Sevoflurane preconditioning induced endogenous neurogenesis against ischemic brain injury by promoting microglial activation
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Li Li1,*, Hexige Saiyin2,*, Jingmo Xie3, Lixiang Ma3, Lei Xue4, Wei Wang4, Weimin Liang1, Qiong Yu1
1Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, 200040, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, China
3Department of Anatomy, Histology & Embryology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
4Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai, 200433, China
*These authors have contributed equally to this work
Qiong Yu, email: email@example.com
Weimin Liang, email: firstname.lastname@example.org
Keywords: ischemia and reperfusion, microglia, neurogenesis, sevoflurane preconditioning, stem cells
Received: October 24, 2016 Accepted: January 10, 2017 Published: February 14, 2017
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.
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