Anti-inflammatory effects of active Vitamin D hormone on extracranial vessels after subarachnoid hemorrhage in a murine model

Subarachnoid hemorrhage (SAH) causes systemic inflammation and endothelial dysfunction, contributing to cerebral vasospasm and poor outcomes. While Vitamin D hormone (1,25-dihydroxy cholecalciferol, calcitriol, 1,25-VitD) has known vasoprotective and anti-inflammatory effects, its role in extracranial vascular response and neurological recovery after SAH remains unclear. Adult male C57BL/6N mice received daily intraperitoneal injections of 1,25-VitD (100 ng/kg) for five days prior to experimental SAH induction via cisterna magna blood injection.

Vascular inflammation was quantified in carotid, femoral, and basilar arteries using RT-qPCR. Endothelial function was assessed ex vivo by wire myography. Neurological deficits and systemic responses were evaluated using the modified Neurological Severity Score (mNSS) and body weight change.

VDR knockout lines were used to dissect cell-specific mechanisms. SAH triggered robust upregulation of TNF-α, IL-6, VCAM-1, and ICAM-1 across extracranial arteries. 1,25-VitD pretreatment significantly suppressed this inflammatory response (p