A comparison of anticonvulsant efficacy and action mechanism of Mannitol vs Phenytoin in adult rat neocortical slices

We show that, in adult rat neocortical slices, an anticonvulsant effect comparable to that of Phenytoin can be obtained through a Mannitol-induced increase in extracellular osmolarity of only 30 mOsm/L. The anticonvulsant action of extracellular hyperosmolarity has been known for decades but has not found a feasible therapeutic application, yet. A 30 mOsm/L increase in extracellular osmolarity is already utilized in neurocritical care though not as an anticonvulsant agent: the data suggest a possible effective anticonvulsant use, too, in this setting. We used multiple electrode arrays to characterize and compare the anticonvulsant mechanisms of Mannitol and Phenytoin. Phenytoin decreased the voltage, duration and spatial spread of rhythmic repetitive, ictal-like activity. In contrast, Mannitol did not significantly affect voltage, duration and spatial spread of rhythmic repetitive, ictal-like activity but rather it inhibited the rate of epileptiform discharges.