Diazepam Inhibits Post-Traumatic Neurogenesis and Blocks Aberrant Dendritic Development

Laura Villasana, Austin Peters, Raluca McCallum, Chang Liu, Eric Schnell

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Traumatic brain injury (TBI) triggers a robust increase in neurogenesis within the dentate gyrus of the hippocampus, but these new neurons undergo aberrant maturation and dendritic outgrowth. Because gamma-aminobutyric acid (GABA)A receptors (GABAARs) modulate dendritic outgrowth during constitutive neurogenesis and GABAAR-modulating sedatives are often administered to human patients after TBI, we investigated whether the benzodiazepine, diazepam (DZP), alters post-injury hippocampal neurogenesis. We used a controlled cortical impact (CCI) model of TBI in adult mice, and administered DZP or vehicle continuously for 1 week after injury via osmotic pump. Although DZP did not affect the neurogenesis rate in control mice, it almost completely prevented the TBI-induced increase in hippocampal neurogenesis as well as the aberrant dendritic growth of neurons born after TBI. DZP did not reduce cortical injury, reactive gliosis, or cell proliferation early after injury, but decreased c-Fos activation in the dentate gyrus at both early and late time-points after TBI, suggesting an association between neuronal activity and post-injury neurogenesis. Because DZP blocks post-injury neurogenesis, further studies are warranted to assess whether benzodiazepines alter cognitive recovery or the development of complications after TBI.

Original languageEnglish (US)
Pages (from-to)2454-2467
Number of pages14
JournalJournal of neurotrauma
Volume36
Issue number16
DOIs
StatePublished - Aug 15 2019

Keywords

  • controlled cortical impact
  • diazepam
  • models of injury
  • neurogenesis
  • regeneration
  • traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

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