Ketamine reduces deleterious consequences of spreading depolarizations.

Ketamine reduces deleterious consequences of spreading depolarizations.
Exp Neurol. 2018 Apr 10;:
Authors: Reinhart KM, William Shuttleworth C
Abstract
Recent work has implicated spreading depolarization (SD) as a key contributor the progression of acute brain injuries, however development of interventions selectively targeting SDs has lagged behind. Initial clinical intervention efforts have focused on observations that relatively high doses of the sedative agent ketamine can completely suppress SD. However blocking propagation of SD could theoretically prevent beneficial effects of SD in surrounding brain regions. Selective targeting of deleterious consequences of SD (rather than abolition) could be a useful adjunct approach, and be achieved with lower ketamine concentrations. We utilized a brain slice model to test whether deleterious consequences of SD could be prevented by ketamine, using concentrations that did not prevent the initiation and propagation of SD. Studies were conducted using murine brain slices, with focal KCl as an SD stimulus. Consequences of SD were assessed with electrophysiological and imaging measures of ionic and synaptic recovery. Under control conditions, ketamine (up to 30 μM) did not prevent SD, but significantly reduced the duration of neuronal Ca2+ loading, and the duration of associated extracellular potential shifts. Recovery of postsynaptic potentials after SD, was also significantly accelerated...

Source: Experimental Neurology - April 10, 2018 Category: Neurology Authors: Reinhart KM, William Shuttleworth C Tags: Exp Neurol Source Type: research