THE EFFECTS OF TRAUMATIC BRAIN INJURY ON INHIBITION IN THE HIPPOCAMPUS AND DENTATE GYRUS

Changes in inhibitory neuronal functioning may contribute to morbidity following traumatic brain injury (TBI). Evoked responses to orthodrom ic paired-pulse stimulation were examined in the hippocampus and denta te gyrus at 2 and 15 days following lateral fluid percussion TBI in ad ult rats. The relative strength of inhibition was estimated by measuri ng evoked paired pulses in three afferent systems: the CA3 commissural input to the CA1 region of the hippocampus; the entorhinal cortical i nput to the ipsilateral CA1 area (temporoammonic system); and the ento rhinal input to the ipsilateral dentate gyms (perforant path). In addi tion to quantitative electrophysiological estimates of inhibitory effi cacy, levels of gamma-aminobutyric acid (GABA) were qualitatively exam ined with immunohistochemical techniques. Effects of TBI on paired-pul se responses were pathway-specific, and dependent on time postinjury. At 2 days following TBI, inhibition of population spikes was significa ntly reduced in the CA3 commissural input to CA1, which contrasted wit h injury-induced increases in inhibition in the dentate gyrus seen at both 2 and 15 days postinjury. Low-level stimulation, subthreshold for population spikes, also revealed changes in paired-pulse facilitation of field extracellular postsynaptic potentials (fEPSPs), which depend ed on fiber pathway and time postinjury. Significant injury-induced el ectrophysiological changes were almost entirely confined to the hemisp here ipsilateral to injury. Intensity of GABA immunobinding exhibited a regional association with electrophysiological indices of inhibition , with the most pronounced increases in GABA levels and inhibition fou nd in the dentate gyrus. TBI-induced effects showed a regional pattern within the hippocampus which corresponds closely to inhibitory change s reported to follow ischemia and kindling. This degree of similarity in outcome following dissimilar injuries may indicate common mechanism s in the nervous system response to injury.