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Overexpression of Mfsd2a attenuates blood brain barrier dysfunction via Cav-1/Keap-1/Nrf-2/HO-1 pathway in a rat model of surgical brain injury

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dc.contributor.authorOcak, Umut
dc.contributor.authorSherchan, Prativa
dc.contributor.authorGamdzyk, Marcin
dc.contributor.authorTang, Jiping
dc.contributor.authorZhang, John H.
dc.contributor.buuauthorOcak, Pınar Eser
dc.contributor.departmentTıp Fakültesi
dc.contributor.orcid0000-0003-0132-9927
dc.contributor.researcheridAAI-2073-2021
dc.contributor.scopusid57200969645
dc.date.accessioned2022-12-19T06:55:21Z
dc.date.available2022-12-19T06:55:21Z
dc.date.issued2020-01-16
dc.description.abstractIntroduction: Disruption of the blood brain barrier (BBB) and subsequent cerebral edema formation is one of the major adverse effects of brain surgery, leading to postoperative neurological dysfunction. Recently, Mfsd2a has been shown to have a crucial role for the maintenance of BBB functions. In this study, we aimed to evaluate the role of Mfsd2a on BBB disruption following surgical brain injury (SBI) in rats. Materials and methods: Rats were subjected to SBI by partial resection of the right frontal lobe. To evaluate the effect of Mfsd2a on BBB permeability and neurobehavior outcome following SBI, Mfsd2a was either over-expressed or downregulated in the brain by administering Mfsd2a CRISPR activation or knockout plasmids, respectively. The potential mechanism of Mfsd2a-mediated BBB protection through the cav-1/Nrf-2/HO-1 signaling pathway was evaluated. Results: Mfsd2a levels were significantly decreased while cav-1, Nrf-2 and HO-1 levels were increased in the right frontal perisurgical area following SBI. When overexpressed, Mfsd2a attenuated brain edema and abolished neurologic impairment caused by SBI while downregulation of Mfsd2a expression further deteriorated BBB functions and worsened neurologic performance following SBI. The beneficial effect of Mfsd2a overexpression on BBB functions was associated with diminished expression of cav-1, increased Keap-1/Nrf-2 dissociation and further augmented levels of Nrf-2 and HO-1 in the right frontal perisurgical area, leading to enhanced levels of tight junction proteins following SBI. The BBB protective effect of Mfsd2a was blocked by selective inhibitors of Nrf-2 and HO-1. Conclusions: Mfsd2a attenuates BBB disruption through cav-1/Nrf-2/HO-1 signaling pathway in rats subjected to experimental SBI.
dc.description.sponsorshipNational Institutes of Health
dc.description.sponsorshipNational Institute of Neurological Disorders and Stroke
dc.identifier.citationOcak, P. E. vd. (2020). "Overexpression of Mfsd2a attenuates blood brain barrier dysfunction via Cav-1/Keap-1/Nrf-2/HO-1 pathway in a rat model of surgical brain injury". Experimental Neurology, 326.
dc.identifier.issn0014-4886
dc.identifier.pubmed31954682
dc.identifier.scopus2-s2.0-85078106610
dc.identifier.urihttps://doi.org/10.1016/j.expneurol.2020.113203
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S0014488620300340
dc.identifier.urihttp://hdl.handle.net/11452/29945
dc.identifier.volume326
dc.identifier.wos000515193000010
dc.indexed.scopusScopus
dc.indexed.wosSCIE
dc.language.isoen
dc.publisherAcademic Press Inc Elsevier Science
dc.relation.collaborationYurt içi
dc.relation.collaborationYurt dışı
dc.relation.collaborationSanayi
dc.relation.journalExperimental Neurology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectBlood brain barrier
dc.subjectBrain edema
dc.subjectCav-1
dc.subjectCaveolae
dc.subjectMfsd2a
dc.subjectSurgical brain injury
dc.subjectExpression
dc.subjectCaveolae
dc.subjectDamage
dc.subjectPathophysiology
dc.subjectComplications
dc.subjectPermeability
dc.subjectInhibition
dc.subjectClaudin-5
dc.subjectProtects
dc.subjectOccludin
dc.subjectNeurosciences & neurology
dc.subject.emtreeCaveolin 1
dc.subject.emtreeHeme oxygenase 1
dc.subject.emtreeKelch like ECH associated protein 1
dc.subject.emtreePeptides and proteins
dc.subject.emtreeProtein Mfsd2a
dc.subject.emtreeTranscription factor Nrf2
dc.subject.emtreeUnclassified drug
dc.subject.emtreeHeme oxygenase
dc.subject.emtreeHmox1 protein, rat
dc.subject.emtreeKEAP1 protein, rat
dc.subject.emtreeKelch like ECH associated protein 1
dc.subject.emtreeNfe2l2 protein, rat
dc.subject.emtreeTranscription factor Nrf2
dc.subject.emtreeAdult
dc.subject.emtreeAnimal experiment
dc.subject.emtreeAnimal model
dc.subject.emtreeAnimal tissue
dc.subject.emtreeArticle
dc.subject.emtreeBlood brain barrier
dc.subject.emtreeBrain injury
dc.subject.emtreeControlled study
dc.subject.emtreeMale
dc.subject.emtreeNonhuman
dc.subject.emtreePriority journal
dc.subject.emtreeProtein expression
dc.subject.emtreeRat
dc.subject.emtreeRat model
dc.subject.emtreeSignal transduction
dc.subject.emtreeAnimal
dc.subject.emtreeAnimal behavior
dc.subject.emtreeBody water
dc.subject.emtreeBrain injury
dc.subject.emtreeFrontal lobe
dc.subject.emtreeGene therapy
dc.subject.emtreeGenetics
dc.subject.emtreeInjury
dc.subject.emtreeMetabolism
dc.subject.emtreePathophysiology
dc.subject.emtreeSprague Dawley rat
dc.subject.emtreeTreatment outcome
dc.subject.meshAnimals
dc.subject.meshBehavior, animal
dc.subject.meshBlood-brain barrier
dc.subject.meshBody water
dc.subject.meshBrain injuries
dc.subject.meshCaveolin 1
dc.subject.meshFrontal lobe
dc.subject.meshGenetic therapy
dc.subject.meshHeme oxygenase (decyclizing)
dc.subject.meshKelch-like ECH-associated protein 1
dc.subject.meshMale
dc.subject.meshNF-E2-related factor 2
dc.subject.meshRats
dc.subject.meshRats, sprague-dawley
dc.subject.meshSignal transduction
dc.subject.meshTreatment outcome
dc.subject.scopusCaveolin 1; Animals; Endothelial Nitric Oxide Synthase
dc.subject.wosNeurosciences
dc.titleOverexpression of Mfsd2a attenuates blood brain barrier dysfunction via Cav-1/Keap-1/Nrf-2/HO-1 pathway in a rat model of surgical brain injury
dc.typeArticle
dc.wos.quartileQ2
dc.wos.quartileQ2
dspace.entity.typePublication
local.contributor.departmentTıp Fakültesi
local.indexed.atPubMed
local.indexed.atWOS
local.indexed.atScopus

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