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Cited by 384Neurogenesis and neuroplasticity mechanismsNeuroprotection in Cerebral IschemiaStroke Rehabilitation and Recovery

The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.

Sildenafil (Viagra) Induces Neurogenesis and Promotes Functional Recovery After Stroke in Rats

Zhang, Ruilan, Wang, Ying, Zhang, Li, Zhang, Zhenggang, Tsang, Wayne, Lu, Mei, Zhang, Lijie, Chopp, Michael·2002·Stroke
DOI 10.1161/01.str.0000034399.95249.59
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Abstract

Background and Purpose— We tested the hypothesis that sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, promotes functional recovery and neurogenesis after stroke. Methods— Male Wistar rats were subjected to embolic middle cerebral artery occlusion. Sildenafil (Viagra) was administered orally for 7 consecutive days starting 2 or 24 hours after stroke onset at doses of 2 or 5 mg/kg per day. Ischemic rats administered the same volume of tap water were used as a control group. Functional outcome tests (foot-fault, adhesive removal) were performed. Rats were killed 28 days after stroke for analysis of infarct volume and newly generated cells within the subventricular zone and the dentate gyrus. Brain cGMP levels, expression of PDE5, and localized cerebral blood flow were measured in additional rats. Results— Treatment with sildenafil significantly ( P <0.05) enhanced neurological recovery in all tests performed. There was no significant difference of infarct volume among the experimental groups. Treatment with sildenafil significantly ( P <0.05) increased numbers of bromodeoxyuridine-immunoreactive cells in the subventricular zone and the dentate gyrus and numbers of immature neurons, as indicated by βIII-tubulin (TuJ1) immunoreactivity in the ipsilateral subventricular zone and striatum. The cortical levels of cGMP significantly increased after administration of sildenafil, and PDE5 mRNA was present in both nonischemic and ischemic brain. Conclusions— Sildenafil increases brain levels of cGMP, evokes neurogenesis, and reduces neurological deficits when given to rats 2 or 24 hours after stroke. These data suggest that this drug that is presently in the clinic for sexual dysfunction may have a role in promoting recovery from stroke.

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Crossref · 10.1161/01.str.0000034399.95249.59

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  1. 10.1161/str.32.12.2926 · DOI
  2. 10.1161/str.27.11.2136 · DOI
  3. 10.1161/res.70.2.1310445 · DOI

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Metadata

Authors
Zhang, R., Wang, Y., Zhang, L., Zhang, Z., Tsang, W., Lu, M., Zhang, L., & Chopp, M.
Affiliations
  • Henry Ford Health (US)
  • From the Department of Neurology, Henry Ford Health Sciences Center, Detroit, Mich (R.Z., Y.W., L.Z., Z.Z., W.T., M.L., L.Z., M.C.), and Department of Physics, Oakland University, Rochester, Mich (M.C.).
ORCID
Venue
Stroke
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2002-11
Volume
33
Issue
11
Pages
2675-2680
ISSN
  • 0039-2499 (ISSN-L)
  • 1524-4628
DOI
10.1161/01.str.0000034399.95249.59
OpenAlex
W2105711200
Cited by
383
References
36
Citations by year
2026: 4 · 2025: 7 · 2024: 10 · 2023: 8 · 2022: 6 · 2021: 6 · 2020: 12 · 2019: 17 · 2018: 10 · 2017: 13 · 2016: 13 · 2015: 17 · 2014: 26 · 2013: 25 · 2012: 31
FWCI
3.26
Type
journal article
Language
en
Open access
closed
Locations
  • Stroke (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ns033627-08)
  • National Heart, Lung, and Blood Institute (R01HL064766, R01HL64766)
  • National Institute of Neurological Disorders and Stroke (P01NS23393, R01NS-33627, P01NS023393)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Neurology › Neuroprotection in Cerebral Ischemia
  • Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
Keywords
sildenafil, phosphodiesterase-5 inhibitors, neurogenesis, functional recovery, middle cerebral artery occlusion, cyclic GMP, subventricular zone, dentate gyrus, infarct size, cerebral blood flow, TUBB3, immature neurons
MeSH terms
Sildenafil Citrate, Animals, Behavior, Animal, Brain, Bromodeoxyuridine, Cell Count, Cell Division, Cerebrovascular Circulation, Corpus Striatum, Disease Models, Animal, Cyclic GMP, Male, Nerve Regeneration, Neurons, Phosphodiesterase Inhibitors, Piperazines, Purines, RNA, Messenger, Sulfones, 3',5'-Cyclic-GMP Phosphodiesterases, Treatment Outcome, Rats, Wistar, Dentate Gyrus, Recovery of Function, Stroke, Lateral Ventricles, Rats, Cyclic Nucleotide Phosphodiesterases, Type 5

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