The effects of traumatic brain injury on inhibition in the hippocampus and dentate gyrus

• Published in: Brain research Vol. 757; no. 1; pp. 119 - 132
• Main Authors: Reeves, Thomas M., Lyeth, Bruce G., Phillips, Linda L., Hamm, Robert J., Povlishock, John T.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 16.05.1997
• Subjects: Animals; Brain Injuries - physiopathology; Dentate gyrus; Dentate Gyrus - physiology; Dentate Gyrus - physiopathology; Electric Stimulation; Evoked Potentials; Functional Laterality; gamma-Aminobutyric Acid - metabolism; Hippocampus; Hippocampus - physiology; Hippocampus - physiopathology; Male; Neuronal Plasticity; Neurons - physiology; Paired-pulse inhibition; Pyramidal Cells - physiology; Rat; Rats; Rats, Sprague-Dawley; Synaptic Transmission; Time Factors; Traumatic brain injury; γ-Aminobutyric acid; Paired-pulse inhibition; Dentate gyrus; γ-Aminobutyric acid; Traumatic brain injury; Rat; Hippocampus
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(97)00170-4

Changes in inhibitory neuronal functioning may contribute to morbidity following traumatic brain injury (TBI). Evoked responses to orthodromic paired-pulse stimulation were examined in the hippocampus and dentate gyrus at 2 and 15 days following lateral fluid percussion TBI in adult rats. The relative strength of inhibition was estimated by measuring evoked paired pulses in three afferent systems: the CA3 commissural input to the CA1 region of the hippocampus; the entorhinal cortical input to the ipsilateral CA1 area (temporoammonic system); and the entorhinal input to the ipsilateral dentate gyrus (perforant path). In addition to quantitative electrophysiological estimates of inhibitory efficacy, levels of γ-aminobutyric acid (GABA) were qualitatively examined with immunohistochemical techniques. Effects of TBI on paired-pulse responses were pathway-specific, and dependent on time postinjury. At 2 days following TBI, inhibition of population spikes was significantly reduced in the CA3 commissural input to CA1, which contrasted with 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 depended on fiber pathway and time postinjury. Significant injury-induced electrophysiological changes were almost entirely confined to the hemisphere 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 found in the dentate gyrus. TBI-induced effects showed a regional pattern within the hippocampus which corresponds closely to inhibitory changes reported to follow ischemia and kindling. This degree of similarity in outcome following dissimilar injuries may indicate common mechanisms in the nervous system response to injury.