Vitamin D deficiency increases blood-brain barrier dysfunction after ischemic stroke in male rats.
Exp Neurol. 2018 Nov 28 ;312:63-71. Epub 2018 Nov 28. PMID: 30502340
Because vitamin D hormone deficiency (VDH) can worsen severity and outcome for ischemic stroke, we examined the role of VDH in maintaining blood-brain-barrier (BBB integrity) in a rat model of stroke. In most types of stroke, the BBB is markedly compromised, potentially leading to a cascade of injury processes and functional deficits, so we examined a number of biomarkers associated with BBB disruption to determine whether VDH deficiency would further compromise the BBB following a stroke. Male Wistar rats were randomly assigned to one of two diet cohorts, VDH-sufficient (VDH) and VDH. The VDHgroup was fed standard rat chow and the VDHgroup got a VDH-null version of the same diet for 8 weeks. Animals from both cohorts were subjected to transient middle cerebral artery occlusion (tMCAO) surgery, killed at 72 h post-stroke, and their brains evaluated for BBB permeability and injury severity using expression of immunoglobulin (IgG), matrix metalloproteinase-9 (MMP-9) activity and alteration of tight junction (TJ) proteins as markers of BBB disruption. We also evaluated modulation of glucose transporter-1 (GLUT1), osteopontin (OPN), β-catenin and vitamin D receptor (VDR) expression in VDHand VDHsubjects. At the time of MCAO, rats on the VDHdiet had circulating VDH levels one-fourth that of rats fed control chow. IgG extravasation after MCAO, indicating more severe BBB injury, was significantly higher in the MCAO+VDHthan the MCAO+VDHrats. Following MCAO, expression of MMP-9, GLUT1, VDR and OPN increased and the TJ proteins occludin and claudin-5 decreased significantly in the VDHcompared to the VDHgroup. We also observed significantly lower expression ofβ-catenin in the MCAO group of both VDHand VDHrats. Under these conditions, VDH deficiency itself can compromise the BBB. We think that low serum VDH levels are likely to complicate stroke severity and its chronic consequences.