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GLP-1R Agonist Liraglutide Attenuates Inflammatory Reaction and Neuronal Apoptosis and Reduces Early Brain Injury After Subarachnoid Hemorrhage in Rats

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Abstract

Liraglutide, one of the glucagon-like peptide 1 receptor (GLP-1R) agonists, has been demonstrated to protect brain damage produced by ischemic stroke. However, it remains unknown whether liraglutide attenuates early brain injury after subarachnoid hemorrhage. The present study was performed to explore the effect of liraglutide on early brain injury after subarachnoid hemorrhage in rats, and further investigate the potential mechanisms. Sprague-Dawley rats underwent subarachnoid hemorrhage (SAH) by endovascular perforation, then received subcutaneous injection with liraglutide (50 or 100 μg/kg) or vehicle after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, and Evans Blue extravasation were measured 24 h after SAH. Immunofluorescent staining was performed to detect the extent of microglial activation in rat brain 24 h after SAH. TUNEL staining was performed to evaluate neuronal apoptosis in rat brain of SAH. Expression of GLP-1R, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), Bcl-2, Bax, and cleaved caspase-3 in rat brain were determined by western blot. Expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in rat brain was assessed by ELISA. Neurological dysfunction, brain water content, Evans Blue extravasation, microglial activation, and neuronal apoptosis were significantly reduced by GLP-1R agonist liraglutide. Expression of GLP-1R in rat brain was decreased after SAH, which is significantly elevated by liraglutide. Expression of inflammatory mediates like COX-2, iNOS, TNF-α, and IL-1β was increased after SAH, which were significantly inhibited by liraglutide. Furthermore, SAH caused the elevated expression of pro-apoptotic factors Bax and cleaved caspase-3 in rat brain, both of which were inhibited by liraglutide. In addition, liraglutide reversed the expression of anti-apoptotic protein Bcl-2. Our results demonstrated that liraglutide reduces early brain injury and attenuates inflammatory reaction and neuronal apoptosis in rats of SAH. Liraglutide provides neuroprotection against SAH, which might be associated with the inhibition of inflammation and apoptosis.

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Funding

The Natural Science Foundation of Fujian Province of China (2018J01313), the Project of Medical Innovation of Health and Family Planning Commission of Fujian Province of China (2016-CX-18), the Qihang Foundation Project of Fujian Medical University of China (2017XQ1034), and the Joint Funds for the innovation of science and Technology of Fujian province (2018Y9004) supported this work.

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  1. Xian-kun Tu and Quan Chen are co-first authors who contributed equally to this article.

Authors and Affiliations

  1. Department of Neurosurgery, Fujian Medical University Union Hospital, 29# Xinquan Road, Fuzhou, 350001, Fujian, China

    Xian-kun Tu, Quan Chen, Song Chen, Bin Huang, Bao-gang Ren & Song-sheng Shi

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  1. Xian-kun Tu
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Correspondence to Bao-gang Ren or Song-sheng Shi.

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Tu, Xk., Chen, Q., Chen, S. et al. GLP-1R Agonist Liraglutide Attenuates Inflammatory Reaction and Neuronal Apoptosis and Reduces Early Brain Injury After Subarachnoid Hemorrhage in Rats. Inflammation 44, 397–406 (2021). https://doi.org/10.1007/s10753-020-01344-4

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