Hypoxic-ischemic brain injury activates early hippocampal stem/progenitor cells to replace vulnerable neuroblasts

Darryl K. Miles, Steven G. Kernie

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Although the phenomenon of ongoing neurogenesis in the hippocampus is well described, it remains unclear what relevance this has in terms of brain self-repair following injury. In a highly regulated developmental program, new neurons are added to the inner granular cell layer of the dentate gyrus (DG) where slowly dividing radial glial-like type 1 neural stem/progenitors (NSPs) give rise to rapidly proliferating type 2 neural progenitors which undergo selection and maturation into functional neurons. The induction of these early hippocampal progenitors after injury may represent an endogenous mechanism for brain recovery and remodeling. To determine what role early hippocampal progenitors play in remodeling following injury, we utilized a model of hypoxic-ischemic injury on young transgenic mice that express green fluorescent protein (GFP) specifically in neural progenitors. We demonstrate that this injury selectively activates programmed cell death in committed but immature neuroblasts, which is followed by proliferation of both early type 1 and later type 2 progenitors. This subsequently leads to newly generated neurons becoming stably incorporated into the DG.

Original languageEnglish (US)
Pages (from-to)793-806
Number of pages14
JournalHippocampus
Volume18
Issue number8
DOIs
StatePublished - Sep 1 2008

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Keywords

  • Apoptosis
  • DG
  • Development
  • Neural stem cell
  • Subgranular zone

ASJC Scopus subject areas

  • Cognitive Neuroscience

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