Time Course Study of GFRα-1 Expression in an Animal Model of Stroke

Previous studies have shown that intracerebral administration of glial cell line-derived neurotrophic factor (GDNF) reduces ischemia-mediated cerebral infarction. The biological effects of GDNF are mediated by GDNF-family receptor α-1 (GFRα-1) and c-Ret. In this study, we examined the levels of expression of GFRα-1 and c-Ret in a rat model of stroke. Adult Sprague–Dawley rats were anesthetized with chloral hydrate. The right middle cerebral artery was ligated at its distal branch for 90 min. Animals were sacrificed at 0, 6, 12, and 24 h after reperfusion and levels of expression of GFRα-1 and c-Ret mRNA were determined by in situ hybridization histochemistry. We found that GFRα-1 mRNA was up-regulated in CA3, dentate gyrus (DG), cortex, and striatum. The peak of up-regulation in DG was 6 h after reperfusion. GFRα-1 mRNA levels in CA3 were gradually up-regulated over the 24-h reperfusion period. In cortex, GFRα-1 mRNA was up-regulated at all time points; however, the peak of up-regulation was observed at 0 and 24 h after reperfusion. In striatum, an initial up-regulation of GFRα-1 was found at 0 h after ischemia. In striatum, up-regulation of c-Ret mRNA was detected as early as 0 h after reperfusion. A gradual increase was found at 6, 12, and 24 h after reperfusion. In conclusion, our results indicate that there are both regional and temporal differences in up-regulation of GFRα-1 and c-Ret after ischemia. Since GDNF is neuroprotective, up-regulation of GFRα-1 and c-Ret could enhance the responsiveness to GDNF and reduce neuronal damage. The selective up-regulation of GFRα-1 and c-Ret in different brain areas suggests that there may be regional differences in GDNF-induced neuroprotection in stroke.