Hiskens Matthew I, Schneiders Anthony G, Fenning Andrew S
Mackay Institute of Research and Innovation, Mackay Hospital and Health Service, Mackay, QLD 4740, Australia.
School of Health, Medical and Applied Sciences, Central Queensland University, Rockhampton, QLD 4701, Australia.
Biomedicines. 2024 Aug 22;12(8):1930. doi: 10.3390/biomedicines12081930.
Traumatic brain injury (TBI) is a significant contributor to mortality and morbidity in people, both young and old. There are currently no approved therapeutic interventions for TBI. Following TBI, cyclooxygenase (COX) enzymes generate prostaglandins and reactive oxygen species that perpetuate inflammation, with COX-1 and COX-2 isoforms providing differing responses. Selective COX-2 inhibitors have shown potential as neuroprotective agents. Results from animal models of TBI suggest potential treatment through the alleviation of secondary injury mechanisms involving neuroinflammation and neuronal cell death. Additionally, early clinical trials have shown that the use of celecoxib improves patient mortality and outcomes. This review aims to summarize the therapeutic effects of COX-2 inhibitors observed in TBI animal models, highlighting pertinent studies elucidating molecular pathways and expounding upon their mechanistic actions. We then investigated the current state of evidence for the utilization of COX-2 inhibitors for TBI patients.
创伤性脑损伤(TBI)是导致各年龄段人群死亡和发病的重要因素。目前尚无经批准用于TBI的治疗干预措施。TBI后,环氧化酶(COX)生成前列腺素和活性氧,使炎症持续存在,其中COX-1和COX-2亚型表现出不同的反应。选择性COX-2抑制剂已显示出作为神经保护剂的潜力。TBI动物模型的结果表明,通过减轻涉及神经炎症和神经元细胞死亡的继发性损伤机制可能实现治疗。此外,早期临床试验表明,使用塞来昔布可改善患者死亡率和预后。本综述旨在总结在TBI动物模型中观察到的COX-2抑制剂的治疗效果,突出阐明分子途径的相关研究,并阐述其作用机制。然后,我们研究了将COX-2抑制剂用于TBI患者的现有证据状况。