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Exendin-4 attenuates neuronal death via GLP-1R/PI3K/Akt pathway in early brain injury after subarachnoid hemorrhage in rats
| Content Provider | Scilit |
|---|---|
| Author | Xie, Zhiyi Enkhjargal, Budbazar Wu, Lingyun Zhou, Keren Sun, Chengmei Hu, Xin Gospodarev, Vadim Tang, Jiping You, Chao Zhang, John H. |
| Copyright Year | 2017 |
| Description | Journal: Neuropharmacology Neuronal apoptosis is considered to be a crucial therapeutic target against early brain injury (EBI) after subarachnoid hemorrhage (SAH). Emerging evidence indicates that Exendin-4 (Ex-4), a glucagon-like peptide 1 receptor (GLP-1R) agonist, plays a neuroprotective role in cerebrovascular disease. This study was conducted in order to verify the neuroprotective role of EX-4 in EBI after SAH in rats. The endovascular perforation model of SAH was performed in Sprague-Dawley rats (n = 153). Ex-4 was intraperitoneally injected 1 h after SAH induction in the rats (SAH + Ex-4). To elucidate the underlying molecular mechanism, small interfering ribonucleic acid (siRNA) for GLP-1R and a specific inhibitor of PI3K, LY294002, were injected intracerebroventricularly into SAH + Ex-4 rats before induction of SAH (n = 6 per group). SAH grading evaluation, immunohistochemistry, Western blots, neurobehavioral assessment, and Fluoro-Jade C (FJC) staining experiments were performed. Expression of GLP-1R was significantly increased and mainly expressed in neurons at 24 h after SAH induction. Administration of Ex-4 significantly improved both short- and long-term neurobehavior in SAH + Ex-4 group compared to SAH + Vehicle group after SAH. Ex-4 treatment significantly increased the expression of GLP-1R, PI3K, p-Akt, Bcl-xl, and Bcl-2, while at the same time was found to decrease expression of Bax in the brain. Effects of Ex-4 were reversed by the intervention of GLP-1R siRNA and LY294002 in SAH + Ex-4+GLP-1R siRNA and SAH + Ex-4+LY294002 groups, respectively. In conclusion, the neuroprotective effect of Ex-4 in EBI after SAH was mediated by attenuation of neuronal apoptosis via GLP-1R/PI3K/Akt signaling pathway, therefore EX-4 should be further investigated as a potential therapeutic agent in stroke patients. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714662/pdf |
| Ending Page | 151 |
| Page Count | 10 |
| Starting Page | 142 |
| ISSN | 00283908 |
| e-ISSN | 18737064 |
| DOI | 10.1016/j.neuropharm.2017.09.040 |
| Journal | Neuropharmacology |
| Volume Number | 128 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2017-10-04 |
| Access Restriction | Open |
| Subject Keyword | Journal: Neuropharmacology Behavioral Sciences Subarachnoid Hemorrhage Neuronal Apoptosis Pi3k/akt Signaling |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Cellular and Molecular Neuroscience |
