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.
Subject(s)
Chemokine CXCL12/genetics , Genetic Therapy/methods , Ischemic Attack, Transient/therapy , Adenoviridae , Animals , Blotting, Western , Cell Differentiation/physiology , Cell Movement/physiology , Genetic Vectors , Immunohistochemistry , In Situ Nick-End Labeling , Ischemic Attack, Transient/pathology , Male , Nerve Regeneration/physiology , Neurogenesis/physiology , Rats , Rats, Sprague-Dawley , Recovery of Function/physiology , Transduction, GeneticABSTRACT
Two acid-inducible genes, aniC and aciK, that require anaerobiosis and tyrosine for expression were identified as orf326a encoding a potential amino acid/polyamine antiporter and hyaB encoding hydrogenase I, respectively. Cyclic AMP (cAMP) receptor protein, cAMP, and TyrR, regulator of aromatic amino acid metabolism, were strong positive regulators of both genes.
