Anti-inflammatory effects of active Vitamin D hormone on extracranial vessels after subarachnoid hemorrhage in a murine model
Abstract
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 < 0.05), preserved endothelial-dependent vasorelaxation (p < 0.01), and improved neurological scores and attenuated systemic weight loss (p < 0.05). Notably, the protective effects of 1,25-VitD were not observed in mice lacking VDR in LysM-positive myeloid or endothelial cells. 1,25-VitD pretreatment attenuates the systemic vascular dysfunction occurring after SAH. These findings identify VDR-dependent modulation of early vascular inflammation and endothelial dysfunction as a potential mechanism of 1,25-VitD-mediated vascular protection after experimental SAH. Whether these effects can be achieved by treatment initiated after SAH and translated into clinical benefit requires further investigation.
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BibTeX
@article{kashefiolasl2026antiinflammatory,
title = {{Anti-inflammatory effects of active Vitamin D hormone on extracranial vessels after subarachnoid hemorrhage in a murine model}},
author = {Sepide Kashefiolasl and Matthias S. Leisegang and Katrin Schroeder and Ralf P. Brandes},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-74821-9},
url = {https://www.nature.com/articles/s41598-026-74821-9},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Anti-inflammatory effects of active Vitamin D hormone on extracranial vessels after subarachnoid hemorrhage in a murine model
AU - Sepide Kashefiolasl
AU - Matthias S. Leisegang
AU - Katrin Schroeder
AU - Ralf P. Brandes
PY - 2026
DA - 2026/10/12
JO - Scientific Reports
DO - 10.1038/s41598-026-74821-9
UR - https://www.nature.com/articles/s41598-026-74821-9
AB - 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 < 0.05), preserved endothelial-dependent vasorelaxation (p < 0.01), and improved neurological scores and attenuated systemic weight loss (p < 0.05). Notably, the protective effects of 1,25-VitD were not observed in mice lacking VDR in LysM-positive myeloid or endothelial cells. 1,25-VitD pretreatment attenuates the systemic vascular dysfunction occurring after SAH. These findings identify VDR-dependent modulation of early vascular inflammation and endothelial dysfunction as a potential mechanism of 1,25-VitD-mediated vascular protection after experimental SAH. Whether these effects can be achieved by treatment initiated after SAH and translated into clinical benefit requires further investigation.
SN - 2045-2322
ER -