PMID- 30618630 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240105 IS - 1662-5102 (Print) IS - 1662-5102 (Electronic) IS - 1662-5102 (Linking) VI - 12 DP - 2018 TI - 1, 25-D(3) Protects From Cerebral Ischemia by Maintaining BBB Permeability via PPAR-gamma Activation. PG - 480 LID - 10.3389/fncel.2018.00480 [doi] LID - 480 AB - The blood-brain barrier (BBB) is a physical and biochemical barrier that maintains cerebral homeostasis. BBB dysfunction in an ischemic stroke, results in brain injury and subsequent neurological impairment. The aim of this study was to determine the possible protective effects of 1, 25-dihydroxyvitamin D(3) [1, 25(OH)(2)D(3), 1, 25-D(3), vit D] on BBB dysfunction, at the early stages of an acute ischemic brain injury. We analyzed the effects of 1, 25-D(3) on BBB integrity in terms of histopathological changes, the neurological deficit, infarct size and the expression of brain derived neurotrophic factor (BDNF), in a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model. BBB permeability and the expression of permeability-related proteins in the brain were also evaluated by Evans blue (EB) staining and Western blotting respectively. To determine the possible mechanism underlying the role of 1, 25-D(3) in BBB maintenance, after MCAO/R, the rats were treated with the specific peroxisome proliferator-activated receptor gamma (PPARgamma) inhibitor GW9662. Supplementation with 1, 25-D(3) markedly improved the neurological scores of the rats, decreased the infarct volume, prevented neuronal deformation and upregulated the expression of the tight junction (TJ) and BDNF proteins in their brains. Furthermore, it activated PPARgamma but downregulated neuro-inflammatory cytokines such as nuclear factor kappa-B (NF-kappaB) and tumor necrosis factor-alpha (TNF-alpha), after MCAO/R. Taken together, 1, 25-D(3) protects against cerebral ischemia by maintaining BBB permeability, upregulating the level of BDNF and inhibiting PPARgamma-mediated neuro-inflammation. FAU - Guo, Ting AU - Guo T AD - Department of Neurology, Xuzhou Medical University, Xuzhou, China. FAU - Wang, Yanqiang AU - Wang Y AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. AD - Department of Neurology, The Affiliated Hospital of Weifang Medical University, Weifang, China. FAU - Guo, Yuanfang AU - Guo Y AD - Department of Respiratory Medicine, Ganyu District People's Hospital, Lianyungang, China. FAU - Wu, Shuguang AU - Wu S AD - Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. FAU - Chen, Weiwei AU - Chen W AD - Department of Neurology, The Central Hospital of Xuzhou, Xuzhou, China. FAU - Liu, Na AU - Liu N AD - Department of Neurology, Xuzhou Medical University, Xuzhou, China. FAU - Wang, Yu AU - Wang Y AD - Department of Neurology, Xuzhou Medical University, Xuzhou, China. FAU - Geng, Deqin AU - Geng D AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. LA - eng PT - Journal Article PT - Retracted Publication DEP - 20181217 PL - Switzerland TA - Front Cell Neurosci JT - Frontiers in cellular neuroscience JID - 101477935 RIN - Front Cell Neurosci. 2023 Dec 21;17:1355800. PMID: 38179206 PMC - PMC6304345 OTO - NOTNLM OT - 1 OT - 25-D3 OT - BBB permeability OT - BDNF OT - MCAO/R OT - NF-kappaB OT - PPARgamma OT - inflammation COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2019/01/09 06:00 MHDA- 2019/01/09 06:01 PMCR- 2018/01/01 CRDT- 2019/01/09 06:00 PHST- 2018/09/26 00:00 [received] PHST- 2018/11/23 00:00 [accepted] PHST- 2019/01/09 06:00 [entrez] PHST- 2019/01/09 06:00 [pubmed] PHST- 2019/01/09 06:01 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - 10.3389/fncel.2018.00480 [doi] PST - epublish SO - Front Cell Neurosci. 2018 Dec 17;12:480. doi: 10.3389/fncel.2018.00480. eCollection 2018.