FELBAMATE NEUROPROTECTION AGAINST CA1 TRAUMATIC NEURONAL INJURY

Traumatic brain injury is a leading cause of disability and death. Sin ce the anticonvulsant felbamate provides hypoxic neuroprotection, we i nvestigated whether felbamate would provide protection against traumat ic neuronal injury as well. Traumatic injury to CA1 neurons in hippoca mpal slices was induced by fluid percussion, and CA1 evoked response w as monitored. Pre-treatment with felbamate was strongly protective aga inst neuronal injury, and permitted CA1 antidromic population spike re covery to a mean 94 +/- 1% (S.E.M.) of initial amplitude, compared to unmedicated slices which regained only 15 +/- 6%. The felbamate EC(50) for this protection was 136 mg/l, and significant protection was foun d at felbamate concentrations similar to those reported in felbamate m onotherapy for seizures. Significant protection was also defected when felbamate was initiated 15 min after trauma. Slices given brief post- trauma felbamate treatment could demonstrate long-term potentiation wh en assessed 8 h after trauma. These studies indicate that felbamate is neuroprotective against CA1 traumatic neuronal injury.