Tashiro Ryosuke, Kitamura Yuki, Bautista-Garrido Jesus, Sun Guanghua, Kim Gab Seok, Aronowski Jaroslaw, Jung Joo Eun
Department of Neurology, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, Texas, USA.
Neuroreport. 2025 Jul 2;36(10):547-554. doi: 10.1097/WNR.0000000000002175. Epub 2025 May 13.
We recently demonstrated that systemically transplanted astrocytic mitochondria enter the intracerebral hemorrhage (ICH)-affected brain, where they protect the neurons by mitigating oxidative damage via upregulation of the manganese superoxide dismutase (Mn-SOD), ultimately contributing to functional recovery after ICH in mice. Although our previous study clearly demonstrated the beneficial effects of mitochondria within the brain, the effect of transferred mitochondria on the peripheral system was not yet studied. Thus, here, we studied the impact of astrocytic mitochondria transfer on post-ICH recovery and modulation of systemic immune responses.
We used the autologous blood injection model for the mouse ICH surgery. Mice subjected to ICH received astrocytic mitochondria intravenously at 1 h, 7, and 14 days post-ICH onset, and the splenic immune responses of these mice were analyzed at 21 days. An ICH-like injury was induced in vitro using primary cultured neurons treated with recombinant interleukin-10, and cell viability, reactive oxygen species levels, and gene expressions were analyzed.
We demonstrate that systemic transplantation of astrocytic mitochondria increases the population of splenic B cells, production of interleukin-10 by B cells, and plasma interleukin-10 levels in mice after ICH. Furthermore, in the ICH-like injury in vitro , exogenous interleukin-10 (to model spleen-mediated interleukin-10 increase) upregulated Mn-SOD expression in the cultured neurons and promoted neuronal survival and neuroplasticity-related gene expressions, suggesting interleukin-10 role in cytoprotection and repair/recovery under ICH-like condition.
Thus, systemic transfer of astrocytic mitochondria modulates post-ICH peripheral immune responses, which may participate in functional recovery.
我们最近证明，全身移植的星形胶质细胞线粒体可进入脑出血（ICH）影响的大脑，通过上调锰超氧化物歧化酶（Mn-SOD）减轻氧化损伤来保护神经元，最终促进小鼠脑出血后的功能恢复。尽管我们之前的研究清楚地证明了脑内线粒体的有益作用，但转移的线粒体对周围系统的影响尚未得到研究。因此，在这里，我们研究了星形胶质细胞线粒体转移对脑出血后恢复和全身免疫反应调节的影响。
我们使用自体血注射模型进行小鼠脑出血手术。脑出血小鼠在脑出血发作后1小时、7天和14天静脉注射星形胶质细胞线粒体，并在21天分析这些小鼠的脾脏免疫反应。使用重组白细胞介素-10处理的原代培养神经元在体外诱导类似ICH的损伤，并分析细胞活力、活性氧水平和基因表达。
我们证明，星形胶质细胞线粒体的全身移植增加了小鼠脑出血后脾脏B细胞的数量、B细胞产生白细胞介素-10的量以及血浆白细胞介素-10水平。此外，在体外类似ICH的损伤中，外源性白细胞介素-10（模拟脾脏介导的白细胞介素-10增加）上调了培养神经元中Mn-SOD的表达，并促进了神经元存活和神经可塑性相关基因的表达，表明白细胞介素-10在类似ICH条件下的细胞保护和修复/恢复中发挥作用。
因此，星形胶质细胞线粒体的全身转移调节了脑出血后的外周免疫反应，这可能参与功能恢复。
