Acute astrocytic and neuronal regulation of glutamatergic protein expression following blast

Regulation of glutamate through glutamate-glutamine cycling is critical for mediating nervous system plasticity. Blast-induced traumatic brain injury (bTBI) has been linked to glutamate-dependent excitotoxicity, which may be potentiating chronic disorders such as post-traumatic epilepsy. The purpose of this study was to measure changes in the expression of astrocytic and neuronal proteins responsible for glutamatergic regulation at 4-, 12-, and 24 h in the cortex and hippocampus following single blast exposure in a rat model for bTBI. Animals were exposed to a blast with magnitudes ranging from 16 to 20 psi using an Advanced Blast Simulator, and western blotting was performed to compare changes in protein expression between blast and sham groups. Glial fibrillary acidic protein (GFAP) was increased at 24 h, consistent with astrocyte reactivity, yet no other proteins showed significant changes in expression at acute time points following blast (GS, GLT-1, GluN1, GluN2A, GluN2B). Therefore, these glutamate regulators likely do not play a major role in contributing to acute excitotoxicity or glial reactivity when analyzed by whole brain region. Investigation of substructural and subregional effects in future studies, particularly within the hippocampus (e.g., dentate gyrus, CA1, CA2, CA3), may reveal localized changes in expression and/or NMDAR subunit composition capable of potentiating bTBI molecular cascades. Nevertheless, alternative regulators are likely to demonstrate greater sensitivity as acute therapeutic targets contributing to bTBI pathophysiology following single blast exposure.