Phosphodiesterase-4 inhibition restored hippocampal long term potentiation after primary blast.

Phosphodiesterase-4 inhibition restored hippocampal long term potentiation after primary blast. Exp Neurol. 2017 Mar 30;: Authors: Vogel EW, Morales FN, Meaney DF, Bass CR, Morrison B Abstract Due to recent military conflicts and terrorist attacks, blast-induced traumatic brain injury (bTBI) presents a health concern for military and civilian personnel alike. Although secondary blast (penetrating injury) and tertiary blast (inertia-driven brain deformation) are known to be injurious, the effects of primary blast caused by the supersonic shock wave interacting with the skull and brain remain debated. Our group previously reported that in vitro primary blast exposure reduced long-term potentiation (LTP), the electrophysiological correlate of learning and memory, in rat organotypic hippocampal slice cultures (OHSCs) and that primary blast affects key proteins governing LTP. Recent studies have investigated phosphodiesterase-4 (PDE4) inhibition as a therapeutic strategy for reducing LTP deficits following inertia-driven TBI. We investigated the therapeutic potential of PDE4 inhibitors, specifically roflumilast, to ameliorate primary blast-induced deficits in LTP. We found that roflumilast at concentrations of 1nM or greater prevented deficits in neuronal plasticity measured 24h post-injury. We also observed a therapeutic window of at least 6h, but <23h. Additionally, we investigated molecular mechanisms that could elucidate this thera...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research