title: Critical role of astrocytic interleukin-17 A in post-stroke survival and neuronal differentiation of neural precursor cells in adult mice.
abstract: The brain and the immune system interact in complex ways after ischemic stroke, and the long-term effects of immune response associated with stroke remain controversial. As a linkage between innate and adaptive immunity, interleukin-17 A (IL-17 A) secreted from gamma delta (γδ) T cells has detrimental roles in the pathogenesis of acute ischemic stroke. However, to date, the long-term actions of IL-17 A after stroke have not been investigated. Here, we found that IL-17 A showed two distinct peaks of expression in the ischemic hemisphere: the first occurring within 3 days and the second on day 28 after stroke. Our data also showed that astrocyte was the major cellular source of IL-17 A that maintained and augmented subventricular zone (SVZ) neural precursor cells (NPCs) survival, neuronal differentiation, and subsequent synaptogenesis and functional recovery after stroke. IL-17 A also promoted neuronal differentiation in cultured NPCs from the ischemic SVZ. Furthermore, our in vitro data revealed that in primary astrocyte cultures activated astrocytes released IL-17 A via p38 mitogen-activated protein kinase (MAPK). Culture media from reactive astrocytes increased neuronal differentiation of NSCs in vitro. Blockade of IL-17 A with neutralizing antibody prevented this effect. In addition, after screening for multiple signaling pathways, we revealed that the p38 MAPK/calpain 1 signaling pathway was involved in IL-17 A-mediated neurogenesis in vivo and in vitro. Thus, our results reveal a previously uncharacterized property of astrocytic IL-17 A in the maintenance and augment of survival and neuronal differentiation of NPCs, and subsequent synaptogenesis and spontaneous recovery after ischemic stroke.
authors.affiliation: Department of Anesthesia, Institute of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.|Department of Critical Care Medicine, Institute of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Anesthesia, Institute of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.|Department of Critical Care Medicine, Institute of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: J-C
authors.initials: JC
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Yao
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Anesthesia, Institute of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.|Department of Anesthesia, Faculty of Medicine, Benha University, Benha, Egypt.
authors.forename: A F
authors.initials: AF
authors.lastname: Abdelgawad
authors.affiliation: Department of Anesthesia, Institute of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.|Department of Critical Care Medicine, Institute of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: S-L
authors.initials: SL
authors.lastname: Yao
authors.affiliation: Department of Anesthesia, Institute of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.|Department of Critical Care Medicine, Institute of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Yuan
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020381:Interleukin-17 / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000187:drug effects; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D020127:Recovery of Function / Q000187:drug effects; D020521:Stroke / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D011994:Recombinant Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D002154:Calpain