Spreading depolarizations mediate excitotoxicity in the development of acute cortical lesions.

Spreading depolarizations mediate excitotoxicity in the development of acute cortical lesions.
Exp Neurol. 2015 Mar 24;
Authors: Hinzman JM, DiNapoli VA, Mahoney EJ, Gerhardt GA, Hartings JA
Abstract
Spreading depolarizations (SD) are mass depolarizations of neurons and astrocytes that occur spontaneously in acute brain injury and mediate time-dependent lesion growth. Glutamate excitotoxicity has also been extensively studied as a mechanism of neuronal injury, although its relevance to in vivo pathology remains unclear. Here we hypothesized that excitotoxicity in acute lesion development occurs only as a consequence of SD. Using glutamate-sensitive microelectrodes, we found that SD induced by KCl in normal rat cortex elicits increases in extracellular glutamate (11.6±1.3μM) that are synchronous with the onset, sustainment, and resolution of the extracellular direct-current shift of SD. Inhibition of glutamate uptake with d,l-threo-β-benzyloxyaspartate (TBOA, 0.5 and 1mM) significantly prolonged the duration of the direct-current shift (148% and 426%, respectively) and the glutamate increase (167% and 374%, respectively) in a dose-dependent manner (P<0.05). These prolonged events produced significant cortical lesions as indicated by Fluoro-Jade staining (P<0.05), while no lesions were observed after SD in control conditions or after cortical injection of 1mM glutamate (extracellular increase: 243±50.8μM) or 0.5mM TBOA (glut...

Source: Experimental Neurology - March 24, 2015 Category: Neurology Authors: Hinzman JM, DiNapoli VA, Mahoney EJ, Gerhardt GA, Hartings JA Tags: Exp Neurol Source Type: research