The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Acute metformin preconditioning confers neuroprotection against focal cerebral ischaemia by pre‐activation of AMPK‐dependent autophagy
Open accessAbstract
Background and Purpose: Recent clinical trials report that metformin, an activator of AMP‐activated protein kinase (AMPK) used to treat type 2 diabetes, significantly reduces the risk of stroke by actions that are independent of its glucose‐lowering effects. However, the underlying molecular mechanisms are not known. Here, we tested the possibility that acute metformin preconditioning confers neuroprotection by pre‐activation of AMPK‐dependent autophagy in a rat model of permanent middle cerebral artery occlusion (p MCAO). Experimental Approach: Male S prague‐D awley rats were pretreated with either vehicle, an AMPK inhibitor, C ompound C, or an autophagy inhibitor, 3‐methyladenine, and were injected with a single dose of metformin (10 mg kg−1, i.p.). Then, AMPK activity and autophagy biomarkers in the brain were assessed. At 24 h after metformin treatment, rats were subjected to p MCAO; infarct volume, neurological deficits and cell apoptosis were evaluated 24 and 96 h later. Key Results: A single dose of metformin significantly activated AMPK and induced autophagy in the brain. The enhanced autophagic activity was inhibited by C ompound C pretreatment. Furthermore, acute metformin preconditioning significantly reduced infarct volume, neurological deficits and cell apoptosis during a subsequent focal cerebral ischaemia. The neuroprotection mediated by metformin preconditioning was fully abolished by C ompound C and partially inhibited by 3‐methyladenine. Conclusions and Implications: These results provide the first evidence that acute metformin preconditioning induces autophagy by activation of brain AMPK, which confers neuroprotection against subsequent cerebral ischaemia. This suggests that metformin, a well‐known hypoglycaemic drug, may have a practical clinical use for stroke prevention.
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Citations
Cites
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
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“However, overactivation of AMPK by a large dose of metformin may lead to prolonged astrocytic glycolysis, which results in a progressive acidosis and inhibits the ability of neurons to use lactate as an energy source, thus contributing to neuronal death (Pellerin and Magistretti, 1994).”
BackgroundBederson, J. B., Pitts, L. H., Tsuji, M., Nishimura, M. C., Davis, R. L., & Bartkowski, H. (1986) · Stroke · doi:10.1161/01.str.17.3.472 · Cited by 2,681
Guidelines for reporting experiments involving animals: the ARRIVE guidelines
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Selective degradation of mitochondria by mitophagy
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Minireview: The AMP-Activated Protein Kinase Cascade: The Key Sensor of Cellular Energy Status
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Pharmacological inhibition of AMP-activated protein kinase provides neuroprotection in stroke
McCullough, L. D., Zeng, Z., Li, H., Landree, L. E., McFadden, J., & Ronnett, G. V. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m409985200 · Cited by 333
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Tsc1 (hamartin) confers neuroprotection against ischemia by inducing autophagy
Papadakis, M., Hadley, G., Xilouri, M., Hoyte, L. C., Nagel, S., McMenamin, M. M., Tsaknakis, G., Watt, S. M., Drakesmith, C. W., Chen, R., et al. (2013) · Nature Medicine · doi:10.1038/nm.3097 · Cited by 232 · cited 1×
“Recently, it has been proposed that autophagy has a protective role in cerebral ischaemia (Viscomi et al., 2012; Wang et al., 2012; Papadakis et al., 2013).”
BackgroundMetformin modulates hyperglycaemia‐induced endothelial senescence and apoptosis through SIRT1
Arunachalam, G., Samuel, S. M., Marei, I., Ding, H., & Triggle, C. R. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12496 · Cited by 221
Cited by
Heras-Sandoval, D., Pérez-Rojas, J. M., Hernández-Damián, J., & Pedraza-Chaverri, J. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2014.08.019 · Cited by 1,091
Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions
Qin, C., Yang, S., Chu, Y.-H., Zhang, H., Pang, X.-W., Chen, L., Zhou, L.-Q., Chen, M., Tian, D.-S., & Wang, W. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01064-1 · Cited by 939
Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles
Galluzzi, L., Bravo-San Pedro, J. M., Levine, B., Green, D. R., & Kroemer, G. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.22 · Cited by 842
Metformin: a review of its potential indications
Wang, Y.-W., He, S.-J., Feng, X., Cheng, J., Luo, Y.-T., Tian, L., & Huang, Q. (2017) · Drug Design, Development and Therapy · doi:10.2147/dddt.s141675 · Cited by 320
Chen, D., Xia, D., Pan, Z., Xu, D., Zhou, Y., Wu, Y., Cai, N., Tang, Q., Wang, C., Yan, M., et al. (2016) · Cell Death & Disease · doi:10.1038/cddis.2016.334 · Cited by 314
Metadata
- Authors
- Jiang, T., Yu, J., Zhu, X., Wang, H., Tan, M., Cao, L., Zhang, Q., Gao, L., Shi, J., Zhang, Y., & Tan, L.
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2014-06-10
- Volume
- 171
- Issue
- 13
- Pages
- 3146-3157
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- OpenAlex
- W1600770312
- Cited by
- 238
- References
- 12
- FWCI
- 16.85
- Type
- journal article
- Language
- en
- Open access
- green
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