UK Healthcare Pharmacy Services, Lexington, KY, USA.
CNS Drugs. 2012 Jul 1;26(7):613-36. doi: 10.2165/11634020-000000000-00000.
Traumatic brain injury (TBI) affects 1.6 million Americans annually. The injury severity impacts the overall outcome and likelihood for survival. Current treatment of acute TBI includes surgical intervention and supportive care therapies. Treatment of elevated intracranial pressure and optimizing cerebral perfusion are cornerstones of current therapy. These approaches do not directly address the secondary neurological sequelae that lead to continued brain injury after TBI. Depending on injury severity, a complex cascade of processes are activated and generate continued endogenous changes affecting cellular systems and overall outcome from the initial insult to the brain. Homeostatic cellular processes governing calcium influx, mitochondrial function, membrane stability, redox balance, blood flow and cytoskeletal structure often become dysfunctional after TBI. Interruption of this cascade has been the target of numerous pharmacotherapeutic agents investigated over the last two decades. Many agents such as selfotel, pegorgotein (PEG-SOD), magnesium, deltibant and dexanabinol were ineffective in clinical trials. While progesterone and ciclosporin have shown promise in phase II studies, success in larger phase III, randomized, multicentre, clinical trials is pending. Consequently, no neuroprotective treatment options currently exist that improve neurological outcome after TBI. Investigations to date have extended understanding of the injury mechanisms and sites for intervention. Examination of novel strategies addressing both pathological and pharmacological factors affecting outcome, employing novel trial design methods and utilizing biomarkers validated to be reflective of the prognosis for TBI will facilitate progress in overcoming the obstacles identified from previous clinical trials.
创伤性脑损伤（TBI）每年影响着 160 万美国人。损伤的严重程度影响着整体结果和存活的可能性。目前对急性 TBI 的治疗包括手术干预和支持性治疗。颅内压升高的治疗和脑灌注的优化是目前治疗的基石。这些方法并不能直接解决继发性神经后遗症，这些后遗症会导致 TBI 后持续的脑损伤。根据损伤的严重程度，一系列复杂的过程被激活，并产生持续的内源性变化，影响细胞系统和从大脑初始损伤到整体结果。调节钙内流、线粒体功能、膜稳定性、氧化还原平衡、血流和细胞骨架结构的细胞内稳态过程在 TBI 后往往会出现功能障碍。阻断这一级联反应一直是过去二十年研究的众多药物治疗靶点。许多药物，如 selfotel、pegorgotein (PEG-SOD)、镁、deltibant 和 dexanabinol，在临床试验中均无效。虽然孕激素和环孢素在 II 期研究中显示出了希望，但在更大规模的 III 期、随机、多中心临床试验中取得成功仍有待观察。因此，目前没有改善 TBI 后神经预后的神经保护治疗选择。迄今为止的研究扩展了对损伤机制和干预部位的理解。研究新的策略，包括针对影响结果的病理和药理学因素，采用新的试验设计方法，并利用经验证可反映 TBI 预后的生物标志物，将有助于克服从以前的临床试验中发现的障碍取得进展。
