Calcitriol Pretreatment Attenuates Glutamate Neurotoxicity by Regulating NMDAR and CYP46A1 Gene Expression in Rats Subjected to Transient Middle Cerebral Artery Occlusion

Abstract

Abstract Although the neuroprotective effects of calcitriol have been demonstrated in a variety of neurological diseases, such as stroke, the precise molecular mechanism has yet to be determined. This study aimed to investigate the possible role of calcitriol as a neuroprotective agent via CYP46A1 and glutamate receptors in a middle cerebral artery occlusion (MCAO) animal model. The MCAO technique was performed on adult male Wistar rats to induce focal cerebral ischemia for 1 hour followed by 23 hours of reperfusion. Calcitriol was given for 7 days prior to stroke induction. Sensorimotor functional tests were done 24 hours after ischemia/reperfusion, and infarct volume was estimated by tetrazolium chloride staining of brain sections. Gene expression of NR2A, NR2B, NR3B, and CYP46A1 was evaluated by RT-PCR followed by western blotting for NR3B protein. Our data revealed that calcitriol pretreatment reduced lesion volume and improved ischemic neurobehavioral parameters. Calcitriol therapy altered the expression of glutamate receptor and CYP46A1 genes. A possible molecular mechanism of calcitriol to reduce the severity and complications of ischemia may be through alterations of glutamate receptor and CYP46A1 gene expression.