1alpha,25-dihydroxy-vitamin D3 in combination with 17beta-estradiol lowers the cortical expression of heat shock protein-27 following experimentally induced focal cortical ischemia in rats

1alpha,25-(OH)(2)-vitamin-D(3) (1,25-D(3)) and 17beta-estradiol are both known to act neuroprotective in certain experimental in vitro and in vivo settings. We studied the effects of 1,25-D(3) or 17beta-estradiol or their combined application on heat shock protein-27 (HSP-27) distribution after focal cortical ischemia using the photothrombosis model. HSP-27 is a well-established marker of the cerebral oxidative stress response and a potent inhibitor of apoptosis. Lesioned rats were injected i.p. one hour after injury with either 1 microg 1,25-D(3)/kg or 7 microg 17beta-estradiol/kg or a combination of both steroids. Groups of non-lesioned steroid-treated rats and lesioned, solvent-treated rats served as controls. Treatment with both steroids did not affect the size of the lesion. In addition, 17beta-estradiol resulted in significant reduction of HSP-27 induction, whereas the combination of 1,25-D(3)+17beta-estradiol resulted in a highly significant reduction of HSP-27 within the infracted cerebral cortex, indicating that both steroids act synergistically in a protective manner.