title: Sevoflurane preconditioning induced endogenous neurogenesis against ischemic brain injury by promoting microglial activation.
abstract: Brain ischemia causes irreversible damage to functional neurons in cases of infarct. Promoting endogenous neurogenesis to replace necrotic neurons is a promising therapeutic strategy for ischemia patients. The neuroprotective role of sevoflurane preconditioning implies that it might also enhance endogenous neurogenesis and functional restoration in the infarct region. By using a transient middle cerebral artery occlusion (tMCAO) model, we discovered that endogenous neurogenesis was enhanced by sevoflurane preconditioning. This enhancement process is characterized by the promotion of neuroblast proliferation within the subventricular zone (SVZ), migration and differentiation into neurons, and the presence of astrocytes and oligodendrocytes at the site of infarct. The newborn neurons in the sevoflurane preconditioning group showed miniature excitatory postsynaptic currents (mEPSCs), increased synaptophysin and PSD95 staining density, indicating normal neuronal function. Furthermore, long-term behavioral improvement was observed in the sevoflurane preconditioning group consistent with endogenous neurogenesis. Further histological analyses showed that sevoflurane preconditioning accelerated microglial activation, including migration, phagocytosis and secretion of brain-derived neurotrophic factor (BDNF). Intraperitoneal injection of minocycline, a microglial inhibitor, suppressed microglial activation and reversed neurogenesis. Our data showed that sevoflurane preconditioning promoted microglial activities, created a favorable microenvironment for endogenous neurogenesis and accelerated functional reconstruction in the infarct region.
authors.affiliation: Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, China.
authors.forename: Hexige
authors.initials: H
authors.lastname: Saiyin
authors.affiliation: Department of Anatomy, Histology & Embryology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Jingmo
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Anatomy, Histology & Embryology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai, 200433, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai, 200433, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yu
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D001930:Brain Injuries / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D019194:Ischemic Preconditioning; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D008911:Minocycline / Q000494:pharmacology; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D051381:Rats; D000077149:Sevoflurane
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008738:Methyl Ethers; D000077149:Sevoflurane; D008911:Minocycline
keywords: ischemia and reperfusion; microglia; neurogenesis; sevoflurane preconditioning; stem cells