1α,25-Dihydroxyvitamin D3 treatment does not alter neuronal cyclooxygenase-2 expression in the cerebral cortex after stroke

Abstract

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.

Vitamin D3 and Ischemic Stroke: A Narrative Review

“…In that study 1,25(OH)2D3 (4 μg/kg body weight) did not prolong ischemia-induced HO-1 expression but reduced reactive gliosis in the lesioned brain region. Using the same model of stroke, Oermann et al (2006) revealed that the post-ischemic neuronal cyclooxygenase-2 (COX-2) upregulation did not contribute to the neuroprotective mechanism of calcitriol [ 116 ]. Balden et al (2012) observed in female rats that an 8 week vitamin D deficient (VDD) diet, which reduced circulating vitamin D levels to 22% of that observed in rats fed control chow, worsened MCAO-evoked brain injury and dysregulated the post-stroke inflammation.…”