| First Author | Reinhart KM | Year | 2018 |
| Journal | Exp Neurol | Volume | 305 |
| Pages | 121-128 | PubMed ID | 29653188 |
| Mgi Jnum | J:268150 | Mgi Id | MGI:6271076 |
| Doi | 10.1016/j.expneurol.2018.04.007 | Citation | Reinhart KM, et al. (2018) Ketamine reduces deleterious consequences of spreading depolarizations. Exp Neurol 305:121-128 |
| abstractText | Recent work has implicated spreading depolarization (SD) as a key contributor the progression of acute brain injuries, however development of interventions selectively targeting SD 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 30muM) did not prevent SD, but significantly reduced neuronal Ca(2+) loading and the duration of associated extracellular potential shifts. Recovery of postsynaptic potentials after SD was also significantly accelerated. When SD was evoked on a background of mild metabolic compromise, neuronal recovery was substantially impaired. Under compromised conditions, the same concentrations of ketamine reduced ionic and metabolic loading during SD, sufficient to preserve functional recovery after repetitive SDs. These results suggest that lower concentrations of ketamine could be utilized to prevent damaging consequences of SD, while not blocking them outright and thereby preserving potentially protective effects of SD. |
