VOLTAGE-DEPENDENT NA+ K+ ION-CHANNEL BLOCKADE FAILS TO AMELIORATE BEHAVIORAL DEFICITS AFTER TRAUMATIC BRAIN INJURY IN THE RAT/

Traumatic brain injury (TBI) induces massive, transient ion flux, afte r impact. This may be via agonist gated channels, such as the muscarin ic, cholinergic or NMDA receptor, or via voltage-dependent channels. P harmacological blockade of the former, is neuroprotective in most TBI models, but the role of voltage-dependent Na+/K+ channels has not been tested. We have therefore tested the hypothesis that intraventricular tetrodotoxin (TTX) (20 mu l, 5 mM) induced blockade of post-TBI ion f lux will prevent cytotoxic cell swelling, Na+ and K+ flux, and behavio ral deficit. Microdialysis demonstrated blockade of [K+]d flux in the TTX group compared to controls. Behavioral evaluation of motor (days 1 -5) and memory function (days 11-15) after TBI revealed no beneficial effect in the TTX group compared to controls. Thus, although evidence of reduced ionic flux was demonstrated in the TTX group, memory and be havior were unaffected, suggesting that agonist-operated channel-media ted ion flux is more important after TBI.