Delayed treatment with sildenafil enhances neurogenesis and improves functional recovery in aged rats after focal cerebral ischemia
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. © 2006 Wiley‐Liss, Inc.
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Enhanced plasticity and neurological recovery after stroke were evident in both young and older animals.
“Enhanced plasticity and neurological recovery after stroke were evident not only in young but also in older animals.17,26,33”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [33]
Neurogenesis is stimulated in response to stroke and is substantially amplified by therapeutic interventions that promote functional recovery.
“Neurogenesis is stimulated in response to stroke and is substantially amplified by therapeutic interventions that promote functional recovery.33–36”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [33]
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References 37 · Cited by 138
- Authors
- Zhang, R. L., Zhang, Z., Zhang, L., Wang, Y., Zhang, C., & Chopp, M.
- Affiliations
- Henry Ford Health (US)
- Corresponding author
- Chopp, Michael
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2006-03
- Volume
- 83
- Issue
- 7
- Pages
- 1213-1219
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W1995792973
- Cited by
- 138
- References
- 37
- Citations by year
- 2024: 5 · 2023: 1 · 2022: 5 · 2021: 2 · 2020: 4 · 2019: 7 · 2018: 2 · 2017: 12 · 2016: 6 · 2015: 3 · 2014: 6 · 2013: 8 · 2012: 15
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01 HL 6476)
- National Institute of Neurological Disorders and Stroke (P01NS23393, P01NS023393, P01NS42345, R01 NS 38292, P01NS042345, R01NS038292)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- sildenafil, phosphodiesterase-5 inhibition, neurogenesis, subventricular zone, focal cerebral ischemia, aging, middle cerebral artery occlusion, MCM2, Ki-67, doublecortin, neural progenitor cells, functional recovery
- MeSH terms
- Sildenafil Citrate, Doublecortin Domain Proteins, Doublecortin Protein, Aging, Animals, Cell Division, Cerebral Cortex, Brain Ischemia, Disease Models, Animal, Male, Microtubule-Associated Proteins, Neuronal Plasticity, Neuropeptides, Phosphodiesterase Inhibitors, Piperazines, Purines, Stem Cells, Sulfones, 3',5'-Cyclic-GMP Phosphodiesterases, Up-Regulation, Rats, Wistar, Ki-67 Antigen, Recovery of Function, Minichromosome Maintenance 1 Protein, Cell Proliferation, Rats, Cyclic Nucleotide Phosphodiesterases, Type 5
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