title: Absence of Sema4D improves oligodendrocyte recovery after cerebral ischemia/reperfusion injury in mice.
abstract: Sema4D, originally identified as a negative regulator of axon guidance during development, is involved in various physiological and pathological responses. In this study, we evaluated the effect of Sema4D-deficiency on oligodendrocyte restoration after the cerebral ischemia/reperfusion using direct ligation of the middle cerebral artery followed by reperfusion. In both Sema4D(+/+) wild-type and Sema4D(-/-) null mutant mice, the peri-infarct area showed a decrease in the number of oligodendrocytes at 3 days post-reperfusion. Subsequently, the number of oligodendrocytes was observed to gradually recover in both groups. Sema4D-deficient mice, however, showed an enhanced recovery of oligodendrocytes and an upregulation of oligodendrocyte progenitor cells at days 14 and 28 of reperfusion. Cell proliferation identified by incorporation of bromodeoxyuridine was enhanced in Sema4D(-/-) mice from days 3 to 14 post-reperfusion compared to the Sema4D(+/+) mice. Furthermore, apoptotic cell death of oligodendrocytes was reduced at days 7 post-reperfusion in Sema4D(-/-) mice compared to Sema4D(+/+) mice. These findings indicate that enhanced proliferation of progenitor cells and survival of oligodendrocytes resulted in improved oligodendrocyte recovery in Sema4D(-/-) mice. This may provide a new approach for neurorestorative treatment in patients with stroke, which aims to manipulate endogenous oligodendrogenesis and thereby to promote brain repair after stroke.
authors.affiliation: Group of Neurobiology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan; Division of Pathogenesis and Control of Oral Diseases, Graduate School of Dentistry, Osaka University, 565-0871, Japan.
authors.forename: Takenobu
authors.initials: T
authors.lastname: Wada
authors.affiliation: Group of Neurobiology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Sawano
authors.affiliation: Group of Neurobiology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Liberal Arts and Sciences, Kagawa Prefectural University of Health Sciences, Takamatsu, Kagawa 761-0123, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Furuyama
authors.affiliation: Group of Neurobiology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Moe
authors.initials: M
authors.lastname: Fukumoto
authors.affiliation: Group of Neurobiology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Yamaguchi
authors.affiliation: Group of Neurobiology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan; Laboratory of Neurogenesis and CNS Repair, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: Orie
authors.initials: O
authors.lastname: Saino
authors.affiliation: Group of Neurobiology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan; Division of Pathogenesis and Control of Oral Diseases, Graduate School of Dentistry, Osaka University, 565-0871, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Takeda
authors.affiliation: Division of Pathogenesis and Control of Oral Diseases, Graduate School of Dentistry, Osaka University, 565-0871, Japan.
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Kogo
authors.affiliation: Laboratory of Neurogenesis and CNS Repair, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsuyama
authors.affiliation: Group of Neurobiology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. Electronic address: inagaki@sahs.med.osaka-u.ac.jp.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Inagaki
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002470:Cell Survival; D002540:Cerebral Cortex / Q000473:pathology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009836:Oligodendroglia / Q000473:pathology*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*
chemical_list: C103150:Sema4d protein, mouse; D039961:Semaphorins
keywords: Injury; Ischemia/reperfusion; Oligodendrocyte; Repair; Semaphorin