Takase Hajime, Liang Anna C, Miyamoto Nobukazu, Hamanaka Gen, Ohtomo Ryo, Maki Takakuni, Pham Loc-Duyen D, Lok Josephine, Lo Eng H, Arai Ken
Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, USA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA; Department of Neurosurgery, Graduate School of Medicine, Yokohama City University, Japan.
Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, USA.
Neurosci Lett. 2018 Mar 6;668:120-125. doi: 10.1016/j.neulet.2018.01.018. Epub 2018 Jan 11.
Oligodendrocyte precursor cells (OPCs) play critical roles in maintaining the number of oligodendrocytes in white matter. Previously, we have shown that oxidative stress dampens oligodendrocyte regeneration after white matter damage, while a clinically proven radical scavenger, edaravone, supports oligodendrocyte repopulation. However, it is not known how edaravone exerts this beneficial effect against oxidative stress. Using in vivo and in vitro experiments, we have examined whether edaravone exhibits direct OPC-protective effects. For in vivo experiments, prolonged cerebral hypoperfusion was induced by bilateral common carotid artery stenosis in mice. OPC damage was observed on day 14 after the onset of cerebral hypoperfusion, and edaravone was demonstrated to decrease OPC death in cerebral white matter. In vitro experiments also confirmed that edaravone reduced oxidative-stress-induced OPC death. Because white matter damage is a major hallmark of many neurological diseases, and OPCs are instrumental in white matter repair after injury, our current study supports the idea that radical scavengers may provide a potential therapeutic approach for white matter related diseases.
少突胶质前体细胞(OPCs)在维持白质中少突胶质细胞的数量方面发挥着关键作用。此前,我们已经表明氧化应激会抑制白质损伤后少突胶质细胞的再生,而一种临床验证有效的自由基清除剂依达拉奉则有助于少突胶质细胞的重新填充。然而,尚不清楚依达拉奉是如何对氧化应激发挥这种有益作用的。通过体内和体外实验,我们研究了依达拉奉是否具有直接保护OPCs的作用。在体内实验中,通过双侧颈总动脉狭窄诱导小鼠长期脑灌注不足。在脑灌注不足发作后的第14天观察到OPC损伤,并且证明依达拉奉可减少脑白质中OPC的死亡。体外实验也证实依达拉奉可减少氧化应激诱导的OPC死亡。由于白质损伤是许多神经疾病的主要特征,并且OPCs在损伤后白质修复中起重要作用,我们目前的研究支持自由基清除剂可能为白质相关疾病提供一种潜在治疗方法的观点。