Beneficial compaction of spinal cord lesion by migrating astrocytes through glycogen synthase kinase-3 inhibition.
Bottom Line: This treatment resulted in accelerated migration of reactive astrocytes to sequester inflammatory cells that spared myelinated fibres and significantly promoted functional recovery.A variety of in vitro and in vivo experiments further suggested that GSK-3 inhibition stimulated astrocyte migration by decreasing adhesive activity via reduced surface expression of β1-integrin.Our results reveal a novel benefit of GSK-3 inhibition for SCI and suggest that the stimulation of astrocyte migration is a feasible therapeutic strategy for traumatic injury in the central nervous system.
Affiliation: Department of Physiology, Keio University School of Medicine, Tokyo, Japan.Show MeSH
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Mentions: Next, the in vivo effects of Ro3303544 after SCI were examined. To focus on the compaction of inflammatory cells by reactive astrocytes, the protocol consisted of intraperitoneal administration of Ro3303544 for only the first 5 days after thoracic contusive SCI in mice (Fig 3A). This is in contrast to a previous report in which Dill et al (2008) administered SB415286 for 3–4 weeks after SCI and reported increased axonal growth and improved functional recovery. Axonal growth is a delayed event that commences after the inflammatory reaction has subsided, while the compaction of inflammatory cells by reactive astrocytes occurs during the sub-acute phase of SCI, namely the first 2 weeks after injury in mice (Okada et al, 2006).
Affiliation: Department of Physiology, Keio University School of Medicine, Tokyo, Japan.