Inhibition of interleukin-6 abolishes the promoting effects of pair housing on post-stroke neurogenesis.
Interleukin-6 (IL-6) has been shown to promote post-stroke angiogenesis and long-term functional recovery; however, whether IL-6 could promote post-stroke neurogenesis remains unclear. This study aims to investigate the effects of IL-6 on neurogenesis after ischemic stroke. We also investigated whether pair housing (PH) could improve the experimental stroke outcome through IL-6. Transient middle cerebral artery occlusion (tMCAO) was induced in mice treated with recombinant IL-6 (rIL-6) or anti-IL-6 neutralizing antibodies (anti-IL-6 mAbs). Another set of mice were pair-housed (PH; male and ovariectomized female) for 2weeks, subjected to tMCAO and then assigned to a housing condition (isolated or PH). Pair-housed mice were treated with anti-IL-6 mAbs. Behavioral assessments were made 3days before tMCAO and after 28 days of reperfusion. Neural progenitor cells (NPCs) isolated from ipsilateral subventricular zone (SVZ) at 14 days post-ischemia were treated with rIL-6 plus soluble IL-6 receptor (sIL-6R). The effects of IL-6 on the proliferation and differentiation of NPCs were examined in vivo and in vitro. The role and mechanism of IL-6 in PH-mediated enhancement of NPC proliferation and functional recovery were investigated in vivo. We found that anti-IL-6 mAbs significantly reduced the proliferation and neuronal differentiation of NPCs in the ipsilateral SVZ, as well as functional recovery; whereas rIL-6 conferred the opposite effects. PH significantly promoted NPC proliferation and functional recovery compared with socially isolated cohorts; blockade of IL-6 with anti-IL-6 mAbs prevented this promoting effect. In conclusion, our results suggest that IL-6 is an important mediator of social interaction on neurogenesis and long-term functional recovery after ischemic stroke.
Department of Anesthesia, Institute of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
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Meng
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.
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Zhang
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.
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Shi
Department of Anesthesia, Institute of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: zhangshihai@vip.163.com.
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Zhang
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. Electronic address: yuan_shiying@163.com.
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Yuan
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000473:pathology; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D005260:Female; D006798:Housing; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology* / Q000534:rehabilitation*; D015850:Interleukin-6 / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D010052:Ovariectomy; D020127:Recovery of Function
D000906:Antibodies; D000089622:Doublecortin Domain Proteins; D015850:Interleukin-6; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides
IL-6; ischemic stroke; middle cerebral artery occlusion; neural progenitor cells; pair housing