EphB3 signaling induces cortical endothelial cell death and disrupts the blood-brain barrier after traumatic brain injury article

Poincyane Assis-Nascimento, Yanina Tsenkina, Daniel J Liebl

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Damage to the cerebrovascular network is a major contributor to dysfunction in patients suffering from traumatic brain injury (TBI). Vessels are composed of lumen-forming endothelial cells that associate closely with both glial and neuronal units to establish a functional blood-brain barrier (BBB). Under normal physiological conditions, these vascular units play important roles in central nervous system (CNS) homeostasis by delivering oxygen and nutrients while filtering out molecules and cells that could be harmful; however, after TBI this system is disrupted. Here, we describe a novel role for a class of receptors, called dependence receptors, in regulating vessel stability and BBB integrity after CCI injury in mice. Specifically, we identified that EphB3 receptors function as a pro-Apoptotic dependence receptor in endothelial cells (ECs) that contributes to increased BBB damage after CCI injury. In the absence of EphB3, we observed increased endothelial cell survival, reduced BBB permeability and enhanced interactions of astrocyte-EC membranes. Interestingly, the brain's response to CCI injury is to reduce EphB3 levels and its ligand ephrinB3; however, the degree and timing of those reductions limit the protective response of the CNS. We conclude that EphB3 is a negative regulator of cell survival and BBB integrity that undermine tissue repair, and represents a protective therapeutic target for TBI patients.

Original languageEnglish (US)
Article number7
JournalCell Death and Disease
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Blood-Brain Barrier
Cell Death
Endothelial Cells
EphB3 Receptor
Cell Survival
Wounds and Injuries
Central Nervous System
Neuroglia
Astrocytes
Blood Vessels
Permeability
Homeostasis
Cell Membrane
Traumatic Brain Injury
Oxygen
Ligands
Food
Brain
Therapeutics

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

EphB3 signaling induces cortical endothelial cell death and disrupts the blood-brain barrier after traumatic brain injury article. / Assis-Nascimento, Poincyane; Tsenkina, Yanina; Liebl, Daniel J.

In: Cell Death and Disease, Vol. 9, No. 1, 7, 01.01.2018.

Research output: Contribution to journalArticle

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