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

Arina Riabinska, Marietta Zille, Menderes Yusuf Terzi, Ryan Cordell, Melina Nieminen-Kelhä, Jan Klohs, Ana Luisa Piña (Korresp. Autor*in)

Veröffentlichungen: Beitrag in FachzeitschriftArtikelPeer Reviewed

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.

OriginalspracheEnglisch
Seiten (von - bis)751-764
Seitenumfang14
FachzeitschriftCellular and Molecular Neurobiology
Jahrgang40
Ausgabenummer5
DOIs
PublikationsstatusVeröffentlicht - 1 Juli 2020
Extern publiziertJa

ÖFOS 2012

  • 106025 Neurobiologie
  • 301206 Pharmakologie
  • 301402 Neurobiologie

Zitationsweisen