Felbamate neuroprotection against CA1 traumatic neuronal injury

Abstract

Traumatic brain injury is a leading cause of disability and death. Since the anticonvulsant felbamate provides hypoxic neuroprotection, we investigated whether felbamate would provide protection against traumatic neuronal injury as well. Traumatic injury to CA1 neurons in hippocampal slices was induced by fluid percussion, and CA1 evoked response was monitored. Pre-treatment with felbamate was strongly protective against neuronal injury, and permitted CA1 antidromic population spike recovery 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 found at felbamate concentrations similar to those reported in felbamate monotherapy for seizures. Significant protection was also detected when felbamate was initiated 15 min after trauma. Slices given brief post-trauma felbamate treatment could demonstrate long-term potentiation when assessed 8 h after trauma. These studies indicate that felbamate is neuroprotective against CA1 traumatic neuronal injury.