Glutamate Receptor and Kynurenine Pathway Functioning in the Pathobiology of Gulf War Illness

ABSTRACT

This project has 2 aims: (i) examine the involvement in veterans with Gulf War Illness of a neural excitatory state as a consequence of impaired brain immune, neuron and glia functioning using biomarkers obtained from cerebrospinal fluid (CSF) in 1990-1991 Gulf War veterans with (n=46) and without (n=23) GWI, and (ii) examine involvement in veterans with GWI of a neural excitatory state defined as increased glutamatergic receptor functioning by testing the effect of a single infusion of 0.5 mg/kg of N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine on gamma band EEG (for NMDAR target engagement), other EEG markers, and on symptoms of Gulf War Illness in 19 cases. Outcomes will provide evidence of an expected neural excitatory and pro-inflammatory state in cases that could predispose to neuronal damage via NMDAR hyperactivation through kynurenine pathway activation, and will provide evidence in humans of possible effects of temporarily blocking NMDARs with a subanesthetic dose (0.5 mg/kg) of ketamine.