title: Selective CDK inhibitors: promising candidates for future clinical traumatic brain injury trials.
abstract: Traumatic brain injury induces secondary injury that contributes to neuroinflammation, neuronal loss, and neurological dysfunction. One important injury mechanism is cell cycle activation which causes neuronal apoptosis and glial activation. The neuroprotective effects of both non-selective (Flavopiridol) and selective (Roscovitine and CR-8) cyclin-dependent kinase inhibitors have been shown across multiple experimental traumatic brain injury models and species. Cyclin-dependent kinaseinhibitors, administered as a single systemic dose up to 24 hours after traumatic brain injury, provide strong neuroprotection-reducing neuronal cell death, neuroinflammation and neurological dysfunction. Given their effectiveness and long therapeutic window, cyclin-dependent kinase inhibitors appear to be promising candidates for clinical traumatic brain injury trials.
authors.affiliation: Department of Anesthesiology, Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Shruti V
authors.initials: SV
authors.lastname: Kabadi
authors.affiliation: Department of Anesthesiology, Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Alan I
authors.initials: AI
authors.lastname: Faden
keywords: CR-8; Roscovitine; behavior; cell cycle inhibition; lateral fluid percussion; microglial activation; neurodegeneration