Ketamine improves neuronal recovery following spreading depolarization in peri ‐infarct tissues

We examined spreading depolarization (SD) waves in a mouse stroke model. SDs were initiated by focal potassium chloride application and propagated through a region of graded perfusion deficit created by distal middle cerebral artery (dMCA) occlusion. Longer lasting depolarizations (DC shifts measured from local field potential (LFP) electrodes) and neuronal Ca2+ transients (epifluorescence GCaMP imaging) occurred at locations with larger perfusion deficits (proximal to occlusion), as compared with remote recording sites (laser speckle contrast imaging (LSCI) of cerebral perfusion). Ketamine, at concentrations that did not abolish the propagation of SD, improved recovery from SD and reduced Ca2+ loading. These findings suggest that deleterious consequences of SD can be targeted in vivo, without requiring outright block of SD initiation and propagation. AbstractSpreading depolarization (SD) has emerged as an important contributor to the enlargement of acute brain injuries. We previously showed that the N-methyl-D-aspartate receptor antagonist ketamine was able to prevent deleterious consequences of SD in brain slices, under conditions of metabolic compromise. The current study aimed to extend these observations into an in vivo stroke model, to test whether gradients of metabolic capacity lead to differential accumulation of calcium (Ca2+) following SD. In addition, we tested whether ketamine protects vulnerable tissuewhile allowing SD to propagate through surrounding undamaged ...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research