ENHANCED PHOSPHODIESTRIC BREAKDOWN OF PHOSPHATIDYLINOSITOL BISPHOSPHATE AFTER EXPERIMENTAL BRAIN INJURY

Regional levels of lactate and inositol 1,4,5-trisphosphate (IP3), a c ellular second messenger of the excitatory neurotransmitter system, we re measured after lateral fluid percussion (FP) brain injury in rats. At 5 min postinjury, tissue lactate concentrations were significantly elevated in the cortices and hippocampi of both the ipsilateral and co ntralateral hemispheres. By 20 min postinjury, lactate concentrations were elevated only in the cortices and hippocampus of the ipsilateral hemisphere. Whereas the IP3 concentrations were elevated in the hippoc ampi of the ipsilateral and contralateral hemisphere and in the cortex of ipsilateral hemisphere at 5 min postinjury, no elevation in these sites was found at 20 min postinjury. Histologic analysis revealed neu ronal damage in the cortex and CA3 regions of hippocampus ipsilateral to the injury at 24 h postinjury. The present results suggest activati on of the phosphoinositide signal transduction pathway at the onset of injury and of a possible requirement of early persistent metabolic dy sfunction (>20 min) such as the lactate accumulation in the delayed ne uronal damage.