Muscle-derived autologous mitochondrial transplantation: A novel strategy for treating cerebral ischemic injury
Muscle-derived autologous mitochondrial transplantation: A novel strategy for treating cerebral ischemic injury
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肌源性自体线粒体移植：治疗脑缺血损伤的新策略
DOI：
10.1016/j.bbr.2018.09.005
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发表时间：
2019-01-01
影响因子：
2.7
通讯作者：
Wang, Qiang
中科院分区：
文献类型：
--
作者：
Zhang, Zhanqin;Ma, Zhi;Wang, Qiang
现有证据表明，脑卒中后星形胶质细胞向神经元释放含线粒体的细胞外囊泡的线粒体转移具有神经保护作用。细胞外线粒体补充能否挽救脑组织缺血性损伤，仍需进一步探索。我们推测，脑缺血后线粒体损伤的加剧可以通过及时补充外源线粒体来解决。本研究采用大脑中动脉闭塞（MCAO）脑卒中模型来验证这一假设。本研究发现，MCAO后大鼠脑脊液细胞外线粒体数量增加，线粒体比例较高与良好的神经预后相关。缺血90 min后，直接向大鼠侧脑室注入自体来源线粒体（从自体胸大肌分离）或载体，使大鼠恢复4周。在边界区和缺血半暗区可见大量注入的线粒体。此外，线粒体移植可减少脑卒中后细胞氧化应激和凋亡，减轻反应性星形胶质细胞形成，促进神经发生。此外，线粒体移植可减少脑梗死面积并逆转神经功能缺损。研究结果表明，线粒体通过侧脑室的传递导致其广泛分布于整个大脑，并在缺血-再灌注损伤后发挥神经保护作用。
The available evidence showed that mitochondrial transfer by releasing the extracellular vesicles containing mitochondria from astrocytes to neurons exerted a neuroprotective effect after stroke. Whether extracellular mitochondrial replenishment could rescue the tissues from cerebral ischemic injury still needs to be explored completely. It was hypothesized that the augmentation of mitochondrial damage after cerebral ischemia could be resolved by timely replenishment of exogenous mitochondria. A stroke model of middle cerebral artery occlusion (MCAO) was used in this study to verify this hypothesis. This study found that the number of extracellular mitochondria increased in rat cerebrospinal fluid after MCAO, and a higher proportion of mitochondria were associated with good neurological outcomes. Following 90-min ischemia, autologously derived mitochondria (isolated from autologous pectoralis major) or vehicle alone was infused directly into the lateral ventricles, and the rats were allowed to recover for 4 weeks. A plenty of infused mitochondria were found to be distributed in the boundary and ischemic penumbra areas. Furthermore, the transplantation of mitochondria reduced cellular oxidative stress and apoptosis, attenuated reactive astrogliosis, and promoted neurogenesis after stroke. Moreover, the transplantation of mitochondria decreased brain infarct volume and reversed neurological deficits. The findings suggested that the delivery of mitochondria through the lateral ventricles resulted in their widespread distribution throughout the brain and exerted a neuroprotective effect after ischemia-reperfusion injury.