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EphrinB3 blocks EphB3 dependence receptor functions to prevent cell death following traumatic brain injury
Journal article   Open access   Peer reviewed

EphrinB3 blocks EphB3 dependence receptor functions to prevent cell death following traumatic brain injury

M H Theus, J Ricard, S J Glass, L G Travieso and D J Liebl
Cell death & disease, v 5(5), pp e1207-e1207
01 May 2014
DOI: https://doi.org/10.1038/cddis.2014.165
PMID: 24810043
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1038/cddis.2014.165View
Published, Version of Record (VoR) Open

Abstract

Animals Apoptosis - drug effects Brain - drug effects Brain - enzymology Brain - pathology Brain - physiopathology Brain Injuries - drug therapy Brain Injuries - enzymology Brain Injuries - genetics Brain Injuries - pathology Brain Injuries - physiopathology Cell Line, Tumor Cytoprotection Disease Models, Animal Ephrin-B3 - administration & dosage Ephrin-B3 - deficiency Ephrin-B3 - genetics Ephrin-B3 - metabolism HEK293 Cells Humans Infusions, Intraventricular Male Mice Mice, Knockout Motor Activity - drug effects Nerve Degeneration Neurons - drug effects Neurons - enzymology Neurons - pathology Neuroprotective Agents - administration & dosage Receptor, EphB3 - deficiency Receptor, EphB3 - genetics Receptor, EphB3 - metabolism Recovery of Function Rotarod Performance Test Time Factors Transfection
Eph receptor tyrosine kinases and their membrane-bound ligands, ephrins, have a variety of roles in the developing and adult central nervous system that require direct cell-cell interactions; including regulating axon path finding, cell proliferation, migration and synaptic plasticity. Recently, we identified a novel pro-survival role for ephrins in the adult subventricular zone, where ephrinB3 blocks Eph-mediated cell death during adult neurogenesis. Here, we examined whether EphB3 mediates cell death in the adult forebrain following traumatic brain injury and whether ephrinB3 infusion could limit this effect. We show that EphB3 co-labels with microtubule-associated protein 2-positive neurons in the adult cortex and is closely associated with ephrinB3 ligand, which is reduced following controlled cortical impact (CCI) injury. In the complete absence of EphB3 (EphB3(-/-)), we observed reduced terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL), and functional improvements in motor deficits after CCI injury as compared with wild-type and ephrinB3(-/-) mice. We also demonstrated that EphB3 exhibits dependence receptor characteristics as it is cleaved by caspases and induces cell death, which is not observed in the presence of ephrinB3. Following trauma, infusion of pre-clustered ephrinB3-Fc molecules (eB3-Fc) into the contralateral ventricle reduced cortical infarct volume and TUNEL staining in the cortex, dentate gyrus and CA3 hippocampus of wild-type and ephrinB3(-/-) mice, but not EphB3(-/-) mice. Similarly, application of eB3-Fc improved motor functions after CCI injury. We conclude that EphB3 mediates cell death in the adult cortex through a novel dependence receptor-mediated cell death mechanism in the injured adult cortex and is attenuated following ephrinB3 stimulation.

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29 citations in Web of Science
30 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Cell Biology
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