Universität zu Köln

Riabinska, Arina, Zille, Marietta ORCID: 0000-0002-0609-8956, Terzi, Menderes Yusuf, Cordell, Ryan, Nieminen-Kelhae, Melina, Klohs, Jan ORCID: 0000-0003-4065-2807 and Pina, Ana Luisa (2020). Pigment Epithelium-Derived Factor Improves Paracellular Blood-Brain Barrier Integrity in the Normal and Ischemic Mouse Brain. Cell. Mol. Neurobiol., 40 (5). S. 751 - 765. NEW YORK: SPRINGER/PLENUM PUBLISHERS. ISSN 1573-6830

Full text not available from this repository.

Abstract

Pigment 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Riabinska, Arina UNSPECIFIED UNSPECIFIED UNSPECIFIED Zille, Marietta UNSPECIFIED orcid.org/0000-0002-0609-8956 UNSPECIFIED Terzi, Menderes Yusuf UNSPECIFIED UNSPECIFIED UNSPECIFIED Cordell, Ryan UNSPECIFIED UNSPECIFIED UNSPECIFIED Nieminen-Kelhae, Melina UNSPECIFIED UNSPECIFIED UNSPECIFIED Klohs, Jan UNSPECIFIED orcid.org/0000-0003-4065-2807 UNSPECIFIED Pina, Ana Luisa UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-124096
DOI:	10.1007/s10571-019-00770-9
Journal or Publication Title:	Cell. Mol. Neurobiol.
Volume:	40
Number:	5
Page Range:	S. 751 - 765
Date:	2020
Publisher:	SPRINGER/PLENUM PUBLISHERS
Place of Publication:	NEW YORK
ISSN:	1573-6830
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL-GROWTH-FACTOR; MIDDLE CEREBRAL-ARTERY; CEREBELLAR GRANULE CELLS; FACTOR PEDF; QUANTITATIVE-EVALUATION; VASCULAR-PERMEABILITY; OXIDATIVE STRESS; FACTOR VEGF; EXPRESSION; ANGIOGENESIS Multiple languages Cell Biology; Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12409