title: Methylene Blue Reduces Acute Cerebral Ischemic Injury via the Induction of Mitophagy.
abstract: The treatment of stroke is limited by a short therapeutic window and a lack of effective clinical drugs. Methylene blue (MB) has been used in laboratories and clinics since the 1890s. Few studies have reported the neuroprotective role of MB in cerebral ischemia-reperfusion injury. However, whether and how MB protects against acute cerebral ischemia (ACI) injury was unclear. In this study, we investigated the effect of MB on this injury and revealed that MB protected against ACI injury by augmenting mitophagy. Using a rat middle cerebral artery occlusion (MCAO) model, we demonstrated that MB improved neurological function and reduced the infarct volume and necrosis after ACI injury. These improvements depended on the effect of MB on mitochondrial structure and function. ACI caused the disorder and disintegration of mitochondrial structure, while MB ameliorated the destruction of mitochondria. In addition, mitophagy was inhibited at 24 h after stroke and MB augmented mitophagy. In an oxygen-glucose deprivation (OGD) model in vitro, we further revealed that the elevation of mitochondrial membrane potential (MMP) by MB under OGD conditions mediated the augmented mitophagy. In contrast, exacerbating the decline of MMP during OGD abolished the MB-induced activation of mitophagy. Taken together, MB promotes mitophagy by maintaining the MMP at a relatively high level, which contributes to a decrease in necrosis and an improvement in neurological function, thereby protecting against ACI injury.
authors.affiliation: Department of Cognitive Science, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Di
authors.affiliation: Department of Cognitive Science, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: Yun-Ling
authors.initials: YL
authors.lastname: He
authors.affiliation: Department of Cognitive Science, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Cognitive Science, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Cognitive Science, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: Kui-Wu
authors.initials: KW
authors.lastname: Wu
authors.affiliation: Department of Cognitive Science, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: Shu-Hong
authors.initials: SH
authors.lastname: Liu
authors.affiliation: Department of Cognitive Science, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: Yong-Qi
authors.initials: YQ
authors.lastname: Zhao
authors.affiliation: Department of Cognitive Science, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong, People's Republic of China.|Beijing Institute for Brain Disorders, Beijing, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
authors.affiliation: Department of Cognitive Science, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Wu
authors.affiliation: Department of Cognitive Science, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong, People's Republic of China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D006801:Humans; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008751:Methylene Blue / Q000008:administration & dosage*; D063306:Mitophagy / Q000187:drug effects; D009336:Necrosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D018696:Neuroprotective Agents; D005947:Glucose; D010100:Oxygen; D008751:Methylene Blue