title: EphrinB3 restricts endogenous neural stem cell migration after traumatic brain injury.
abstract: Traumatic brain injury (TBI) leads to a series of pathological events that can have profound influences on motor, sensory and cognitive functions. Conversely, TBI can also stimulate neural stem/progenitor cell proliferation leading to increased numbers of neuroblasts migrating outside their restrictive neurogenic zone to areas of damage in support of tissue integrity. Unfortunately, the factors that regulate migration are poorly understood. Here, we examine whether ephrinB3 functions to restrict neuroblasts from migrating outside the subventricular zone (SVZ) and rostral migratory stream (RMS). We have previously shown that ephrinB3 is expressed in tissues surrounding these regions, including the overlying corpus callosum (CC), and is reduced after controlled cortical impact (CCI) injury. Our current study takes advantage of ephrinB3 knockout mice to examine the influences of ephrinB3 on neuroblast migration into CC and cortex tissues after CCI injury. Both injury and/or ephrinB3 deficiency led to increased neuroblast numbers and enhanced migration outside the SVZ/RMS zones. Application of soluble ephrinB3-Fc molecules reduced neuroblast migration into the CC after injury and limited neuroblast chain migration in cultured SVZ explants. Our findings suggest that ephrinB3 expression in tissues surrounding neurogenic regions functions to restrict neuroblast migration outside the RMS by limiting chain migration.
authors: The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami, 1095 NW 14th Terrace, Miami, FL 33136, USA; Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, 1101 East Marshall Street, Richmond, VA 23298, USA. Electronic address: Kirsty.dixon@vcuhealth.org.
authors: Kirsty J
authors: KJ
authors: Dixon
authors: The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami, 1095 NW 14th Terrace, Miami, FL 33136, USA. Electronic address: jmier2@med.miami.edu.
authors: Jose
authors: J
authors: Mier
authors: The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami, 1095 NW 14th Terrace, Miami, FL 33136, USA. Electronic address: sgajavel@med.miami.edu.
authors: Shyam
authors: S
authors: Gajavelli
authors: Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: alisa@unimelb.edu.au.
authors: Alisa
authors: A
authors: Turbic
authors: The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami, 1095 NW 14th Terrace, Miami, FL 33136, USA. Electronic address: rbullock@med.miami.edu.
authors: Ross
authors: R
authors: Bullock
authors: Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: turnley@unimelb.edu.au.
authors: Ann M
authors: AM
authors: Turnley
authors: The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami, 1095 NW 14th Terrace, Miami, FL 33136, USA. Electronic address: dliebl@med.miami.edu.
authors: Daniel J
authors: DJ
authors: Liebl
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D036389:Ephrin-B3 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology*
chemical_list: D036389:Ephrin-B3
keywords: EphrinB3; Migration; Neuroblast; Traumatic brain injury