Clinical treatments for mitochondrial dysfunctions after brain injury
Clinical treatments for mitochondrial dysfunctions after brain injury
复制标题
脑损伤后线粒体功能障碍的临床治疗
DOI：
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发表时间：
2006
影响因子：
3.3
通讯作者：
R. Bullock
中科院分区：
文献类型：
--
作者：
Amedeo Merenda;R. Bullock
综述的目的本综述提供了一个全面的证据支持线粒体功能障碍的作用，促进神经元死亡后急性脑损伤，并严格讨论了最近提出的治疗，可以限制这种功能障碍对神经系统的结果的有害影响。最新发现急性脑损伤后，钙稳态的破坏，活性氧的过度产生，以及线粒体通透性转换孔的开放，是促进线粒体功能障碍的关键因素，并随之激活坏死或凋亡细胞死亡途径。越来越多的兴趣集中在开发能够对抗这些机制的新的治疗策略上。目前正在研究几种药物，包括新型钙通道阻滞剂和抗氧化剂、解偶联蛋白和线粒体渗透性转换孔抑制剂。虽然“灵丹妙药”尚未确定，但临床前和临床研究的结果令人鼓舞。直接针对线粒体功能障碍的过程和机制的治疗干预，可能会为脑损伤患者提供神经保护。然而，线粒体功能障碍的多因素原因表明，需要进一步研究，旨在阐明药物给药的最佳剂量和时间，以及这些方法的逻辑组合/顺序，最终可能实现神经学结局的改善。
Purpose of reviewThis review provides a comprehensive look at the evidence supporting the role of mitochondrial dysfunction in promoting neuronal death after acute brain injury, and critically discusses the most recent proposed therapies that could limit the deleterious effects of such a dysfunction on neurological outcome. Recent findingsFollowing acute brain injury, disruption of calcium homeostasis, overproduction of reactive oxygen species, and opening of the mitochondrial permeability transition pore, are key factors in promoting mitochondrial dysfunction, with ensuing activation of either necrotic or apoptotic cell death pathways. Growing interest has been focused on developing new therapeutic strategies able to oppose these mechanisms. Several pharmacological agents are currently under investigation, including novel calcium channel blockers and antioxidants, uncoupling proteins and mitochondrial permeability transition pore inhibitors. Although a ‘magic bullet’ has not yet been identified, the results of both preclinical and clinical studies are encouraging. SummaryTherapeutic interventions directly targeting processes and mechanisms responsible for mitochondrial dysfunction, may offer neuroprotection in brain-injured patients. The multifactorial cause of mitochondrial dysfunction suggests, however, the need for further studies aimed at clarifying optimal dose and time for drug administration, as well as the logical combination/sequence of those approaches that may ultimately achieve improvement in neurological outcome.
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影响因子：
4.2
作者：
J. Levasseur;B. Alessandri;M. Reinert;R. Bullock;H. Kontos
通讯作者：
J. Levasseur;B. Alessandri;M. Reinert;R. Bullock;H. Kontos
影响因子：
4.2
作者：
Alessandri, B;Rice, AC;Bullock, MR
通讯作者：
Bullock, MR
环孢素 A 延迟皮质神经元中 N-甲基-D-天冬氨酸诱导的线粒体去极化：线粒体通透性转变的证据。
影响因子：
3.3
作者：
Nieminen,AL;Petrie,TG;Lemasters,JJ;Selman,WR
通讯作者：
Selman,WR
影响因子：
4.2
作者：
Signoretti, S;Marmarou, A;Vagnozzi, R
通讯作者：
Vagnozzi, R
DOI：
10.1016/0006-291x(89)92644-2
发表时间：
1989-06-15
影响因子：
3.1
作者：
IGBAVBOA, U;ZWIZINSKI, CW;PFEIFFER, DR
通讯作者：
PFEIFFER, DR