Vitamin D Prevents Spatial Learning and Memory Disturbance and Vascular Remodelling in the Hippocampus After Transient Global Cerebral Ischemia

Introduction: The hippocampus is susceptible to ischemic injury, which can lead to a decline in the ability to use spatial learning and memory. It is established that vitamin D has neuroprotective properties. This study aims to determine the impact of vitamin D on the deterioration of spatial learning and memory performance and hippocampal vascular characteristics following transient global cerebral ischemia (tGCI). Materials and methods: Four groups of male Wistar rats were created: sham-operated (C1), tGCI (C2), tGCI with vitamin D injection 0,125 µg/kg/ day (D1) and 0,5 µg/kg/day (D2) i.p. for 10 days. The induction of tGCI was achieved using the bilateral common carotid artery occlusion (BCCAO) technique. Spatial learning and memory function were assessed using the Morris Water Maze (MWM) test. Results: During the MWM learning phase, the C2 group took the longest time to reach the platform. Compared to the C2 group, the number of platform crossings in the MWM test was higher in the D1 and D2 groups. A greater lumen/wall area ratio and thinner wall thickness were seen in the D1 and D2 groups during intra-hippocampal artery measurement. The D1 and D2 groups had lower levels of preproEndothelin-1 (ppET-1) and Endothelin-1 type A receptor (ETAR) mRNA expression. Endothelial nitric oxide synthase (eNOS) mRNA expression was higher in the D1 and D2 groups. Conclusion: In summary, our findings suggest that vitamin D enhances spatial learning and memory and may protect the hippocampus by modulating vascular remodelling, decreasing ppET-1 and ETAR levels, and increasing eNOS production. © 2025 Universiti Putra Malaysia Press. All rights reserved.