Abstract 20: Vitamin D Deficiency Exacerbates Ischemic Cell Loss and Sensory Motor Dysfunction in an Experimental Stroke Model.
Vitamin D deficiency is widespread and considered a risk factor for cardiovascular disease and events such as stroke, and low Vitamin D (VD) levels are predictive for stroke and more fatal strokes in humans. VD’s ability to act as a selective endocrine and immunomodulator suggests a role for this hormone in reducing stroke-induced inflammation in the brain. However, the specific contribution of Vitamin D deficiency to stroke is not clear since it occurs with other co-morbid conditions, such as type 2 diabetes and obesity, which are also risk factors for cerebrovascular disease. To directly assess the impact of VD deficiency on stroke severity, adult female rats were fed control or VD deficient (VDD) diet for 6 weeks. The VDD diet reduced circulating VD levels to 25% of controls (p<0.05). Control and VDD groups were then subject to ischemic stroke by vasoconstriction of the Middle Cerebral Artery (MCA) by endothelin-1. Both groups displayed cortical and striatal infarction, however, infarct volumes were significantly larger in the VDD group in both the cortex (20%) and striatum (50%), when measured 5d post stroke. Furthermore, sensory motor function was more severely impaired in the VDD group, as measured by the tape test and the vibrissae evoked forelimb placement task (p<0.05). In the ischemic brain, IGF-1, which is a neuroprotective peptide hormone, is routinely elevated and the elevation was attenuated in the VDD groups (p<0.05). Additionally, VDD significantly reduced IL-1α, IL-1β, IL-2, IL-4, IFN-γ, and IL-10 expression in ischemic brain tissue, but elevated ischemia-induced IL-6. IL-6 was positively correlated with infarct volume (r2=.83 cortex, r2=.90 striatum) (p<.05). IL-6 promotes development and expansion of the Th17 cohort, whose cytokines secretions are a key factor in blood brain barrier disruption after stroke. These data support the hypothesis that VD deficiency independently modulates stroke severity by disrupting the expression of normally neuroprotective compounds (IGF-1) and elevating cytotoxic proteins (IL-6) in the ischemic brain. Supported by NIH AG027684 and AG028303 to FS.
- © 2012 by American Heart Association, Inc.