title: Effects of stromal cell-derived factor 1α delivered at different phases of transient focal ischemia in rats.
abstract: Endogenous stromal cell-derived factor 1α (SDF1α) has been implicated in postischemic tissue repair, suggesting SDF1α as a potential therapeutic molecule to treat stroke patients. In spite of its potential, no data are available regarding the short- and long-term effects of SDF1α when it is delivered at different phases of stroke. In our study, adenovirus expressing SDF1α gene (AV-SDF1α) was introduced into the boundary of the infarcted area either 3 days before or 1 week after ischemia, and behavioral performance was measured over 5 weeks. Immediate behavioral and structural amelioration was evident when AV-SDF1α was injected 3 days before ischemia, which might be the result of SDF1α-mediated neuroprotection as supported by the TUNEL staining and Western blot analysis of active caspase-3. In addition, increase in neurogenesis, neuroblast migration, and neural differentiation was also apparent in the AV-SDF1α-injected brain, which contributed to further amelioration at later time points ("delayed response"). On the contrary, when AV-SDF1α was introduced 1 week post-ischemia (in the subacute phase), significant behavioral recovery became apparent beginning 5 weeks after viral delivery. Taken together, the therapeutic efficacy of SDF1α varied considerably depending on when SDF1α overexpression was initiated; initiating SDF1α overexpression before ischemia exerted both immediate and delayed beneficial effects, whereas initiating overexpression in the subacute phase exerted only a delayed response.
authors.affiliation: Department of Biomedical Science, College of Natural Science, CHA University, Seoul, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Yoo
authors.forename: J-J
authors.initials: JJ
authors.lastname: Seo
authors.forename: J-H
authors.initials: JH
authors.lastname: Eom
authors.forename: D-Y
authors.initials: DY
authors.lastname: Hwang
mesh_terms: D000256:Adenoviridae; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D054377:Chemokine CXCL12 / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000628:therapy*; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D014161:Transduction, Genetic
chemical_list: D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse