Subtle alterations in NMDA-stimulated cyclic GMP levels following lateral fluid percussion brain injury

This study examined whether NMDA-stimulated cyclic GMP levels were altered at two different time points following lateral fluid percussion injury. At 60 min and 15 days postinjury, the left and right hippocampi were dissected and chopped into mini-prisms. Each hippocampus was divided into five equal parts and incubated with either the phosphodiesterase inhibitor IBMX (3-is obutyl-1-methylxanthine, 500 muM) alone, IBMX and N-methyl-D-aspartic acid (NMDA) OR IBMX, NMDA, and glycine (10 MM), Two concentrations of NMDA were used: 500 or 1,000 muM, Tissues were then assayed for levels of cyclic GMP, Results indicated that there were no changes in basal levels of cyclic GMP at either postinjury time point. At 60 min postinjury, there were no signi ficant main effects for injury or drug concentration. There was a significa nt injury x side interaction effect with increased levels of NMDA-stimulate d cyclic GMP in the hippocampus ipsilateral to the injury impact and decrea sed cyclic GMP levels in the contralateral hippocampus. There were no signi ficant alterations in NMDA-stimulated cyclic GMP levels at 15 days postinju ry, The data from this study indicated that NMDA-stimulated cyclic GMP accu mulation is differentially altered in the hippocampus ipsilateral and contr alateral to the site of the injury at 1 h after injury, but is normalized b y 15 days postinjury, These findings implicate NMDA-mediated intracellular signaling processes in the acute excitotoxic response to injury.