Intracerebral hemorrhage (ICH) is a primary cause of death and disability in adults worldwide. Secondary brain injury (SBI) induced by ICH can lead to impaired mitochondrial function, which ultimately contributes to apoptosis and necrosis. Mitochondrial Rho GTPase 1 (Miro1) is a key regulator of mitochondrial movement and motor protein binding. Although Miro1 has been demonstrated to be implicated in various types of central nervous system damage, its potential effect on ICH-induced SBI has not been studied in detail. Hence, in the present new study, we explored the effect of Miro1 on SBI in vivo and in vitro. Self-body heart blood was injected into the right basal ganglia of the rat brain in vivo. Meanwhile, our in vitro model of ICH was based on the stimulation of oxygen hemoglobin (OxyHb) to neurons. Then, Miro1 was overexpressed both in the brains of rats after ICH in vivo and in OxyHb-treated cultured neurons in vitro. Miro1 overexpression in vivo reduced several pathological indexes such as brain edema, neurobehavioral impairment, and neuronal death. Immunofluorescent staining in vitro showed that overexpression of Miro1 ameliorated neuronal damage via facilitation of mitochondrial transport and distribution. JC-1 staining indicated that overexpression of Miro1 reduced the collapse of mitochondrial membrane potential and enhanced mitochondrial mass. Additionally, live-dead cellular staining and flow cytometry analysis revealed that Miro1 overexpression in cultured neurons reduced both necrotic and apoptotic rates. In contrast, inhibition of Miro1 expression yielded opposite effects to those of Miro1 overexpression. Above all, the upregulation of Miro1 significantly alleviated pathological symptoms on SBI in vivo and in vitro.

脑出血 (ICH) 是全球成年人死亡和残疾的主要原因。ICH 诱导的继发性脑损伤 (SBI) 可导致线粒体功能受损，最终导致细胞凋亡和坏死。线粒体 Rho GTPase 1 (Miro1) 是线粒体运动和运动蛋白结合的关键调节因子。尽管 Miro1 已被证明与各种类型的中枢神经系统损伤有关，但尚未详细研究其对 ICH 诱导的 SBI 的潜在影响。因此，在目前的新研究中，我们探讨了 Miro1 在体内和体外对 SBI 的影响。在体内将自体心脏血液注入大鼠大脑的右侧基底神经节。同时，我们的 ICH 体外模型基于氧血红蛋白 (OxyHb) 对神经元的刺激。然后，Miro1 在体内 ICH 后的大鼠脑中和体外经 OxyHb 处理的培养神经元中均过表达。Miro1 体内过表达降低了脑水肿、神经行为障碍和神经元死亡等多项病理指标。体外免疫荧光染色表明，Miro1 的过表达通过促进线粒体转运和分布来改善神经元损伤。JC-1 染色表明 Miro1 的过表达减少了线粒体膜电位的崩溃并增加了线粒体质量。此外，活死细胞染色和流式细胞术分析表明，培养神经元中的 Miro1 过表达降低了坏死和凋亡率。相反，抑制 Miro1 表达产生与 Miro1 过度表达相反的效果。首先，