Pigment Epithelium-Derived Factor Improves Paracellular Blood-Brain Barrier Integrity in the Normal and Ischemic Mouse Brain

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dc.authoridNieminen-Kelha, Melina/0000-0002-7577-8058
dc.authoridKlohs, Jan/0000-0003-4065-2807
dc.authoridTerzi, Menderes Yusuf/0000-0001-8478-0451
dc.authoridZille, Marietta/0000-0002-0609-8956
dc.contributor.authorRiabinska, Arina
dc.contributor.authorZille, Marietta
dc.contributor.authorTerzi, Menderes Yusuf
dc.contributor.authorCordell, Ryan
dc.contributor.authorNieminen-Kelhae, Melina
dc.contributor.authorKlohs, Jan
dc.contributor.authorPina, Ana Luisa
dc.date.accessioned2024-09-18T20:04:36Z
dc.date.available2024-09-18T20:04:36Z
dc.date.issued2020
dc.departmentHatay Mustafa Kemal Üniversitesien_US
dc.description.abstractPigment epithelium-derived factor (PEDF) is a neurotrophic factor with neuroprotective, antiangiogenic, and antipermeability effects. In the brain, blood-brain barrier (BBB) function is essential for homeostasis. Its impairment plays a crucial role in the pathophysiology of many neurological diseases, including ischemic stroke. We investigated (a) whether PEDF counteracted vascular endothelial growth factor (VEGF)-induced BBB disruption in the mouse brain, (b) the time course and route of BBB permeability and the dynamics of PEDF expression after cerebral ischemia, and (c) whether intraventricular infusion of PEDF ameliorated brain ischemia by reducing BBB impairment. C57Bl6/N mice received intraparenchymal injections of CSF, VEGF, or a combination of VEGF and PEDF. PEDF increased paracellular but not transcellular BBB integrity as indicated by an increase in the tight junction protein claudin-5. In another group of mice undergoing 60-min middle cerebral artery occlusion (MCAO), transcellular BBB permeability (fibrinogen staining in the absence of a loss of claudin-5) increased as early as 6 h after reperfusion. PEDF immunofluorescence increased at 24 h, which paralleled with a decreased paracellular BBB permeability (claudin-5). PEDF after MCAO originated from the blood stream and endogenous pericytes. In the third experiment, the intraventricular infusion of PEDF decreased edema and cell death after MCAO, potentially mediated by the improvement of the paracellular route of BBB permeability (claudin-5) in the absence of an amelioration of Evans Blue extravasation. Together, our data suggest that PEDF improves BBB function after cerebral ischemia by affecting the paracellular but not the transcellular route. However, further quantitative data of the different routes of BBB permeability will be required to validate our findings.en_US
dc.description.sponsorshipDepartment of Neurosurgery; Charite Rahel Hirsch Habilitation Fellowship; Berlin-Brandenburg Center for Regenerative Therapies Flexible Funds [BCRTFF2008-17, BCRTFF2009-38]; Stiftung der Deutschen Wirtschaft (Foundation of German Business); Department of Experimental Neurologyen_US
dc.description.sponsorshipThis work was possible thanks to the financial support from the Departments of Neurosurgery and Experimental Neurology, by the Charite Rahel Hirsch Habilitation Fellowship and Berlin-Brandenburg Center for Regenerative Therapies Flexible Funds (No. BCRTFF2008-17 and BCRTFF2009-38) all granted to Dr. Ana-Luisa Pina. Marietta Zille was supported by a fellowship granted by the Stiftung der Deutschen Wirtschaft (Foundation of German Business).en_US
dc.identifier.doi10.1007/s10571-019-00770-9
dc.identifier.endpage764en_US
dc.identifier.issn0272-4340
dc.identifier.issn1573-6830
dc.identifier.issue5en_US
dc.identifier.pmid31858356en_US
dc.identifier.scopus2-s2.0-85077072629en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage751en_US
dc.identifier.urihttps://doi.org/10.1007/s10571-019-00770-9
dc.identifier.urihttps://hdl.handle.net/20.500.12483/8272
dc.identifier.volume40en_US
dc.identifier.wosWOS:000535521300001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringer/Plenum Publishersen_US
dc.relation.ispartofCellular and Molecular Neurobiologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectBlood-brain barrieren_US
dc.subjectCerebral ischemiaen_US
dc.subjectClaudin-5en_US
dc.subjectFibrinogenen_US
dc.subjectMCAOen_US
dc.subjectPigment epithelium-derived factoren_US
dc.titlePigment Epithelium-Derived Factor Improves Paracellular Blood-Brain Barrier Integrity in the Normal and Ischemic Mouse Brainen_US
dc.typeArticleen_US

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