title: Immunodeficiency reduces neural stem/progenitor cell apoptosis and enhances neurogenesis in the cerebral cortex after stroke.
abstract: Acute inflammation in the poststroke period exacerbates neuronal damage and stimulates reparative mechanisms, including neurogenesis. However, only a small fraction of neural stem/progenitor cells survives. In this report, by using a highly reproducible model of cortical infarction in SCID mice, we examined the effects of immunodeficiency on reduction of brain injury, survival of neural stem/progenitor cells, and functional recovery. Subsequently, the contribution of T lymphocytes to neurogenesis was evaluated in mice depleted for each subset of T lymphocyte. SCID mice revealed the reduced apoptosis and enhanced proliferation of neural stem/progenitor cells induced by cerebral cortex after stroke compared with the immunocompetent wild-type mice. Removal of T lymphocytes, especially the CD4(+) T-cell population, enhanced generation of neural stem/progenitor cells, followed by accelerated functional recovery. In contrast, removal of CD25(+) T cells, a cell population including regulatory T lymphocytes, impaired functional recovery through, at least in part, suppression of neurogenesis. Our findings demonstrate a key role of T lymphocytes in regulation of poststroke neurogenesis and indicate a potential novel strategy for cell therapy in repair of the central nervous system.
authors.affiliation: Institute for Advanced Medical Sciences, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Orie
authors.initials: O
authors.lastname: Saino
authors.forename: Akihiko
authors.initials: A
authors.lastname: Taguchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagomi
authors.forename: Akiko
authors.initials: A
authors.lastname: Nakano-Doi
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Kashiwamura
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Doe
authors.forename: Nami
authors.initials: N
authors.lastname: Nakagomi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Soma
authors.forename: Hiroo
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: David M
authors.initials: DM
authors.lastname: Stern
authors.forename: Haruki
authors.initials: H
authors.lastname: Okamura
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsuyama
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D002545:Brain Ischemia / Q000473:pathology / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002540:Cerebral Cortex / Q000473:pathology*; D002544:Cerebral Infarction / Q000473:pathology / Q000523:psychology / Q000628:therapy; D007839:Functional Laterality / Q000502:physiology; D007121:Immunocompetence; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy; D020287:In Situ Nick-End Labeling; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D055495:Neurogenesis / Q000502:physiology*; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000637:transplantation*; D020127:Recovery of Function; D013234:Stem Cells / Q000502:physiology*; D020521:Stroke / Q000276:immunology / Q000473:pathology* / Q000628:therapy*
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit; D053148:Caspase 3