Abstracts

RATIONALE: We developed an in vitro model of traumatic brain injury to investigate hyperexcitability and epileptogenesis, and their prevention. In this study we used the model to explore altering electronic coupling via gap junctions on network excitability in this model.
METHODS: Rat neocortical slices (450 [mu]m thick) were prepared and maintained in vitro using standard methods. Trauma was effected by removing the third superficial layers (about 450-500 [mu]m from pia) in coronal slices. The slices were placed in an interface chamber (30[degree] C), exposed to humidified 95% O[sub]2[/sub] and 5% CO[sub]2[/sub]. Intracellular and extracellular recordings were used to assess synaptic responses. Carbenoxolone (CarX, 200 [mu]M) and trimethylamine (TMA;15 mM) were bath applied to uncouple, or to strengthen gap junction communication, respectively.
RESULTS: Typical epileptiform activities were seen in most (80%) traumatized slices, i.e., evoked paroxysmal discharges in intracellular and field potentials, as previously reported. CarX shortened, or abolished such paroxysmal discharges, and these effects were reversible. TMA treatment prolonged the duration of epileptiform activities, and increased the number of repetitive afterdischarges. In the presence of TMA, CarX also shortened or abolished epileptiform discharges. Limited exposure of traumatized slices to CarX for 1 hr following injury did not prevent the epileptiform activity from developing, although valproate or pentobarbital were proven effective using this protocol.
CONCLUSIONS: (1) Electronic coupling appears to participate in generating the hyperexcitability in acutely damaged neuronal networks, and modulation of coupling can effectively bias excitability. (2) Targeted blockade of gap junction communication may be a potential treatment for posttraumatic seizure activity (anticonvulsant), but does not appear to be effective in preventing the development of this activity (antiepileptogenic).
Support: MH01431 and NS38132