Long-term hyperexcitability in the hippocampus after experimental head trauma

Head injury is a causative factor in the development of temporal lobe epile psy. However, whether a single episode of concussive head trauma causes a p ersistent increase in neuronal excitability in the limbic system has not be en unequivocally determined. This study used the rodent fluid percussion in jury (FPI) model, in combination with electrophysiological and histochemica l techniques, to investigate the early (1 week) and long-term (1 month or l onger) changes in the hippocampus after head trauma. Low-frequency, single- shock stimulation of the perforant path revealed an early granule cell hype rexcitability in head-injured animals that returned to control levels by 1 month. However, there was a persistent decrease in threshold to induction o f seizure-like electrical activity in response to high-frequency tetanic st imulation in the hippocampus after head injury. Timm staining revealed both early- and long-term mossy fiber sprouting at low to moderate levels in th e dentate gyrus of animals that experienced FPI. There was a long-lasting i ncrease in the frequency of spontaneous inhibitory postsynaptic currents in dentate granule cells after FPI, and ionotropic glutamate receptor antagon ists selectively decreased the spontaneous inhibitory postsynaptic current frequency in the head-injured animals. These results demonstrate that a sin gle episode of experimental closed head trauma induces long-lasting alterat ions in the hippocampus. These persistent structural and functional alterat ions in inhibitory and excitatory circuits are likely to influence the deve lopment of hyperexcitable foci in posttraumatic limbic circuits.