1Alpha,25-dihydroxyvitamin D3 treatment does not alter neuronal cyclooxygenase-2 expression in the cerebral cortex after stroke.
The inducible prostaglandin synthase, cyclooxygenase-2, is upregulated in response to cerebral ischemia and contributes to potentiation of oxidative injury. Cyclooxygenase-2 expression is regulated by retinoic acid receptors, which form heterodimers with vitamin D receptors and vitamin D. In addition, vitamin D has been reported to have neuroprotective qualities. The aim of this study was to examine whether the biologically active vitamin D3-metabolite 1alpha,25-dihydroxyvitamin D3 (1,25-D3), influences the expression of inducible cyclooxygenase-2 in photothrombotically lesioned brain or is part of an independent neuroprotective mechanism. We compared groups of nonlesioned control rats and infarcted animals, which were treated with either 1,25-D3 or solvent at different times postlesion. In control animals, cyclooxygenase-2 immunoreactivity was readily evident in almost all cortical neurons of layers II/III as well as in a few pyramidal cells in layer V. Following photothrombotic infarction of the right cortical hindlimb area, there was a significant, but transient, increase in cyclooxygenase-2 labeling which was restricted to neurons of the injured hemisphere in both 1,25- D3-treated and solvent-treated rats. Highest levels of cyclooxygenase-2 immunoreactivity were seen at 12 and 24 h postlesion, followed by a gradual decrease at later time points. However, no significant differences were detected between 1,25-D3-treated and solvent-treated lesioned rats, indicating that postischemic neuronal cyclooxygenase-2 upregulation is not influenced by 1,25-D3. It is concluded that the neuroprotective effect of 1,25-D3 does not depend on modulations of neuronal COX-2 expression caused by postlesional hyperexcitation.
Oermann
Evelyn
E
C.&O. Vogt Institute for Brain Research, University of Düsseldorf, 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 / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D007124:Immunoenzyme Techniques; D020767:Intracranial Thrombosis / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D051546:Cyclooxygenase 2; D002117:Calcitriol