Next Article in Journal
Breast Cancer Systemic Treatments and Upper Limb Lymphedema: A Risk-Assessment Platform Encompassing Tumor-Specific Pathological Features Reveals the Potential Role of Trastuzumab
Next Article in Special Issue
Factors Associated with Parents’ Adherence to Different Types of Exercises in Home Programs for Children with Disabilities
Previous Article in Journal
Prediction of the Outcome of Cochlear Implantation in the Patients with Congenital Cytomegalovirus Infection based on Magnetic Resonance Imaging Characteristics
Article Menu
Issue 2 (February) cover image

Export Article

Open AccessArticle

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

1
Department of Pediatrics, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands
2
School for Mental Health and Neuroscience (MHeNs), Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands
3
School of Oncology and Developmental Biology (GROW), Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands
4
Department of Obstetrics and Gynecology, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands
5
Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
6
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands
7
Department of Biomedical Engineering (BMT), School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands
*
Authors to whom correspondence should be addressed.
Shared first authorship.
J. Clin. Med. 2019, 8(2), 137; https://doi.org/10.3390/jcm8020137
Received: 23 November 2018 / Revised: 8 January 2019 / Accepted: 20 January 2019 / Published: 24 January 2019
  |  
PDF [3710 KB, uploaded 24 January 2019]
  |     |  

Abstract

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. View Full-Text
Keywords: Annexin A1/Formyl peptide receptor axis; blood-brain barrier; mesenchymal stem cell-derived extracellular vesicles; neonatal hypoxia-ischemia; therapy Annexin A1/Formyl peptide receptor axis; blood-brain barrier; mesenchymal stem cell-derived extracellular vesicles; neonatal hypoxia-ischemia; therapy
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Gussenhoven, R.; Klein, L.; Ophelders, D.R.M.G.; Habets, D.H.J.; Giebel, B.; Kramer, B.W.; Schurgers, L.J.; Reutelingsperger, C.P.M.; Wolfs, T.G.A.M. Annexin A1 as Neuroprotective Determinant for Blood-Brain Barrier Integrity in Neonatal Hypoxic-Ischemic Encephalopathy. J. Clin. Med. 2019, 8, 137.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
J. Clin. Med. EISSN 2077-0383 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top