TY - JOUR
T1 - Diazepam inhibits post-traumatic neurogenesis and blocks aberrant dendritic development
AU - Villasana, Laura E.
AU - Peters, Austin
AU - McCallum, Raluca
AU - Liu, Chang
AU - Schnell, Eric
N1 - Publisher Copyright:
© Copyright 2019, Mary Ann Liebert, Inc., publishers 2019.
PY - 2019/8/15
Y1 - 2019/8/15
N2 - 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.
AB - 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.
KW - controlled cortical impact
KW - diazepam
KW - models of injury
KW - neurogenesis
KW - regeneration
KW - traumatic brain injury
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U2 - 10.1089/neu.2018.6162
DO - 10.1089/neu.2018.6162
M3 - Article
C2 - 30794026
AN - SCOPUS:85071069068
SN - 0897-7151
VL - 36
SP - 2454
EP - 2467
JO - Journal of neurotrauma
JF - Journal of neurotrauma
IS - 16
ER -