The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Resveratrol Prevents CA1 Neurons against Ischemic Injury by Parallel Modulation of Both GSK-3β and CREB through PI3-K/Akt Pathways
Abstract
Accumulating evidence indicates that resveratrol potently protects against cerebral ischemia damage due to its oxygen free radicals scavenging and antioxidant properties. However, cellular mechanisms that may underlie the neuroprotective effects of resveratrol in brain ischemia are not fully understood yet. This study aimed to investigate the potential association between the neuroprotective effect of resveratrol and the apoptosis/survival signaling pathways, in particular the glycogen synthase kinase 3 (GSK‐3β) and cAMP response element‐binding protein (CREB) through phosphatidylinositol 3‐kinase (PI3‐K)‐dependent pathway. An experimental model of global cerebral ischemia was induced in rats by the four‐vessel occlusion method for 10 min and followed by different periods of reperfusion. Nissl staining indicated extensive neuronal death at 7 days after ischemia/reperfusion. Administration of resveratrol by i.p. injections (30 mg/kg) for 7 days before ischemia significantly attenuated neuronal death. Both GSK‐3β and CREB appear to play a critical role in resveratrol neuroprotection through the PI3‐K/Akt pathway, as resveratrol pretreatment increased the phosphorylation of Akt, GSK‐3β and CREB in 1 h in the CA1 hippocampus after ischemia/reperfusion. Furthermore, administration of LY294002, an inhibitor of PI3‐K, compromised the neuroprotective effect of resveratrol and decreased the level of p‐Akt, p‐GSK‐3β and p‐CREB after ischemic injury. Taken together, the results suggest that resveratrol protects against delayed neuronal death in the hippocampal CA1 by maintaining the pro‐survival states of Akt, GSK‐3β and CREB pathways. These data suggest that the neuroprotective effect of resveratrol may be mediated through activation of the PI3‐K/Akt signaling pathway, subsequently downregulating expression of GSK‐3β and CREB, thereby leading to prevention of neuronal death after brain ischemia in rats.
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“As an antioxidant agent, RSV can scavenge free radicals and reduce ROS formation, by inhibiting the expression of NADPH and glycogen synthase kinase 3 beta proteins, and upregulating the expression of some antioxidant enzymes, such as SOD2, CAT, GPx, and thioredoxin [320,339,340].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [340]
Citations
Cites
2 retracted
Pharmacological preconditioning with resveratrol: role of nitric oxide
Hattori, R., Otani, H., Maulik, N., & Das, D. K. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01012.2001 · Cited by 202
RetractedDas, S., Fraga, C. G., & Das, D. K. (2006) · Free Radical Research · doi:10.1080/10715760600833085 · Cited by 112
RetractedCREB: A Stimulus-Induced Transcription Factor Activated by A Diverse Array of Extracellular Signals
Shaywitz, A. J., & Greenberg, M. E. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.821 · Cited by 2,133
Sirtuin activators mimic caloric restriction and delay ageing in metazoans
Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M., & Sinclair, D. (2004) · Nature · doi:10.1038/nature02789 · Cited by 1,868
The glamour and gloom of glycogen synthase kinase-3
Jope, R. S., & Johnson, G. V. W. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2003.12.004 · Cited by 1,535
The multifaceted roles of glycogen synthase kinase 3β in cellular signaling
Grimes, C. A., & Jope, R. S. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(01)00011-9 · Cited by 1,440
CREB Is a Regulatory Target for the Protein Kinase Akt/PKB
Du, K., & Montminy, M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.49.32377 · Cited by 952
Resveratrol as an anti-inflammatory and anti-aging agent: Mechanisms and clinical implications
Alarcón‐de‐la‐Lastra, C., & Villegas, I. (2005) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200500022 · Cited by 713
Resveratrol protects against global cerebral ischemic injury in gerbils
Wang, Q., Xu, J., Rottinghaus, G. E., Simonyi, Á., Lubahn, D. E., Sun, G. Y., & Sun, A. Y. (2002) · Brain Research · doi:10.1016/s0006-8993(02)03543-6 · Cited by 528
Is CREB a key to neuronal survival?
Walton, M. R., & Dragunow, M. (2000) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01500-3 · Cited by 520
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Nayak, P. K. (2013) · Otago University Research Archive (University of Otago) · Cited by 1
Inhibition of Phosphodiesterases as A Strategy for Treatment of Spinal Cord Injury
Nikulina, E., & Filbin, M. (2014) · doi:10.1002/9781118836507.ch13
Red wine extract, resveratrol, on maintenance of organ function following trauma-hemorrhage
Liu, F.-C., & Yu, H. (2012) · Functional Foods in Health and Disease · doi:10.31989/ffhd.v2i10.76
“Activation of PI3K/Akt signaling cascade by resveratrol has been observed in different tissues [30,67-69].”
BackgroundGirbovan, C. (2015) · uO Research (University of Ottawa) · doi:10.20381/ruor-2810
Neuroprotective Effect of Resveratrol in Cerebral Ischemia
Ghosh, N., Ghosh, R., Mandal, S. C., & Pal, M. (2017) · doi:10.1002/9781119155195.ch20
Xu, X., Sun, H., Wang, Y., Chen, P., Hu, W., Wo, J., Jia, S., Liu, S., Lü, F., & Liu, S. (2023) · Research Square · doi:10.21203/rs.3.rs-3251187/v1
Zhou, Q., Yang, C., Ren, Y., Ma, Q., Yang, Y., Wang, L., & Chen, G. (2024) · Aquaculture · doi:10.1016/j.aquaculture.2024.740772
Hu, B., Zhao, C., Pan, X., Wei, H., Mo, G., Xian, M., Luo, W., Nie, Q., Li, H., & Zhang, X. (2023) · Figshare · doi:10.6084/m9.figshare.23542913
Hu, B., Zhao, C., Pan, X., Wei, H., Mo, G., Xian, M., Luo, W., Nie, Q., Li, H., & Zhang, X. (2023) · Figshare · doi:10.6084/m9.figshare.23542910
Noori, T., Hosseini, S. Z., Alavi, S. D., Sureda, A., & Shirooie, S. (2026) · Current Neuropharmacology · doi:10.2174/011570159x388575251126041202
“Moreover, evidence from a study in male rats suggests that stimulating the PI3K/AKT signaling pathway with 30 mg/kg of resveratrol may provide neuroprotection by preventing neuronal death following cerebral ischemia [114].”
Metadata
- Authors
- Simão, F., Matté, A., Pagnussat, A. S., Netto, C. A., & Salbego, C. G.
- Affiliations
- Universidade Federal do Rio Grande do Sul (BR)
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2012-07-22
- Volume
- 36
- Issue
- 7
- Pages
- 2899-2905
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W1939636416
- Cited by
- 111
- References
- 45
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 10 · 2023: 5 · 2022: 7 · 2021: 11 · 2020: 7 · 2019: 3 · 2018: 4 · 2017: 9 · 2016: 10 · 2015: 15 · 2014: 10 · 2013: 7 · 2012: 3
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroprotection in Cerebral Ischemia
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- resveratrol, neuroprotection, cerebral ischemia, ischemia-reperfusion injury, hippocampal CA1, GSK3β, CREB, PI3K/Akt signaling, Akt phosphorylation, neuronal cell death, delayed neuronal death, LY294002, four-vessel occlusion
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Resveratrol, Phosphoinositide-3 Kinase Inhibitors, Animals, Brain Ischemia, Chromones, Male, Morpholines, Neurons, Phosphorylation, Stilbenes, Signal Transduction, Reperfusion Injury, Rats, Wistar, Apoptosis, Cyclic AMP Response Element-Binding Protein, Neuroprotective Agents, Phosphatidylinositol 3-Kinases, Glycogen Synthase Kinase 3, Proto-Oncogene Proteins c-akt, Rats, CA1 Region, Hippocampal
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