Effects of stromal cell-derived factor 1_ delivered at different phases of transient focal ischemia in rats-

Authors
J. Yoo, J.-J. Seo, J.-H. Eom, D.-Y. Hwang.

Lab
CHA University, College of Natural Science, Department of Biomedical Science, Seoul, Korea.

Journal
Neuroscience

Abstract
Endogenous stromal cell-derived factor 1_ (SDF1_) has been implicated in postischemic tissue repair, suggesting SDF1_ 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 SDF1_ when it is delivered at different phases of stroke. In our study, adenovirus expressing SDF1_ gene (AV-SDF1_) 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-SDF1_ was injected 3 days before ischemia, which might be the result of SDF1_-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-SDF1_-injected brain, which contributed to further amelioration at later time points (delayed response). On the contrary, when AV-SDF1_ 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 SDF1_ varied considerably depending on when SDF1_ overexpression was initiated; initiating SDF1_ overexpression before ischemia exerted both immediate and delayed beneficial effects, whereas initiating overexpression in the subacute phase exerted only a delayed response.

BIOSEB Instruments Used:
Aron Test or Four Plates Test (LE830),Rotarod (BX-ROD)