A combined treatment with 1α,25-dihydroxy-vitamin D 3 and 17β-estradiol reduces the expression of heat shock protein-32 (HSP-32) following cerebral cortical ischemia

Abstract

1α,25-(OH) 2-vitamin D 3 (1,25-D 3) and 17β-estradiol are both known to act neuroprotectively in certain experimental in vitro and in vivo settings and it has been noted that both steroids lead to an upregulation of certain neurotrophic factors. Here, we studied the effects of 1α,25-(OH) 2-vitamin D 3 or 17β-estradiol or their combined application on heat shock protein-32 (HSP-32) distribution after focal cortical ischemia using the well established photothrombosis model. Heat shock protein-32 is a well-established marker of the cerebral oxidative stress response and contributes to neuroprotection by metabolising cytotoxic free heme to carbon monoxide, iron and biliverdin. Photothrombotically lesioned rats were injected i.p. 1 h after injury with either 1 μg 1α,25-(OH) 2-vitamin D 3/kg or 7 μg 17β-estradiol/kg or a combination of both steroids. Groups of non-lesioned steroid-treated rats and lesioned, solvent-treated rats served as controls. In contrast to non-lesioned rats, in lesioned animals a significant increase in heat shock protein-32 expression occurred which was slightly, but non-significantly altered in the groups treated either with 1α,25-(OH) 2-vitamin D 3 or 17β-estradiol alone when compared to the solvent-treated control group. Only the combined treatment with 1α,25-(OH) 2-vitamin D 3 and 17β-estradiol resulted in a significant reduction of glial heat shock protein-32 immunoreactivity within the lesion-remote cortical areas supplied by the affected middle cerebral artery (MCA), indicating that both steroids act synergistically in a protective manner.