A combined treatment with 1alpha,25-dihydroxy-vitamin D3 and 17beta-estradiol reduces the expression of heat shock protein-32 (HSP-32) following cerebral cortical ischemia.
1alpha,25-(OH)(2)-vitamin D(3) (1,25-D(3)) and 17beta-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 1alpha,25-(OH)(2)-vitamin D(3) or 17beta-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. 1h after injury with either 1 microg 1alpha,25-(OH)(2)-vitamin 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. 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 1alpha,25-(OH)(2)-vitamin D(3) or 17beta-estradiol alone when compared to the solvent-treated control group. Only the combined treatment with 1alpha,25-(OH)(2)-vitamin D(3) and 17beta-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.
Losem-Heinrichs
Eva
E
C.&O. Vogt Institute of Brain Research, University St. 1, 40225 Düsseldorf, Germany.
Görg
Boris
B
Schleicher
Axel
A
Redecker
Christoph
C
Witte
Otto W
OW
Zilles
Karl
K
Bidmon
Hans-J
HJ
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing); D007150:Immunohistochemistry; D008297:Male; D010105:Oxygenases; D051381:Rats; D017208:Rats, Wistar
D006360:Heat-Shock Proteins; D004958:Estradiol; D010105:Oxygenases; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D002117:Calcitriol