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胰高血糖素样肽-1受体激动剂在创伤性脑损伤中的治疗潜力

The Therapeutic Potential of Glucagon-like Peptide 1 Receptor Agonists in Traumatic Brain Injury.

作者信息

Harej Hrkać Anja, Pilipović Kristina, Belančić Andrej, Juretić Lea, Vitezić Dinko, Mršić-Pelčić Jasenka

机构信息

Department of Basic and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.

Department of Clinical Pharmacology, Clinical Hospital Centre Rijeka, 51000 Rijeka, Croatia.

出版信息

Pharmaceuticals (Basel). 2024 Oct 1;17(10):1313. doi: 10.3390/ph17101313.

Abstract

Traumatic brain injury (TBI), which is a global public health concern, can take various forms, from mild concussions to blast injuries, and each damage type has a particular mechanism of progression. However, TBI is a condition with complex pathophysiology and heterogenous clinical presentation, which makes it difficult to model for in vitro and in vivo studies and obtain relevant results that can easily be translated to the clinical setting. Accordingly, the pharmacological options for TBI management are still scarce. Since a wide spectrum of processes, such as glucose homeostasis, food intake, body temperature regulation, stress response, neuroprotection, and memory, were demonstrated to be modulated after delivering glucagon-like peptide 1 (GLP-1) or GLP-1 receptor agonists into the brain, we aimed to speculate on their potential role in TBI management by comprehensively overviewing the preclinical and clinical body of evidence. Based on promising preclinical data, GLP-1 receptor agonists hold the potential to extend beyond metabolic disorders and address unmet needs in neuroprotection and recovery after TBI, but also other types of central nervous system injuries such as the spinal cord injury or cerebral ischemia. This overview can lay the basis for tailoring new research hypotheses for future in vitro and in vivo models in TBI settings. However, large-scale clinical trials are crucial to confirm their safety and efficacy in these new therapeutic applications.

摘要

创伤性脑损伤(TBI)是一个全球公共卫生问题,它可以有多种形式,从轻度脑震荡到爆炸伤,每种损伤类型都有特定的进展机制。然而,TBI是一种具有复杂病理生理学和异质性临床表现的疾病,这使得在体外和体内研究中对其进行建模并获得能够轻易转化到临床环境中的相关结果变得困难。因此,用于TBI治疗的药物选择仍然很少。由于在将胰高血糖素样肽1(GLP-1)或GLP-1受体激动剂注入大脑后,已证明多种过程,如葡萄糖稳态、食物摄入、体温调节、应激反应、神经保护和记忆等都受到了调节,我们旨在通过全面概述临床前和临床证据来推测它们在TBI治疗中的潜在作用。基于有前景的临床前数据,GLP-1受体激动剂有可能不仅超越代谢紊乱,满足TBI后神经保护和恢复方面未被满足的需求,还能满足脊髓损伤或脑缺血等其他类型中枢神经系统损伤的需求。这一概述可为在TBI环境中为未来的体外和体内模型量身定制新的研究假设奠定基础。然而,大规模临床试验对于确认它们在这些新治疗应用中的安全性和有效性至关重要。

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