Mdivi-1 alleviates brain damage and synaptic dysfunction after intracerebral hemorrhage in mice
Mdivi-1 alleviates brain damage and synaptic dysfunction after intracerebral hemorrhage in mice
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DOI：
10.1007/s00221-021-06089-6
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发表时间：
2021-03
影响因子：
2
通讯作者：
Yunge Zhang;Tongyu Rui;Chengliang Luo;Qianqian Li
中科院分区：
文献类型：
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作者：
Yunge Zhang;Tongyu Rui;Chengliang Luo;Qianqian Li
线粒体分裂抑制因子1(MDIVI-1)是线粒体分裂蛋白Dynamin-Related Protein-1(Drp1)的选择性抑制因子，可通过血脑屏障发挥神经保护作用。然而，目前尚不清楚MDIVI-1是否能减轻脑出血(ICH)所致的继发性脑损伤。本研究旨在研究脑出血后mdivi-1在小鼠短期和长期行为结果中的作用，以及突触可塑性的变化。结果表明，MDIVI-1逆转了DRp1易位和线粒体的形态变化，并能明显改善短期神经行为缺陷、血脑屏障破坏和脑水肿。此外，MDIVI-1还可改善脑出血所致的运动和记忆功能障碍。MDIVI-1还可以阻止脑出血引起的突触蛋白(突触蛋白I，PSD95)和磷酸化cAMP反应元件结合(p-CREB)的减少。在体外，mdivi-1抑制氯化高铁血红素诱导的海马神经元死亡，并促进轴突生长。综上所述，我们发现MDIVI-1可以缓解短期和长期神经功能缺失、突触功能障碍。这些结果表明，MDIVI-1在治疗脑出血引起的继发性脑损伤、突触功能障碍和神经转归方面可能是有益的。
As a selective inhibitor of mitochondrial fission protein dynamin-related protein-1 (Drp1), mitochondrial division inhibitor 1 (mdivi-1) can cross the blood–brain barrier (BBB) and exert neuroprotection. However, it remains unclear whether mdivi-1 can attenuate intracerebral hemorrhage (ICH)-induced secondary brain injury. This study was undertaken to characterize the roles of mdivi-1 in short-term and long-term behavioral outcomes, along with synaptic plasticity changes in mice after ICH. The results indicated mdivi-1 reversed Drp1 translocation and the morphologic changes of mitochondria, as well as ameliorated short-term neurobehavioral deficits, the BBB disruption and brain edema remarkably. In addition, mdivi-1 could rescue ICH-induced motor and memory dysfunctions. Mdivi-1 could also prevent ICH-induced reductions in synaptic proteins (synapsin I, PSD95) and phosphorylated cAMP-response element binding (p-CREB). In vitro, mdivi-1 inhibited hemin-induced hippocampal neuron death and improved neurite outgrowth. In conclusion, we found that mdivi-1 can alleviate short-term and long-term neurological deficits, synaptic dysfunction. These findings demonstrate that mdivi-1 may be beneficial in the treatment of secondary brain injury, synaptic dysfunction and neurological outcomes caused by ICH.