Endogenous Neural Stem/Progenitor Cells Stabilize the Cortical Microenvironment after Traumatic Brain Injury

Kirsty J. Dixon, Michelle H. Theus, Claudiu M. Nelersa, Jose Mier, Lissette G. Travieso, Tzong Shiue Yu, Steven G. Kernie, Daniel J Liebl

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Abstract Although a myriad of pathological responses contribute to traumatic brain injury (TBI), cerebral dysfunction has been closely linked to cell death mechanisms. A number of therapeutic strategies have been studied in an attempt to minimize or ameliorate tissue damage; however, few studies have evaluated the inherent protective capacity of the brain. Endogenous neural stem/progenitor cells (NSPCs) reside in distinct brain regions and have been shown to respond to tissue damage by migrating to regions of injury. Until now, it remained unknown whether these cells have the capacity to promote endogenous repair. We ablated NSPCs in the subventricular zone to examine their contribution to the injury microenvironment after controlled cortical impact (CCI) injury. Studies were performed in transgenic mice expressing the herpes simplex virus thymidine kinase gene under the control of the nestin<sup>δ</sup> promoter exposed to CCI injury. Two weeks after CCI injury, mice deficient in NSPCs had reduced neuronal survival in the perilesional cortex and fewer Iba-1-positive and glial fibrillary acidic protein-positive glial cells but increased glial hypertrophy at the injury site. These findings suggest that the presence of NSPCs play a supportive role in the cortex to promote neuronal survival and glial cell expansion after TBI injury, which corresponds with improvements in motor function. We conclude that enhancing this endogenous response may have acute protective roles after TBI.

Original languageEnglish (US)
Pages (from-to)753-764
Number of pages12
JournalJournal of Neurotrauma
Volume32
Issue number11
DOIs
StatePublished - Jun 1 2015

Fingerprint

Neural Stem Cells
Stem Cells
Wounds and Injuries
Neuroglia
Nestin
Thymidine Kinase
Lateral Ventricles
Glial Fibrillary Acidic Protein
Brain
Simplexvirus
Traumatic Brain Injury
Hypertrophy
Transgenic Mice
Cell Death
Genes

Keywords

  • Gliosis
  • Neural stem/progenitor cell ablation
  • Neurogenesis
  • Neuronal survival
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Endogenous Neural Stem/Progenitor Cells Stabilize the Cortical Microenvironment after Traumatic Brain Injury. / Dixon, Kirsty J.; Theus, Michelle H.; Nelersa, Claudiu M.; Mier, Jose; Travieso, Lissette G.; Yu, Tzong Shiue; Kernie, Steven G.; Liebl, Daniel J.

In: Journal of Neurotrauma, Vol. 32, No. 11, 01.06.2015, p. 753-764.

Research output: Contribution to journalArticle

Dixon, Kirsty J. ; Theus, Michelle H. ; Nelersa, Claudiu M. ; Mier, Jose ; Travieso, Lissette G. ; Yu, Tzong Shiue ; Kernie, Steven G. ; Liebl, Daniel J. / Endogenous Neural Stem/Progenitor Cells Stabilize the Cortical Microenvironment after Traumatic Brain Injury. In: Journal of Neurotrauma. 2015 ; Vol. 32, No. 11. pp. 753-764.
@article{e2190813a0d048e6990e77a80a523ef0,
title = "Endogenous Neural Stem/Progenitor Cells Stabilize the Cortical Microenvironment after Traumatic Brain Injury",
abstract = "Abstract Although a myriad of pathological responses contribute to traumatic brain injury (TBI), cerebral dysfunction has been closely linked to cell death mechanisms. A number of therapeutic strategies have been studied in an attempt to minimize or ameliorate tissue damage; however, few studies have evaluated the inherent protective capacity of the brain. Endogenous neural stem/progenitor cells (NSPCs) reside in distinct brain regions and have been shown to respond to tissue damage by migrating to regions of injury. Until now, it remained unknown whether these cells have the capacity to promote endogenous repair. We ablated NSPCs in the subventricular zone to examine their contribution to the injury microenvironment after controlled cortical impact (CCI) injury. Studies were performed in transgenic mice expressing the herpes simplex virus thymidine kinase gene under the control of the nestinδ promoter exposed to CCI injury. Two weeks after CCI injury, mice deficient in NSPCs had reduced neuronal survival in the perilesional cortex and fewer Iba-1-positive and glial fibrillary acidic protein-positive glial cells but increased glial hypertrophy at the injury site. These findings suggest that the presence of NSPCs play a supportive role in the cortex to promote neuronal survival and glial cell expansion after TBI injury, which corresponds with improvements in motor function. We conclude that enhancing this endogenous response may have acute protective roles after TBI.",
keywords = "Gliosis, Neural stem/progenitor cell ablation, Neurogenesis, Neuronal survival, Traumatic brain injury",
author = "Dixon, {Kirsty J.} and Theus, {Michelle H.} and Nelersa, {Claudiu M.} and Jose Mier and Travieso, {Lissette G.} and Yu, {Tzong Shiue} and Kernie, {Steven G.} and Liebl, {Daniel J}",
year = "2015",
month = "6",
day = "1",
doi = "10.1089/neu.2014.3390",
language = "English (US)",
volume = "32",
pages = "753--764",
journal = "Journal of Neurotrauma",
issn = "0897-7151",
publisher = "Mary Ann Liebert Inc.",
number = "11",

}

TY - JOUR

T1 - Endogenous Neural Stem/Progenitor Cells Stabilize the Cortical Microenvironment after Traumatic Brain Injury

AU - Dixon, Kirsty J.

AU - Theus, Michelle H.

AU - Nelersa, Claudiu M.

AU - Mier, Jose

AU - Travieso, Lissette G.

AU - Yu, Tzong Shiue

AU - Kernie, Steven G.

AU - Liebl, Daniel J

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Abstract Although a myriad of pathological responses contribute to traumatic brain injury (TBI), cerebral dysfunction has been closely linked to cell death mechanisms. A number of therapeutic strategies have been studied in an attempt to minimize or ameliorate tissue damage; however, few studies have evaluated the inherent protective capacity of the brain. Endogenous neural stem/progenitor cells (NSPCs) reside in distinct brain regions and have been shown to respond to tissue damage by migrating to regions of injury. Until now, it remained unknown whether these cells have the capacity to promote endogenous repair. We ablated NSPCs in the subventricular zone to examine their contribution to the injury microenvironment after controlled cortical impact (CCI) injury. Studies were performed in transgenic mice expressing the herpes simplex virus thymidine kinase gene under the control of the nestinδ promoter exposed to CCI injury. Two weeks after CCI injury, mice deficient in NSPCs had reduced neuronal survival in the perilesional cortex and fewer Iba-1-positive and glial fibrillary acidic protein-positive glial cells but increased glial hypertrophy at the injury site. These findings suggest that the presence of NSPCs play a supportive role in the cortex to promote neuronal survival and glial cell expansion after TBI injury, which corresponds with improvements in motor function. We conclude that enhancing this endogenous response may have acute protective roles after TBI.

AB - Abstract Although a myriad of pathological responses contribute to traumatic brain injury (TBI), cerebral dysfunction has been closely linked to cell death mechanisms. A number of therapeutic strategies have been studied in an attempt to minimize or ameliorate tissue damage; however, few studies have evaluated the inherent protective capacity of the brain. Endogenous neural stem/progenitor cells (NSPCs) reside in distinct brain regions and have been shown to respond to tissue damage by migrating to regions of injury. Until now, it remained unknown whether these cells have the capacity to promote endogenous repair. We ablated NSPCs in the subventricular zone to examine their contribution to the injury microenvironment after controlled cortical impact (CCI) injury. Studies were performed in transgenic mice expressing the herpes simplex virus thymidine kinase gene under the control of the nestinδ promoter exposed to CCI injury. Two weeks after CCI injury, mice deficient in NSPCs had reduced neuronal survival in the perilesional cortex and fewer Iba-1-positive and glial fibrillary acidic protein-positive glial cells but increased glial hypertrophy at the injury site. These findings suggest that the presence of NSPCs play a supportive role in the cortex to promote neuronal survival and glial cell expansion after TBI injury, which corresponds with improvements in motor function. We conclude that enhancing this endogenous response may have acute protective roles after TBI.

KW - Gliosis

KW - Neural stem/progenitor cell ablation

KW - Neurogenesis

KW - Neuronal survival

KW - Traumatic brain injury

UR - http://www.scopus.com/inward/record.url?scp=84930331340&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930331340&partnerID=8YFLogxK

U2 - 10.1089/neu.2014.3390

DO - 10.1089/neu.2014.3390

M3 - Article

C2 - 25290253

AN - SCOPUS:84930331340

VL - 32

SP - 753

EP - 764

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

SN - 0897-7151

IS - 11

ER -