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

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1161/01.str.0000034399.95249.59

Cites

36 of 36 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus
van Praag, H., Kempermann, G., & Gage, F. H. (1999) · Nature Neuroscience · doi:10.1038/6368 · Cited by 3,880
Running enhances neurogenesis, learning, and long-term potentiation in mice
van Praag, H., Christie, B. R., Sejnowski, T. J., & Gage, F. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.23.13427 · Cited by 2,904
Neurogenesis in the adult is involved in the formation of trace memories
Shors, T. J., Miesegaes, G. R., Beylin, A. V., Zhao, M., Rydel, T. A., & Gould, E. (2001) · Nature · doi:10.1038/35066584 · Cited by 2,014
Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms
Beavo, J. A. (1995) · Physiological Reviews · doi:10.1152/physrev.1995.75.4.725 · Cited by 1,788
Nitric Oxide Signaling in the Central Nervous System
Garthwaite, J., & Boulton, C. L. (1995) · Annual Review of Physiology · doi:10.1146/annurev.ph.57.030195.003343 · Cited by 1,664
Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia
Zhang, R. L., Zhang, Z. G., Zhang, L., & Chopp, M. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00117-8 · Cited by 576
Self-citation
Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain
Benraiss, A., Chmielnicki, E., Lerner, K., Roh, D., & Goldman, S. A. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-17-06718.2001 · Cited by 540
Cyclic GMP Phosphodiesterase-5: Target of Sildenafil
Corbin, J. D., & Francis, S. H. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.20.13729 · Cited by 536
Neurogenesis in Adult Mammals: Some Progress and Problems
Gould, E., & Gross, C. G. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-03-00619.2002 · Cited by 511
Signal transduction underlying growth cone guidance by diffusible factors
Song, H., & Poo, M. (1999) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(99)80052-x · Cited by 454

Show all 36 references

Research works printed but not linked: 3

10.1161/str.32.12.2926 · DOI
10.1161/str.27.11.2136 · DOI
10.1161/res.70.2.1310445 · DOI

Sorted by citations

Items 101–200 of 384

Dose-dependent neurorestorative effects of delayed treatment of traumatic brain injury with recombinant human erythropoietin in rats
Meng, Y., Xiong, Y., Mahmood, A., Zhang, Y., Qu, C., & Chopp, M. (2011) · Journal of neurosurgery · doi:10.3171/2011.3.jns101721 · Cited by 66
Self-citation
Emerging new uses of phosphodiesterase-5 inhibitors in cardiovascular diseases.
Kukreja, R. C., Salloum, F. N., Das, A., Koka, S., Ockaili, R. A., & Xi, L. (2011) · PubMed Central · Cited by 63
Regulation of Hippocampal cGMP Levels as a Candidate to Treat Cognitive Deficits in Huntington’s Disease
Saavedra, A., Giralt, A., Arumí, H., Alberch, J., & Pérez‐Navarro, E. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073664 · Cited by 63
Phosphodiesterase 5 inhibition at disease onset prevents experimental autoimmune encephalomyelitis progression through immunoregulatory and neuroprotective actions
Pifarré, P., Gutièrrez‐Mecinas, M., Prado, J., Usero, L., Roura‐Mir, C., Giralt, M., Hidalgo, J., & Garcı́a, A. (2013) · Experimental Neurology · doi:10.1016/j.expneurol.2013.10.021 · Cited by 62
Activated Protein C is Neuroprotective and Mediates New Blood Vessel Formation and Neurogenesis After Controlled Cortical Impact
Petraglia, A. L., Marky, A. H., Walker, C. T., Thiyagarajan, M., & Zloković, B. V. (2009) · Neurosurgery · doi:10.1227/01.neu.0000363148.49779.68 · Cited by 62
Phosphodiesterase 5 inhibition as a therapeutic target for ischemic stroke: A systematic review of preclinical studies
Ölmestig, J. N. E., Marlet, I. R., Hainsworth, A. H., & Kruuse, C. R. (2017) · Cellular Signalling · doi:10.1016/j.cellsig.2017.06.015 · Cited by 61
Cerebrolysin improves cognitive performance in rats after mild traumatic brain injury
Zhang, Y., Chopp, M., Meng, Y., Zhang, Z. G., Doppler, E., Winter, S., Schallert, T. J., Mahmood, A., & Xiong, Y. (2015) · Journal of neurosurgery · doi:10.3171/2014.11.jns14271 · Cited by 60
Self-citation
Improvement of neurological recovery and stimulation of neural progenitor cell proliferation by intrathecal administration of Sonic hedgehog
Bambakidis, N. C., Petrullis, M., Xu, K., Rothstein, B. D., Karampelas, I. H., Kuang, Y., Selman, W. R., LaManna, J. C., & Miller, R. H. (2012) · Journal of neurosurgery · doi:10.3171/2012.1.jns111285 · Cited by 60
Sildenafil Improves Dynamic Vascular Function in the Brain: Studies in Patients with Pulmonary Hypertension
Rosengarten, B., SCHERMULY, R. T., Voswinckel, R., Kohstall, M. G., Olschewski, H., Weißmann, N., Seeger, W., Kaps, M., Grimminger, F., & Ghofrani, H. A. (2005) · Cerebrovascular Diseases · doi:10.1159/000090555 · Cited by 60
Histological and functional outcomes after traumatic brain injury in mice null for the erythropoietin receptor in the central nervous system
Xiong, Y., Mahmood, A., Lu, D., Qu, C., Kazmi, H., Goussev, A. V., Zhang, Z. G., Noguchi, C. T., Schallert, T. J., & Chopp, M. (2008) · Brain Research · doi:10.1016/j.brainres.2008.06.127 · Cited by 58
Self-citation
Therapeutic Potential of Phosphodiesterase Inhibitors against Neurodegeneration: The Perspective of the Medicinal Chemist
Ribaudo, G., Ongaro, A., Zagotto, G., Memo, M., & Gianoncelli, A. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00244 · Cited by 58
Neurogenesis and Apoptotic Cell Death
Moskowitz, M. A., & Lo, E. H. (2003) · Stroke · doi:10.1161/01.str.0000054047.14853.ad · Cited by 57
Effects of daily low-dose treatment with phosphodiesterase type 5 inhibitor on cognition, depression, somatization and erectile function in patients with erectile dysfunction: a double-blind, placebo-controlled study
Shim, Y. S., Pae, C.-U., Cho, K. J., Kim, S. W., Kim, J. C., & Koh, J. S. (2013) · International Journal of Impotence Research · doi:10.1038/ijir.2013.38 · Cited by 53
Use of Phosphodiesterase Type 5 Inhibitors May Adversely Impact Biochemical Recurrence after Radical Prostatectomy
Michl, U. H. G., Molfenter, F., Graefen, M., Tennstedt, P., Ahyai, S., Beyer, B., Budäus, L., Haese, A., Hans Heinzer, A., Oh, S. J., et al. (2014) · The Journal of Urology · doi:10.1016/j.juro.2014.08.111 · Cited by 52
Rodent Models of Vascular Cognitive Impairment
Tuo, Q., Zou, J.-J., & Lei, P. (2020) · Journal of Molecular Neuroscience · doi:10.1007/s12031-020-01733-2 · Cited by 56
Rehabilitation of erectile function following radical prostatectomy
McCullough, A. (2008) · Asian Journal of Andrology · doi:10.1111/j.1745-7262.2008.00366.x · Cited by 52
Transplantation of Human Urine-Derived Stem Cells Transfected with Pigment Epithelium-Derived Factor to Protect Erectile Function in a Rat Model of Cavernous Nerve Injury
Yang, Q., Chen, X., Zheng, T., Han, D., Zhang, H., Shi, Y., Bian, J., Sun, X., Xia, K., Liang, X., et al. (2016) · Cell Transplantation · doi:10.3727/096368916x691448 · Cited by 51
Real-time monitoring of phosphodiesterase inhibition in intact cells
Herget, S., Lohse, M. J., & Nikolaev, V. O. (2008) · Cellular Signalling · doi:10.1016/j.cellsig.2008.03.011 · Cited by 50
Safety of Sildenafil in Infants*
Samiee‐Zafarghandy, S., Smith, P. B., & van den Anker, J. N. (2014) · Pediatric Critical Care Medicine · doi:10.1097/pcc.0000000000000077 · Cited by 49
Effects of the PDE5-inhibitor vardenafil in a mouse stroke model
Royl, G., Balkaya, M., Lehmann, S., Lehnardt, S., Stohlmann, K., Lindauer, U., Endres, M., Dirnagl, U., & Meisel, A. (2009) · Brain Research · doi:10.1016/j.brainres.2009.01.061 · Cited by 49
Phosphodiesterase 5 Inhibition Attenuates Cerebral Vasospasm and Improves Functional Recovery After Experimental Subarachnoid Hemorrhage
Han, B. H., Vellimana, A. K., Zhou, M., Milner, E., & Zipfel, G. J. (2011) · Neurosurgery · doi:10.1227/neu.0b013e31822ec2b0 · Cited by 49
Sildenafil Reduces Insulin-Resistance in Human Endothelial Cells
Mammi, C., Pastore, D., Lombardo, M. F., Ferrelli, F., Caprio, M., Consoli, C., Tesauro, M., Gatta, L., Fini, M., Federici, M., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014542 · Cited by 49
Sildenafil Treatment of Subacute Ischemic Stroke: A Safety Study at 25-mg Daily for 2 Weeks
Silver, B., McCarthy, S., Lü, M., Mitsias, P. D., Russman, A., Katramados, A. M., Morris, D. C., Lewandowski, C., & Chopp, M. (2009) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2009.01.007 · Cited by 47
Self-citation
Phosphodiesterase 5 inhibitors prevent 3,4‐methylenedioxymethamphetamine‐induced 5‐HT deficits in the rat
Puerta, E., Hervías, I., Goñi‐Allo, B., Lasheras, B., Jordán, J., & Aguirre, N. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05825.x · Cited by 46
Sildenafil: efficacy, safety, tolerability and mechanism of action in treating erectile dysfunction
Francis, S. H., & Corbin, J. D. (2005) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.1.2.283 · Cited by 46
Impact of inhibition of erythropoietin treatment-mediated neurogenesis in the dentate gyrus of the hippocampus on restoration of spatial learning after traumatic brain injury
Zhang, Y., Chopp, M., Mahmood, A., Meng, Y., Qu, C., & Xiong, Y. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.02.015 · Cited by 47
Self-citation
Phosphodiesterase 5A Inhibitors Improve Functional Recovery after Stroke in Rats: Optimized Dosing Regimen with Implications for Mechanism
Menniti, F., Ren, J.-M., Coskran, T. M., Liu, J., Morton, D., Sietsma, D. K., Som, A. T., Stephenson, D., Tate, B., & Finklestein, S. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.156919 · Cited by 43
Chronic Treatment with a Type 5 Phosphodiesterase Inhibitor Suppresses Apoptosis of Corporal Smooth Muscle by Potentiating Akt Signalling in a Rat Model of Diabetic Erectile Dysfunction
Park, K., Ryu, K. S., Li, W. J., Kim, S. W., & Paick, J. (2008) · European Urology · doi:10.1016/j.eururo.2008.01.032 · Cited by 45
Phosphodiesterase-5 Inhibition: the Molecular Biology of Erectile Function and Dysfunction
Francis, S. H., & Corbin, J. D. (2005) · Urologic Clinics of North America · doi:10.1016/j.ucl.2005.08.001 · Cited by 45
Evaluation of neuroprotective and anti-fatigue effects of sildenafil
Uthayathas, S., Karuppagounder, S. S., Ilbasmiş-Tamer, S., Parameshwaran, K., Değim, İ. T., Suppiramaniam, V. D., & Dhanasekaran, M. (2007) · Life Sciences · doi:10.1016/j.lfs.2007.07.018 · Cited by 44
Cellular and molecular mechanisms in vascular repair after traumatic brain injury: a narrative review
Zhao, Z., Yan, L., Wen, J., Satyanarayanan, S. K., Feng, Y., Lu, J., Liu, Y., & Su, H. (2023) · Burns & Trauma · doi:10.1093/burnst/tkad033 · Cited by 45
Pharmacodynamics, pharmacokinetics and clinical efficacy of phosphodiesterase-5 inhibitors
Hong, J. H., Kwon, Y. S., & Kim, I. Y. (2016) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2017.1244265 · Cited by 43
Phosphodiesterase 5 inhibitors as novel agents for the treatment of Alzheimer’s disease
Liu, L., Xu, H., Ding, S., Wang, D., Song, G., & Huang, X. (2019) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2019.09.001 · Cited by 43
Influence of Intravenous Sildenafil on Cerebral Oxygenation Measured by Near-Infrared Spectroscopy in Infants After Cardiac Surgery
Nagdyman, N., Fleck, T., Bitterling, B., Ewert, P., Abdul‐Khaliq, H., Stiller, B., Hübler, M., Lange, P., Berger, F. F., & Schulze‐Neick, I. (2006) · Pediatric Research · doi:10.1203/01.pdr.0000198772.26417.66 · Cited by 43
Sildenafil Decreases BACE1 and Cathepsin B Levels and Reduces APP Amyloidogenic Processing in the SAMP8 Mouse
Orejana, L., Barros-Miñones, L., Jordán, J., Cedazo-Mı́nguez, Á., Tordera, R. M., Aguirre, N., & Puerta, E. (2014) · The Journals of Gerontology Series A · doi:10.1093/gerona/glu106 · Cited by 42
Erythropoietin promotes neurovascular remodeling and long-term functional recovery in rats following traumatic brain injury
Ning, R., Xiong, Y., Mahmood, A., Zhang, Y., Meng, Y., Qu, C., & Chopp, M. (2011) · Brain Research · doi:10.1016/j.brainres.2011.01.099 · Cited by 43
Self-citation
Antidepressant-like effect of sildenafil through oxytocin-dependent cyclic AMP response element-binding protein phosphorylation
Matsushita, H., Matsuzaki, M., Han, X.-J., Nishiki, T.-I., Ohmori, I., Michiue, H., Matsui, H., & Tomizawa, K. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.11.001 · Cited by 42
Penile rehabilitation after radical prostatectomy: does it work?
(2015) · PubMed Central · doi:10.3978/j.issn.2223-4683.2015.02.01 · Cited by 40
Efficacy of Different Nitric Oxide-Based Strategies in Preventing Experimental Cerebral Malaria by Plasmodium berghei ANKA
Martins, Y. C., Zaniní, G. M., Frangos, J. A., & Carvalho, L. J. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032048 · Cited by 42
N europrotection by S ildenafil: N euronal N etworks P otentiation in A cute E xperimental S troke
Chen, X., Wang, N., Zhang, T., Wang, F., Wu, C., & Yang, J. (2013) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12162 · Cited by 41
Sildenafil citrate attenuates a complex maze impairment induced by intracerebroventricular infusion of the NOS inhibitor Nω-nitro-L-arginine methyl ester
Devan, B. D., Pistell, P. J., Daffin, L. W., Nelson, C. M., Duffy, K. B., Bowker, J. L., Bharati, I. S., Sierra‐Mercado, D., Spangler, E. L., & Ingram, D. K. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.02.008 · Cited by 40
Herbal Formula Danggui-Shaoyao-San Promotes Neurogenesis and Angiogenesis in Rat Following Middle Cerebral Artery Occlusion
Ren, C., Wang, B. Z., Li, N., Jin, K., & Ji, X. (2015) · Aging and Disease · doi:10.14336/ad.2014.1126 · Cited by 39
Regenerative Medicine and Stem Cell Based Drug Discovery
Sakurada, K., McDonald, F. M., & Shimada, F. (2008) · Angewandte Chemie International Edition · doi:10.1002/anie.200700724 · Cited by 40
Plant polyphenols in the treatment of age‐associated diseases: Revealing the pleiotropic effects of icariin by network analysis
Schluesener, J. K., & Schluesener, H. J. (2013) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201300409 · Cited by 39
The concept of erectile function preservation (penile rehabilitation) in the patient after brachytherapy for prostate cancer
Stember, D. S., & Mulhall, J. P. (2012) · Brachytherapy · doi:10.1016/j.brachy.2012.01.002 · Cited by 39
Stimulation of Neural Stem Cell Proliferation by Inhibition of Phosphodiesterase 5
Santos, A. I., Carreira, B. P., Nobre, R. J., Carvalho, C. M., & Araújo, I. M. (2014) · Stem Cells International · doi:10.1155/2014/878397 · Cited by 38
Wnt expression in the adult rat subventricular zone after stroke
Morris, D. C., Zhang, Z. G., Wang, Y., Zhang, R. L., Gregg, S. R., Liu, X., & Chopp, M. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2007.03.039 · Cited by 38
Self-citation
Effects of repeated dosing with Udenafil (Zydena) on cognition, somatization and erection in patients with erectile dysfunction: a pilot study
Shim, Y. S., Pae, C.-U., Kim, S. W., Kim, H. W., Kim, J. C., & Koh, J. S. (2011) · International Journal of Impotence Research · doi:10.1038/ijir.2011.13 · Cited by 38
The potential of stem cell therapy for stroke: is PISCES the sign?
Smith, H. K., & Gavins, F. N. E. (2012) · The FASEB Journal · doi:10.1096/fj.11-195719 · Cited by 37
Sildenafil treatment of vascular dementia in aged rats
Venkat, P., Chopp, M., Zacharek, A., Cui, C., Landschoot‐Ward, J., Yu, Q., Chen, Z., & Chen, J. (2018) · Neurochemistry International · doi:10.1016/j.neuint.2018.12.015 · Cited by 37
Self-citation
From Cell Death to Neuronal Regeneration: Building a New Brain after Traumatic Brain Injury
Royo, N. C., Schouten, J. W., Fulp, C. T., Shimizu, S., Marklund, N., Graham, D. I., & McIntosh, T. K. (2003) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/62.8.801 · Cited by 37
Does the endogenous neurogenic response alter behavioral recovery following stroke?
Lagace, D. C. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.08.045 · Cited by 39
Nitric oxide from inflammatory origin impairs neural stem cell proliferation by inhibiting epidermal growth factor receptor signaling
Carreira, B. P., Morte, M. I., Santos, A. I., LourenÃ§o, A. S., sio, A. N. F. A., Carvalho, C. M., & AraÃojo, I. M. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00343 · Cited by 37
Experimental Evidence for Sildenafil's Action in the Central Nervous System: Dopamine and Serotonin Changes in the Medial Preoptic Area and Nucleus Accumbens During Sexual Arousal
Kyratsas, C., Dalla, C., Anderzhanova, E. A., Polissidis, A., Kokras, N., Konstantinides, K., & Papadopoulou‐Daifoti, Z. (2012) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2012.03000.x · Cited by 36
Cell-based therapy for stroke
Luo, Y. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0478-4 · Cited by 35
Effect of sildenafil on the anticonvulsant action of classical and second‐generation antiepileptic drugs in maximal electroshock‐induced seizures in mice
Nieoczym, D., Łuszczki, J. J., Czuczwar, S. J., & Właź, P. (2010) · Epilepsia · doi:10.1111/j.1528-1167.2009.02485.x · Cited by 34
Subacute Intranasal Administration of Tissue Plasminogen Activator Promotes Neuroplasticity and Improves Functional Recovery following Traumatic Brain Injury in Rats
Meng, Y., Chopp, M., Zhang, Y., Liu, Z., Aaron, A., Mahmood, A., & Xiong, Y. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106238 · Cited by 34
Self-citation
Phosphodiesterase inhibition facilitates cognitive restoration in rodent models of age-related memory decline
Devan, B. D., Pistell, P. J., Duffy, K. B., Kelley-Bell, B., Spangler, E. L., & Ingram, D. K. (2014) · Neurorehabilitation · doi:10.3233/nre-131022 · Cited by 34
Brain Remodelling following Endothelin-1 Induced Stroke in Conscious Rats
Abeysinghe, H. C. S., Bokhari, L., Dusting, G. J., & Roulston, C. L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097007 · Cited by 33
Sildenafil acts on the central nervous system increasing sympathetic activity
Fazan, R., Huber, D. A., Silva, C. A. A., da Silva, V. J. D., Salgado, M. C. O., & Salgado, H. C. (2008) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01142.2007 · Cited by 33
The potential therapeutic effect of phosphodiesterase 5 inhibitors in the acute ischemic stroke (AIS)
AlRuwaili, R., Al-Kuraishy, H. M., Alruwaili, M., Khalifa, A. K., Alexiou, A. T., Papadakis, M., Saad, ‏. M., & Batiha, G. E. (2023) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-023-04793-1 · Cited by 32
Sildenafil improves hippocampal brain injuries and restores neuronal development after neonatal hypoxia–ischemia in male rat pups
Yazdani, A., Howidi, B., Shi, M. Z., Tugarinov, N., Khoja, Z., & Wintermark, P. (2021) · Scientific Reports · doi:10.1038/s41598-021-01097-6 · Cited by 32
Cerebral Haemodynamic Response or Excitability is not Affected by Sildenafil
Kruuse, C. R., Hansen, A. E., Larsson, H. B. W., Lauritzen, M., & Rostrup, E. (2009) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2009.10 · Cited by 32
MRI Detects Brain Reorganization after Human Umbilical Tissue-Derived Cells (hUTC) Treatment of Stroke in Rat
Jiang, Q., Thiffault, C., Kramer, B. C., Ding, G., Zhang, L., Nejad‐Davarani, S. P., Li, L., Arbab, A. S., Lü, M., Navia, B., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042845 · Cited by 32
Self-citation
Icariin Ameliorates Neuropathological Changes, TGF-β1 Accumulation and Behavioral Deficits in a Mouse Model of Cerebral Amyloidosis
Zhang, Z., Li, C., Zug, C., & Schluesener, H. J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0104616 · Cited by 33
Self-citation
Exploring the Multifaceted Potential of Sildenafil in Medicine
Pușcașu, C., Zanfirescu, A., Negreș, S., & Șeremet, O. C. (2023) · Medicina · doi:10.3390/medicina59122190 · Cited by 31
Neuroprotective role of PDE4 and PDE5 inhibitors in 3-nitropropionic acid induced behavioral and biochemical toxicities in rats
Thakur, T., Sharma, S., Kumar, K., Deshmukh, R. R., & Sharma, P. L. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.06.035 · Cited by 31
A dose–response study of thymosin β4 for the treatment of acute stroke.
Morris, D. C., Cui, Y., Cheung, W. L., Lu, M., Zhang, L., Zhang, Z. G., & Chopp, M. (2014) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2014.07.006 · Cited by 31
Self-citation
Aggressive behavior increases after termination of chronic sildenafil treatment in mice
Hotchkiss, A. K., Pyter, L. M., Gatien, M. L., WEN, J., Milman, H. A., & Nelson, R. J. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.09.005 · Cited by 31
Yonkenafil: A novel phosphodiesterase type 5 inhibitor induces neuronal network potentiation by a cGMP-dependent Nogo-R axis in acute experimental stroke
Chen, X., Wang, N., Liu, Y., Liu, Y., Zhang, T., Zhu, L., Wang, Y., Wu, C., & Yang, J. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.07.007 · Cited by 31
Self-citation
Longitudinal Magnetic Resonance Imaging of Sildenafil Treatment of Embolic Stroke in Aged Rats
Ding, G., Jiang, Q., Li, L., Zhang, L., Zhang, Z., Lü, M., Li, Q., Gu, S., Ewing, J. R., & Chopp, M. (2011) · Stroke · doi:10.1161/strokeaha.111.622092 · Cited by 31
Self-citation
Targeting nitric oxide in the subacute restorative treatment of ischemic stroke
Zhang, R. L., Zhang, Z. G., & Chopp, M. (2013) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2013.793672 · Cited by 30
Self-citation
Activated protein C analog promotes neurogenesis and improves neurological outcome after focal ischemic stroke in mice via protease activated receptor 1
Wang, Y., Zhao, Z., Chow, N., Ali, T., Griffin, J. H., & Zloković, B. V. (2013) · Brain Research · doi:10.1016/j.brainres.2013.02.023 · Cited by 30
Self-citation
Protective effects of primary neural stem cell treatment in ischemic stroke models
Yu, X., Wang, X., Zeng, S., & Tuo, X. (2018) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2018.6466 · Cited by 30
From Age-Related Cognitive Decline to Alzheimer’s Disease: A Translational Overview of the Potential Role for Phosphodiesterases
Heckman, P. R. A., Blokland, A., & Prickaerts, J. (2017) · Advances in neurobiology · doi:10.1007/978-3-319-58811-7_6 · Cited by 30
The role of sildenafil in the treatment of stroke.
Bednar, M. M. (2008) · PubMed · Cited by 29
Penile Rehabilitation After Prostate Cancer Treatment: Outcomes and Practical Algorithm
Mazzola, C. R., & Mulhall, J. P. (2011) · Urologic Clinics of North America · doi:10.1016/j.ucl.2011.03.002 · Cited by 29
Vascular Abnormalities within Normal Appearing Tissue in Chronic Traumatic Brain Injury
Haber, M., Amyot, F., Kenney, K., Meredith-Duliba, T., Moore, C. B., Silverman, E., Podell, J. E., Chou, Y., Pham, D. L., Butman, J. A., et al. (2018) · Journal of Neurotrauma · doi:10.1089/neu.2018.5684 · Cited by 29
Electric Acupuncture Treatment Promotes Angiogenesis in Rats with Middle Cerebral Artery Occlusion Through EphB4/EphrinB2 Mediated Src/PI3K Signal Pathway
Wu, Y., Hu, R., Zhong, X., Zhang, A., Pang, B., Sun, X., & Zhu, G. (2020) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2020.105165 · Cited by 30
The effects of sildenafil citrate on feto–placental development and haemodynamics in a rabbit model of intrauterine growth restriction
López‐Tello, J., Arias‐Álvarez, M., Martínez, M. D. L. Á. J., Barbero-Fernández, A., García-García, R. M., Rodríguez, M., Lorenzo, P. L., Torres-Rovira, L., Astiz, S., Gonzalez‐Bulnes, A., et al. (2016) · Reproduction Fertility and Development · doi:10.1071/rd15330 · Cited by 29
Phosphodiesterase-5 inhibition promotes remyelination by MCP-1/CCR-2 and MMP-9 regulation in a cuprizone-induced demyelination model.
Nunes, A. K. D. S., Rapôso, C., de Oliveira, W. H., Thomé, R., Verinaud, L., Tovar-Moll, F., & Peixoto, C. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2015.10.013 · Cited by 29
The Role of Sildenafil in Treating Brain Injuries in Adults and Neonates
Xiong, Y., & Wintermark, P. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.879649 · Cited by 27
Repurposing erectile dysfunction drugs tadalafil and vardenafil to increase bone mass
Kim, S., Taneja, C., Pérez‐Peña, H., Ryu, V., Gumerova, A. A., Li, W., Ahmad, N., Zhu, L.-L., Liu, P., Mathew, M., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2000950117 · Cited by 27
The effect of sildenafil citrate (Viagra) on cerebral blood flow in patients with cerebrovascular risk factors
Lorberboym, M., Mena, I. G., Wainstein, J., Boaz, M., & Lampl, Y. (2009) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.2009.01307.x · Cited by 27
Comprehensive Analysis of Sexual Function Outcome in Prostate Cancer Patients After Robot-Assisted Radical Prostatectomy
Woo, S. H., Kang, D. I., Ha, Y., Salmasi, A., Kim, J. H., Lee, D.-H., Kim, W., & Kim, I. Y. (2013) · Journal of Endourology · doi:10.1089/end.2013.0304 · Cited by 27
Differential Contribution of the Guanylyl Cyclase-Cyclic GMP-Protein Kinase G Pathway to the Proliferation of Neural Stem Cells Stimulated by Nitric Oxide
Carreira, B. P., Morte, M. I., Lourenço, A. S., Santos, A. I., Inácio, Â. S., Ambrósio, A. F., Carvalho, C. M., & Araújo, I. M. (2012) · Neurosignals · doi:10.1159/000332811 · Cited by 27
Neuroprotective effect of tadalafil, a PDE-5 inhibitor, and its modulation by L-NAME in mouse model of ischemia-reperfusion injury
Gulati, P., & Singh, N. (2013) · Journal of Surgical Research · doi:10.1016/j.jss.2013.08.005 · Cited by 27
Rewarding properties of sildenafil citrate in mice: role of the nitric oxide-cyclic GMP pathway
Tahsili‐Fahadan, P., Yahyavi‐Firouz‐Abadi, N., Orandi, A. H., Esmaeili, B., Basseda, Z., & Dehpour, A. R. (2006) · Psychopharmacology · doi:10.1007/s00213-005-0302-2 · Cited by 27
Promoting recovery from ischemic stroke
Schmidt, A., & Minnerup, J. (2015) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2016.1134324 · Cited by 27
The Effect of Daily Low Dose Tadalafil on Cerebral Perfusion and Cognition in Patients with Erectile Dysfunction and Mild Cognitive Impairment
Choi, J. B., Cho, K. J., Kim, J. C., Kim, C. H., Chung, Y., Jeong, H. S., Shim, Y. S., & Koh, J. S. (2019) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.2019.17.3.432 · Cited by 26
Impairment of cerebrovascular reactivity in response to hypercapnic challenge in a mouse model of repetitive mild traumatic brain injury
Lynch, C., Eisenbaum, M., Algamal, M., Balbi, M., Ferguson, S., Mouzon, B., Saltiel, N. A., Ojo, J. O., Diaz-Arrastia, R. R., Mullan, M., et al. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20954015 · Cited by 25
Exosomal microRNAs have great potential in the neurorestorative therapy for traumatic brain injury
Yang, Y., Yang, H., Yang, Y., & Ma, Y. (2022) · Experimental Neurology · doi:10.1016/j.expneurol.2022.114026 · Cited by 27
Sildenafil Improves Brain Injury Recovery following Term Neonatal Hypoxia-Ischemia in Male Rat Pups
Yazdani, A., Khoja, Z., Johnstone, A. D., Dale, L., Rampakakis, E., & Wintermark, P. (2016) · Developmental Neuroscience · doi:10.1159/000448327 · Cited by 26
An Old Drug for a New Application: Potential Benefits of Sildenafil in Wound Healing
Farsaie, S., Khalili, H., Karimzadeh, I., & Dashti‐Khavidaki, S. (2012) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.18433/j3tc7v · Cited by 26
Effect of Inducible Nitric Oxide Synthase on Cerebral Blood Flow after Experimental Traumatic Brain Injury in Mice
Foley, L. M., Hitchens, T. K., Melick, J. A., Bayır, H., Ho, C., & Kochanek, P. M. (2008) · Journal of Neurotrauma · doi:10.1089/neu.2007.0471 · Cited by 26
Design and synthesis of 3-aminophthalazine derivatives and structural analogues as PDE5 inhibitors: anti-allodynic effect against neuropathic pain in a mouse model
Bollenbach, M., Lugnier, C., Kremer, M., Salvat, É., Megat, S., Bihel, F. J. ‐., Bourguignon, J., Barrot, M., & Schmitt, M. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.05.026 · Cited by 25
Inhibition of calpain-regulated p35/cdk5 plays a central role in sildenafil-induced protection against chemical hypoxia produced by malonate
Barros-Miñones, L., Martin‐de‐Saavedra, M. D., Perez‐Alvarez, S., Orejana, L., Suquía, V., Goñi‐Allo, B., Hervías, I., López, M. G., Jordán, J., Aguirre, N., et al. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.02.002 · Cited by 25
Caveolin-1 and MLRs: A potential target for neuronal growth and neuroplasticity after ischemic stroke
Zhong, W., Huang, Q., Zeng, L., Hu, Z., & Tang, X. (2019) · International Journal of Medical Sciences · doi:10.7150/ijms.35158 · Cited by 24
Phosphodiesterase 5 inhibitor, zaprinast, selectively increases cerebral blood flow in the ischemic penumbra in the rat brain
Gao, F., Sugita, M., & NUKUI, H. (2005) · Neurological Research · doi:10.1179/016164105x25135 · Cited by 25
Therapeutic effect of sildenafil on blast-induced tinnitus and auditory impairment
Mahmood, G., Mei, Z., Hojjat, H., Pace, E., Kallakuri, S., & Zhang, J. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.03.020 · Cited by 24

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: Wang, Ying
Zhang, Zhenggang
Zhang, Lijie
Chopp, Michael
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

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

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks