Abstracts

RATIONALE: Somatostatin-28 (SS), neuropeptide Y (NPY), dynorphin-A-1-13 (DYN, and galanin (GAL) are abundant in the hippocampus and counteract seizure activity in a number of epilepsy models. We compared anticonvulsant efficacy of these neuropeptides in a model of self-sustaining status epilepticus (SSSE)in the rat.
METHODS: Male Wistar rats were implanted with a bipolar recording electrode/cannula into the ventral dentate gyrus, and with a bipolar stimulating electrode into the perforant path. SSSE was induced by 30 min intermittent perforant path stimulation (PPS) with 10 s 20 Hz trains delivered every minute. SS, NPY, DYN, GAL or saline were injected into the hilus 10 min after the end of PPS. EEG was analyzed utilizing Harmonie software (Stellate systems). Time spent in seizures, time of the occurrence of the last seizure, spike frequency over 30 min epochs, and the time of the occurrence of the last spike were calculated.
RESULTS: All neuropeptides attenuated SSSE in doses of 1 and 5, but not 0.1 nmol. After SS and NPY time spent in seizures was 4-5 hrs and the last seizure was recorded 6-8 hrs after peptide injection (p[lt]0.05 vs Control). DYN and GAL produced significantly more profound suppression of SSSE, the duration of which never exceeded 20 min and total time spent in seizures under 10 min (p[lt]0.05 vs Control, NPY, or SS).
All neuropeptides induced spike depression in the following rank order: DYN=GAL[gt]SS=NPY.
SS and NPY showed a similar pattern of the effect on both seizures and spikes. Immediately after injection, both peptides almost completely eliminated both spikes and seizures. However, after 2-3 hrs, seizure frequency increased and was comparable to that in control group for the next 3 hrs. Afterwards, the second decline in seizure frequency was observed, and seizures disappeared within 8 hrs after PPS. Similarly to seizures, spike frequency significantly dropped immediately after SS or NPY administration. However, 2-4 hrs after PPS, the spike frequency increased again, and spikes stayed within the same frequency as in control group until the end of SSSE (up to 24 hrs).
Administration of DYN and GAL produced a different effect. Both peptides induced fast (within 20 min) disappearance of seizures, and suppression of spikes within 10 min after administration. In contrast to SS and NPY, suppression of both seizures and spikes by DYN and GAL was irreversible.
CONCLUSIONS: All four neuropeptides showed significant seizure protecting effect in an animal model of SSSE. The anticonvulsant profile of neuropeptides followed different patterns. While SS and NPY produced less profound and transient effects on seizures, DYN and GAL strongly and irreversibly suppressed SSSE-related ictal events.
Support: Grants NS 11315 from NIH and by the Research Service of VHA.