Dirnagl Ulrich, Becker Kyra, Meisel Andreas
Department of Neurology, Center for Stroke Research, Charite Universitätsmedizin Berlin, Charitéplatz, D-10098, Berlin, Germany.
Lancet Neurol. 2009 Apr;8(4):398-412. doi: 10.1016/S1474-4422(09)70054-7.
Neuroprotection and brain repair in patients after acute brain damage are still major unfulfilled medical needs. Pharmacological treatments are either ineffective or confounded by adverse effects. Consequently, endogenous mechanisms by which the brain protects itself against noxious stimuli and recovers from damage are being studied. Research on preconditioning, also known as induced tolerance, over the past decade has resulted in various promising strategies for the treatment of patients with acute brain injury. Several of these strategies are being tested in randomised clinical trials. Additionally, research into preconditioning has led to the idea of prophylactically inducing protection in patients such as those undergoing brain surgery and those with transient ischaemic attack or subarachnoid haemorrhage who are at high risk of brain injury in the near future. In this Review, we focus on the clinical issues relating to preconditioning and tolerance in the brain; specifically, we discuss the clinical situations that might benefit from such procedures. We also discuss whether preconditioning and tolerance occur naturally in the brain and assess the most promising candidate strategies that are being investigated.
急性脑损伤患者的神经保护和脑修复仍是尚未满足的主要医学需求。药物治疗要么无效，要么受到不良反应的困扰。因此，人们正在研究大脑自我保护免受有害刺激并从损伤中恢复的内源性机制。在过去十年中，对预处理（也称为诱导耐受）的研究产生了多种治疗急性脑损伤患者的有前景的策略。其中一些策略正在随机临床试验中进行测试。此外，对预处理的研究还催生了在诸如接受脑部手术的患者以及近期有脑损伤高风险的短暂性脑缺血发作或蛛网膜下腔出血患者中预防性诱导保护的想法。在本综述中，我们重点关注与大脑预处理和耐受相关的临床问题；具体而言，我们讨论可能从这些程序中受益的临床情况。我们还讨论了预处理和耐受是否在大脑中自然发生，并评估正在研究的最有前景的候选策略。
