Diazepam Inhibits Post-Traumatic Neurogenesis and Blocks Aberrant Dendritic Development

Journal of Neurotrauma
Laura E VillasanaEric Schnell

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 whethe...Continue Reading

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Brain Injury & Trauma

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