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Vitamin D3 supplementation reduces subsequent brain injury and inflammation associated with ischemic stroke


Evans, MA and Kim, HA and Ling, YH and Uong, S and Vinh, A and De Silva, TM and Arumugam, TV and Clarkson, AN and Zosky, GR and Drummond, GR and Broughton, BRS and Sobey, CG, Vitamin D3 supplementation reduces subsequent brain injury and inflammation associated with ischemic stroke, Neuromolecular Medicine, 20, (1) pp. 147-159. ISSN 1535-1084 (2018) [Refereed Article]


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Copyright 2018 The Authors Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1007/s12017-018-8484-z


Acute inflammation can exacerbate brain injury after ischemic stroke. Beyond its well-characterized role in calcium metabolism, it is becoming increasingly appreciated that the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25-VitD3), has potent immunomodulatory properties. Here, we aimed to determine whether 1,25-VitD3 supplementation could reduce subsequent brain injury and associated inflammation after ischemic stroke. Male C57Bl6 mice were randomly assigned to be administered either 1,25-VitD3 (100 ng/kg/day) or vehicle i.p. for 5 day prior to stroke. Stroke was induced via middle cerebral artery occlusion for 1 h followed by 23 h reperfusion. At 24 h post-stroke, we assessed infarct volume, functional deficit, expression of inflammatory mediators and numbers of infiltrating immune cells. Supplementation with 1,25-VitD3 reduced infarct volume by 50% compared to vehicle. Expression of pro-inflammatory mediators IL-6, IL-1β, IL-23a, TGF-β and NADPH oxidase-2 was reduced in brains of mice that received 1,25-VitD3 versus vehicle. Brain expression of the T regulatory cell marker, Foxp3, was higher in mice supplemented with 1,25-VitD3 versus vehicle, while expression of the transcription factor, ROR-γ, was decreased, suggestive of a reduced Th17/γδ T cell response. Immunohistochemistry indicated that similar numbers of neutrophils and T cells were present in the ischemic hemispheres of 1,25-VitD3- and vehicle-supplemented mice. At this early time point, there were also no differences in the impairment of motor function. These data indicate that prior administration of exogenous vitamin D, even to vitamin D-replete mice, can attenuate infarct development and exert acute anti-inflammatory actions in the ischemic and reperfused brain.

Item Details

Item Type:Refereed Article
Keywords:stroke, vitamin D, inflammation, middle cerebral artery occlusion, mouse
Research Division:Biomedical and Clinical Sciences
Research Group:Cardiovascular medicine and haematology
Research Field:Cardiology (incl. cardiovascular diseases)
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Zosky, GR (Professor Graeme Zosky)
ID Code:125245
Year Published:2018
Funding Support:National Health and Medical Research Council (1042235)
Web of Science® Times Cited:40
Deposited By:Medicine
Deposited On:2018-04-10
Last Modified:2022-08-25
Downloads:132 View Download Statistics

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