Traumatic brain injury-induced hippocampal neurogenesis requires activation of early nestin-expressing progenitors

Tzong Shiue Yu, Gui Zhang, Daniel J Liebl, Steven G. Kernie

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

It is becoming increasingly clear that brain injuries from a variety of causes stimulate neurogenesis within the hippocampus. It remains unclear, however, how robust this response may be and what primary cell types are involved. Here, using a controlled cortical impact model of traumatic brain injury on a previously characterized transgenic mouse line that expresses enhanced green fluorescent protein (eGFP) under the control of the nestin promoter, we demonstrate that it is the earliest type-1 quiescent progenitor cells that are induced to proliferate and migrate outside the subgranular layer of the dentate gyrus. This type-1 cell activation occurs at the same time that we observe adjacent but more differentiated doublecortin-expressing progenitors (type-2 cells) being eliminated. Also, although type-2 cells remain intact in the contralateral (uninjured) dentate gyrus, the type-1 cells there are also activated and result in increased numbers of the doublecortin-expressing type-2 cells. In addition, we have generated a novel mouse transgenic that expresses a modified version of the herpes simplex virus thymidine kinase along with eGFP that allows for the visualization and inducible ablation of early dividing progenitors by exposing them to ganciclovir. Using this transgenic in the context of traumatic brain injury, we demonstrate that these early progenitors are required for injury-induced remodeling to occur. This work suggests that injury-induced hippocampal remodeling following brain injury likely requires sustained activation of quiescent early progenitors.

Original languageEnglish
Pages (from-to)12901-12912
Number of pages12
JournalJournal of Neuroscience
Volume28
Issue number48
DOIs
StatePublished - Nov 26 2008

Fingerprint

Nestin
Neurogenesis
Dentate Gyrus
Brain Injuries
Transgenic Mice
Stem Cells
Ganciclovir
Thymidine Kinase
Wounds and Injuries
Simplexvirus
Hippocampus
Traumatic Brain Injury

Keywords

  • Dentate gyrus
  • Hippocampus
  • Neurogenesis
  • Neuronal progenitor cell
  • Neuroprotection
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Traumatic brain injury-induced hippocampal neurogenesis requires activation of early nestin-expressing progenitors. / Yu, Tzong Shiue; Zhang, Gui; Liebl, Daniel J; Kernie, Steven G.

In: Journal of Neuroscience, Vol. 28, No. 48, 26.11.2008, p. 12901-12912.

Research output: Contribution to journalArticle

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