Abstract Body:
Emerging research suggests that Vitamin D3 might help protect against brain damage caused by ischemic stroke, as a deficiency in Vitamin D3 can worsen the severity and outcomes of a stroke. To investigate this, we studied the impact of Vitamin D3 on maintaining the integrity of the blood-brain barrier (BBB) using a mouse model of stroke. The BBB is severely disrupted during all kinds of strokes, which can lead to further injury and functional deficits. We measured several biomarkers related to BBB disruption to see if Vitamin D3 treatment could protect the BBB after a stroke. Mice were randomly divided into two diet groups: one receiving a Vitamin D3-sufficient diet (VDHsuf) and the other a Vitamin D3-deficient diet (VDHdef). The VDHsuf group ate standard chow, while the VDHdef group consumed a diet lacking Vitamin D3 for 8 weeks. Both groups underwent middle cerebral artery occlusion (MCAO) surgery for 40 minutes followed by reperfusion for 72 h. We assessed BBB disruption by measuring even blue leakage, matrix metalloproteinase-9 (MMP-9/MMP-2) activity, and changes in tight junction (TJ) proteins. We also evaluated the expression of OPG, RANKL, osteopontin (OPN), and the Vitamin D receptor (VDR) in both diet groups. At the time of MCAO, mice on the Vitamin D3-deficient diet had low levels of Vitamin D3. After MCAO, Evans blue leakage, indicating more severe BBB injury, was significantly greater in the VDHdef group compared to the VDHsuf group. Additionally, the expression of MMP-9, GLUT1, VDR, OPG, and OPN increased, while TJ proteins occluding, claudin-5 and RANKL decreased in the VDHdef group. These findings suggest that Vitamin D3 deficiency can impair the BBB, potentially worsening stroke severity and its long-term effects.