Abstract
Apoptosis is the crucial pathological mechanism following cerebral ischemic injury. Our previous studies demonstrated that clonidine, one agonist of alpha2-adrenergic receptor (α2-AR), could attenuate cerebral ischemic injury in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). However, it’s unclear whether clonidine exerts neuroprotective effects by regulating neuronal apoptosis. In this study, we elucidated whether clonidine can exert anti-apoptotic effects in cerebral ischemic injury, and further explored the possible mechanisms. Neurological deficit score was measured to evaluate the neurological function. TTC staining was used for the measurement of brain infarct size. Hematoxylin-Eosin (HE) staining was applied to examine the cell morphology. TUNEL and DAPI fluorescent staining methods were used to analyze the cell apoptosis in brain tissue. Fluorescence quantitative real-time PCR was performed to assess the gene expression of Caspase-3 and P53. Western blotting assay was applied to detect the protein expression of Caspase-3 and P53. The results showed that clonidine improved neurological function, reduced brain infarct size, alleviated neuronal damage, and reduced the ratio of cell apoptosis in the brain with MCAO/R injury. moreover, clonidine down-regulated the gene and protein expression of Caspase-3 and P53 which were over-expressed after MCAO/R injury. Whereas, yohimbine (one selective α2-AR antagonist) mitigated the anti-apoptosis effects of clonidine, accompanied by reversed gene and protein expression changes. The results indicated that clonidine attenuated cerebral MCAO/R injury via suppressing neuronal apoptosis, which may be mediated, at least in part, by activating α2-AR.
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All data generated or analyzed during this study are included in this article. The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
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We would like to give our sincere gratitude to the reviewers for their constructive comments. This work was supported by the National Natural Science Foundation of China, Zhejiang Province Natural Science Foundation and yichang Medical and Health Research Project.
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This work was supported by grants from National Natural Science Foundation of China (No. 82073824, No. 81371318, No. 82204837), Zhejiang Province Natural Science Foundation (No. LQ23H290004) and Yichang Medical and Health Research Project (No. A22-2-068).
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He, Z., Yin, BK., Wang, K. et al. The alpha2-adrenergic receptor agonist clonidine protects against cerebral ischemia/reperfusion induced neuronal apoptosis in rats. Metab Brain Dis (2024). https://doi.org/10.1007/s11011-024-01354-3
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DOI: https://doi.org/10.1007/s11011-024-01354-3