Calcitriol provides neuroprotection against cerebral ischemia-reperfusion injury through activation of the SIRT1 pathway.

Ischemic stroke, caused by arterial blockages, is a major global cause of mortality and long-term disability. Current treatments primarily aim to restore cerebral blood flow through the use of anticoagulant therapy and thrombectomy. Recent research has explored vitamin D3, particularly its active form, calcitriol, as an adjunctive treatment due to its neuroprotective effects. However, the exact mechanisms by which calcitriol mitigates ischemia-induced brain injury remain unclear. This study investigated the therapeutic potential of calcitriol in ischemia/reperfusion (I/R) injury using a rat model. Male Wistar rats were subjected to 1 hour of ischemia followed by 72 hours of reperfusion to establish an I/R injury model. The rats then received calcitriol treatment for three days. Neurobehavioral deficits and cerebral infarct volume were evaluated 72 hours post-ischemia. Oxidative stress markers-including malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC)-were quantified. Additionally, RT-PCR was performed to assess mRNA expression levels of SIRT1 and PGC1-α. The study demonstrated that calcitriol administration significantly reduced cerebral infarct volume and improved neurological outcomes following I/R injury. Treatment with calcitriol effectively decreased oxidative stress markers, as evidenced by reduced MDA and NO levels, while simultaneously enhancing TAC. Notably, calcitriol treatment substantially upregulated mRNA expression of SIRT1 in ischemic brain tissue. Our results demonstrate that calcitriol exhibits neuroprotective effects against I/R injury. These benefits appear to be mediated through two key mechanisms: (1) attenuation of oxidative stress and (2) activation of the SIRT1/PGC1-α signaling pathway.