Effects of 1alpha,25 dihydroxyvitamin D3 on the expression of HO-1 and GFAP in glial cells of the photothrombotically lesioned cerebral cortex.
In ischemic cerebral injuries a cascade of degenerative mechanisms, all participating in the development of oxidative stress, influence the condition of the tissue. The survival of viable tissue affected by secondary injury largely depends on the balance between endogenous protective mechanisms and the ongoing degenerative processes. The inducible enzyme, heme oxygenase-1 metabolizes and thus detoxifies free heme to the powerful endogenous antioxidants biliverdin and bilirubin therefore enhancing neuroprotection. The secosteroid 1alpha,25-dihydroxyvitamin D3 (1,25-D3) is a modulator of the immune system and also exhibits a strong potential for neuroprotection as recently shown in the MCAO model of cerebral ischemia. We studied the effects of 1,25-D3 treatment on heme oxygenase-1 expression following focal cortical ischemia elicited by photothrombosis. Postlesional treatment with 1,25-D3 (4 microg/kg body weight) resulted in a transient, but significant upregulation of glial heme oxygenase-1 immunoreactivity concomitant with a reduction in glial fibrillary acidic protein immunoreactivity in remote cortical regions affected by a secondary spread of injury, whereas the size of the lesion's core remained unaffected. 1,25-D3 did not produce a temporal shift or extension of injury-related heme oxygenase-1 responses, indicating that 1,25-D3 did not prolong ischemia-related heme oxygenase-1 expression. In contrast to glial heme oxygenase-1 upregulation, glial fibrillary acidic protein, a sensitive marker for reactive gliosis, was significantly reduced. These findings support an additional protective action of 1,25-D3 at the cellular level in regions affected by secondary injury-related responses.
Oermann
Evelyn
E
C.&O. Vogt Institute for Brain Research, Heinrich Heine University of Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany. oermann@uni-duesseldorf.de
Bidmon
Hans-J
HJ
Witte
Otto-W
OW
Zilles
Karl
K
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D020767:Intracranial Thrombosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012395:Rose Bengal
D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D012395:Rose Bengal; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D002117:Calcitriol