title: Delayed Treatment with Green Tea Polyphenol EGCG Promotes Neurogenesis After Ischemic Stroke in Adult Mice.
abstract: (-)-Epigallocatechin-3‑gallate (EGCG), the predominant constituent of green tea, has been demonstrated to be neuroprotective against acute ischemic stroke. However, the long-term actions of EGCG on neurogenesis and functional recovery after ischemic stroke have not been identified. In this study, C57BL/6 mice underwent middle cerebral artery occlusion (60 min) followed by reperfusion for 28 days. Neural progenitor cells (NPCs) were isolated from ipsilateral subventricular zone (SVZ) at 14 days post-ischemia (dpi). The effects of EGCG on the proliferation and differentiation of NPCs were examined in vivo and in vitro. Behavioral assessments were made 3 days before MCAO and at 28 dpi. SVZ NPCs were stimulated with lipopolysaccharide (LPS) in vitro to mimic the inflammatory response after ischemic stroke. We found that 14 days treatment with EGCG significantly increased the proliferation of SVZ NPCs and the migration of SVZ neuroblasts, as well as functional recovery, perhaps through M2 phenotype induction in microglia. LPS stimulation promoted the neuronal differentiation in cultured NPCs from the ischemic SVZ. EGCG treatment (20 or 40 μM) further significantly increased the neuronal differentiation of LPS-stimulated SVZ NPCs. After screening for multiple signaling pathways, the AKT signaling pathway was found to be involved in EGCG-mediated proliferation and neuronal differentiation of NPCs in vitro. Taken together, our results reveal a previously uncharacterized role of EGCG in the augment of proliferation and neuronal differentiation of SVZ NPCs and subsequent spontaneous recovery after ischemic stroke. Thus, the beneficial effects of EGCG on neurogenesis and stroke recovery should be considered in developing therapeutic approaches.
authors.affiliation: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.|Department of Anesthesia & Critical Care Medicine, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
authors.forename: Jian-Cheng
authors.initials: JC
authors.lastname: Zhang
authors.affiliation: Department of Critical Care Medicine, First Affiliated Hospital of the Medical College, Shihezi University, Shihezi City, Xinjiang Uyghur Autonomous Region, 832003, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.|Department of Anesthesia & Critical Care Medicine, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.|Department of Anesthesia & Critical Care Medicine, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.|Department of Anesthesia & Critical Care Medicine, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. franklinyun@hust.edu.cn.|Department of Anesthesia & Critical Care Medicine, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China. franklinyun@hust.edu.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. yuan_shiying@163.com.|Department of Anesthesia & Critical Care Medicine, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China. yuan_shiying@163.com.
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Yuan
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010641:Phenotype; D059808:Polyphenols / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D020521:Stroke / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D059808:Polyphenols; D002392:Catechin; C045651:epigallocatechin gallate; D051057:Proto-Oncogene Proteins c-akt
keywords: (−)-Epigallocatechin-3‑gallate; Ischemic stroke; Neural progenitors; Neurogenesis; Recovery