Nonischemic aged (18 months, n = 6) Wistar rats exhibited a significant reduction of actively proliferating and relatively quiescent cells in the SVZ measured by the number of minichromosome maintenance protein-2-positive (MCM-2+) cells, a marker of the proliferating cells, compared with nonischemic young (3-4 months, n = 8) rats. Occlusion of the middle cerebral artery did not increase the number of MCM-2+ cells in the SVZ of aged rats at 3 months after focal ischemia. However, treatment with sildenafil at a dose of 3 mg/kg (n = 8) daily for 7 consecutive days starting 7 days after focal ischemia significantly increased the number of MCM-2+ cells in the SVZ of aged rats compared with aged rats treated with saline (n = 8). Double immunostaining revealed that substantially more Ki67+ cells (a marker of proliferating cells) were doublecortin+ (a marker of migrating neuroblasts) in sildenafil-treated than in saline-treated aged animals. In addition, treatment with sildenafil significantly improved functional recovery compared with saline-treated rats. These data suggest that inhibition of PDE5 activity by sildenafil augments neurogenesis in the SVZ of aged ischemic rats, although these rats have reduced numbers of neural progenitor and stem cells in the SVZ.
Mesh Headings (Keywords): 3’,5’-Cyclic-GMP Phosphodiesterases, Aging, Animals, Brain Ischemia, Cell Division, Cell Proliferation, Cerebral Cortex, Cyclic Nucleotide Phosphodiesterases, Type 5, Disease Models, Animal, Ki-67 Antigen, MCM1 Protein, Male, Microtubule-Associated Proteins, Neuronal Plasticity, Neuropeptides, Phosphodiesterase Inhibitors, Piperazines, Purines, Rats, Rats, Wistar, Recovery of Function, Stem Cells, Sulfones, Up-Regulation
Check for Full Text / PubMed Unique Identifier (PMID): 16511865
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.