Annexin A1 as Neuroprotective Determinant for Blood-Brain Barrier Integrity in Neonatal Hypoxic-Ischemic Encephalopathy.

Autor: Gussenhoven R; Department of Pediatrics, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands. r.gussenhoven@maastrichtuniversity.nl.; School for Mental Health and Neuroscience (MHeNs), Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands. r.gussenhoven@maastrichtuniversity.nl., Klein L; Department of Pediatrics, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands. luise.klein@maastrichtuniversity.nl.; School for Mental Health and Neuroscience (MHeNs), Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands. luise.klein@maastrichtuniversity.nl., Ophelders DRMG; Department of Pediatrics, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands. d.ophelders@maastrichtuniversity.nl.; School of Oncology and Developmental Biology (GROW), Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands. d.ophelders@maastrichtuniversity.nl., Habets DHJ; School of Oncology and Developmental Biology (GROW), Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands. denise.habets@maastrichtuniversity.nl.; Department of Obstetrics and Gynecology, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands. denise.habets@maastrichtuniversity.nl., Giebel B; Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany. bernd.giebel@uk-essen.de., Kramer BW; Department of Pediatrics, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands. b.kramer@maastrichtuniversity.nl.; School for Mental Health and Neuroscience (MHeNs), Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands. b.kramer@maastrichtuniversity.nl.; School of Oncology and Developmental Biology (GROW), Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands. b.kramer@maastrichtuniversity.nl., Schurgers LJ; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands. l.schurgers@maastrichtuniversity.nl., Reutelingsperger CPM; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands. c.reutelingsperger@maastrichtuniversity.nl., Wolfs TGAM; Department of Pediatrics, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands. tim.wolfs@maastrichtuniversity.nl.; School of Oncology and Developmental Biology (GROW), Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands. tim.wolfs@maastrichtuniversity.nl.; Department of Biomedical Engineering (BMT), School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands. tim.wolfs@maastrichtuniversity.nl.
Jazyk: angličtina
Zdroj: Journal of clinical medicine [J Clin Med] 2019 Jan 24; Vol. 8 (2). Date of Electronic Publication: 2019 Jan 24.
DOI: 10.3390/jcm8020137
Abstrakt: Blood-brain barrier (BBB) disruption is associated with hypoxia-ischemia (HI) induced brain injury and life-long neurological pathologies. Treatment options are limited. Recently, we found that mesenchymal stem/stromal cell derived extracellular vesicles (MSC-EVs) protected the brain in ovine fetuses exposed to HI. We hypothesized that Annexin A1 (ANXA1), present in MSC-EVs, contributed to their therapeutic potential by targeting the ANXA1/Formyl peptide receptor (FPR), thereby preventing loss of the BBB integrity. Cerebral ANXA1 expression and leakage of albumin into the fetal ovine brain parenchyma after HI were analyzed by immunohistochemistry. For mechanistic insights, barrier integrity of primary fetal endothelial cells was assessed after oxygen-glucose deprivation (OGD) followed by treatment with MSC-EVs or human recombinant ANXA1 in the presence or absence of FPR inhibitors. Our study revealed that BBB integrity was compromised after HI which was improved by MSC-EVs containing ANXA1. Treatment with these MSC-EVs or ANXA1 improved BBB integrity after OGD, an effect abolished by FPR inhibitors. Furthermore, endogenous ANXA1 was depleted within 24 h after induction of HI in cerebovasculature and ependyma and upregulated 72 h after HI in microglia. Targeting ANXA1/FPR with ANXA1 in the immature brain has great potential in preventing BBB loss and concomitant brain injury following HI.
Databáze: MEDLINE
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