Absence of Sema4D improves oligodendrocyte recovery after cerebral ischemia/reperfusion injury in mice. (July 2016)

• Record Type: Journal Article
• Authors: Wada, Takenobu; Sawano, Toshinori; Tanaka, Takashi; Furuyama, Tatsuo; Fukumoto, Moe; Yamaguchi, Wataru; Saino, Orie; Takeda, Yuichi; Kogo, Mikihiko; Matsuyama, Tomohiro; Inagaki, Shinobu
• Is Part Of: Neuroscience research. Volume 108(2016:Jul.)
• Page Start: 6
• Page End: 11
• Publication Date: 2016-07
• Subjects: Ischemia/reperfusion -- Injury -- Repair -- Semaphorin -- Oligodendrocyte; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2015.12.016
• Languages: English
• ISSNs: 0168-0102

Abstract

Highlights: The effect of Sema4D-deficiency on oligodendrocyte was studied in mice. Direct ligation of the middle cerebral artery and reperfusion were employed. The peri-infarct area showed a transient decrease of oligodendrocytes. Sema4D KOs showed enhanced oligodendrocyte recovery compared to wild-type mice. Sema4D-deficiency enhanced proliferation and survival of oligodendrocytes. 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.