Photobiomodulation for Global Cerebral Ischemia: Targeting Mitochondrial Dynamics and Functions.
Photobiomodulation for Global Cerebral Ischemia: Targeting Mitochondrial Dynamics and Functions.
复制标题
全球脑缺血的光生物调节：针对线粒体动力学和功能。
DOI：
10.1007/s12035-018-1191-9
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发表时间：
2019-03
影响因子：
5.1
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Wang R;Dong Y;Lu Y;Zhang W;Brann DW;Zhang Q
低温是目前唯一被批准治疗心脏骤停后全脑缺血（GCI）的疗法；然而，不幸的是它有多种不利影响。作为一种非侵入性手术，光生物调节（PBM）疗法已成为脑损伤的潜在新型治疗方法。 PBM 涉及使用低强度激光疗法来影响细胞行为。在这项研究中，我们评估了 GCI 后 6 小时开始使用 808 nm 二极管激光进行 PBM 治疗的治疗效果。值得注意的是，PBM 剂量依赖性地保护脆弱海马 CA1 亚区免受 GCI 诱导的神经元死亡。功能评估表明，PBM 在 GCI 后显着保留了短期（一周）和长期（六个月）的空间学习和记忆功能。进一步的机制研究表明，PBM 后处理：（a）通过减少有害的 Drp1 GTPase 活性及其与接头蛋白 Mff 和 Fis1 的相互作用，并通过平衡线粒体靶向裂变和融合蛋白水平，保持健康的线粒体动力学并抑制 CA1 神经元的大量线粒体碎片； (b) 减少线粒体氧化损伤和过度线粒体自噬，恢复线粒体整体健康状态并保留线粒体功能； (c) 抑制线粒体依赖性凋亡体形成/caspase-3/9 凋亡处理活性。此外，我们在体外缺血模型中验证了细胞色素 c 氧化酶是线粒体功能保存和神经保护的关键 PBM 靶标。我们的研究结果表明，PBM 是 GCI 后功能恢复的一种有前途的治疗策略，其机制涉及 PBM 对线粒体动力学和功能的保护以及抑制 GCI 中延迟性凋亡神经元死亡。
Hypothermia is currently the only approved therapy for global cerebral ischemia (GCI) after cardiac arrest; however, it unfortunately has multiple adverse effects. As a noninvasive procedure, photobiomodulation (PBM) therapy has emerged as a potential novel treatment for brain injury. PBM involves the use of low level laser light therapy to influence cell behavior. In this study, we evaluated the therapeutic effects of PBM treatment with an 808 nm diode laser initiated 6 h after GCI. It was noted that PBM dose-dependently protected against GCI-induced neuronal death in the vulnerable hippocampal CA1 subregion. Functional assessments demonstrated that PBM markedly preserved both short-term (a week) and long-term (six months) spatial learning and memory function following GCI. Further mechanistic studies revealed that PBM post-treatment: (a) preserved healthy mitochondrial dynamics and suppressed substantial mitochondrial fragmentation of CA1 neurons, by reducing the detrimental Drp1 GTPase activity and its interactions with adaptor proteins Mff and Fis1, and by balancing mitochondrial targeting fission and fusion protein levels; (b) reduced mitochondrial oxidative damage and excessive mitophagy, and restored mitochondrial overall health status and preserved mitochondrial function; and (c) suppressed mitochondria-dependent apoptosome formation/caspase-3/9 apoptosis-processing activities. Additionally, we validated, in an in vitro ischemia model, that cytochrome c oxidase served as a key PBM target for mitochondrial function preservation and neuroprotection. Our findings suggest that PBM serves as a promising therapeutic strategy for the functional recovery after GCI, with mechanisms involving PBM’s preservation on mitochondrial dynamics and functions and the inhibition of delayed apoptotic neuronal death in GCI.
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影响因子：
2.8
作者：
Huang, Ying-Ying;Nagata, Kazuya;Tedford, Clark E.;Hamblin, Michael R.
通讯作者：
Hamblin, Michael R.
影响因子：
3.5
作者：
Cartron, Pierre-Francois;Bellot, Gregory;Vallette, Francois M.
通讯作者：
Vallette, Francois M.
影响因子：
12.7
作者：
KIRINO, T;SANO, K
通讯作者：
SANO, K
影响因子：
21.3
作者：
Bleazard, W;McCaffery, JM;Shaw, JM
通讯作者：
Shaw, JM
影响因子：
2.5
作者：
Agrawal, Tanupriya;Gupta, Gaurav K.;Hamblin, Michael R.
通讯作者：
Hamblin, Michael R.