Department of Neurology, University of Erlangen-Nuremberg, Schwabachanlage 6, Erlangen 91054, Germany.
Curr Neuropharmacol. 2018;16(9):1267-1281. doi: 10.2174/1570159X15666170602112851.
Intracerebral hemorrhage (ICH) accounts for up to 15% of all strokes and is characterized by high rates of mortality and morbidity. The post-ICH brain injury can be distinguished in 1) primary, which are caused by disruption and mechanical deformation of brain tissue due to hematoma growth and 2) secondary, which are induced by microglia activation, mitochondrial dysfunction, neurotransmitter and inflammatory mediator release. Although these events typically lead to necrosis, the occurrence of programmed cell death has also been reported after ICH.
We reviewed recent publications describing advance in pre- and clinic ICH research.
At present, treatment of ICH patients is based on oral anticoagulant reversal, management of blood pressure and other medical complications. Several pre-clinical studies showed promising results and demonstrated that anti-oxidative and anti-inflammatory treatments reduced neuronal cell death, however, to date, all of these attempts have failed in randomized controlled clinical trials. Yet, the time frame of administration may be crucial in translation from animal to clinical studies. Furthermore, the latest pre-clinical research points toward the existence of other, apoptosisunrelated forms kinds of programmed cell death.
Our review summarizes current knowledge of pathways leading to programmed cell death after ICH in addition to data from clinical trials. Some of the pre-clinical results have not yet demonstrated clinical confirmation, however they significantly contribute to our understanding of post-ICH pathology and can contribute to development of new therapeutic approaches, decreasing mortality and improving ICH patients' quality of life.
脑出血(ICH)占所有中风的 15%,其死亡率和发病率都很高。ICH 后的脑损伤可分为 1)原发性,由血肿生长引起的脑组织破裂和机械变形引起,2)继发性,由小胶质细胞激活、线粒体功能障碍、神经递质和炎症介质释放引起。尽管这些事件通常导致坏死,但ICH 后也有程序性细胞死亡的发生。
我们回顾了描述 ICH 前和临床研究进展的最新出版物。
目前,ICH 患者的治疗基于口服抗凝剂逆转、血压管理和其他医疗并发症的治疗。一些临床前研究显示出有希望的结果,并表明抗氧化和抗炎治疗可减少神经元细胞死亡,但迄今为止,所有这些尝试在随机对照临床试验中均告失败。然而,从动物到临床研究的转化,给药时间可能是关键。此外,最新的临床前研究表明存在其他与细胞凋亡无关的程序性细胞死亡形式。
我们的综述总结了 ICH 后程序性细胞死亡的途径以及临床试验的数据。一些临床前结果尚未得到临床证实,但它们显著促进了我们对 ICH 后病理学的理解,并有助于开发新的治疗方法,降低死亡率,提高 ICH 患者的生活质量。