Abstracts

Stimulation of aplha2-adrenoceptors delays the development of kindling, a model of epileptogenesis in humans. Blocking alpha2-adrenoceptors is proconvulsant, but has beneficial effects on somatomotor recovery after experimental stroke. We investigated whether atipamezole, a selective alpha2-adrenoceptor antagonist, affects the recovery process from status epilepticus (SE) -induced brain trauma, which affects the risk of epileptogenesis.
Vehicle or atipamezole (100 micrograms/kg/h) treatment was started 1 wk after the induction of SE by electrical stimulation of the amygdala and continued for 9 wk using Alzet minipumps (n=70). Occurrence and severity of seizures were monitored by video-EEG recording during and after treatment. Development and severity of epilepsy, spatial (Morris water maze) and emotional (fear conditioning to tone and context) learning, and histologic analysis (hilar cell loss, mossy fiber sprouting) were used as outcome measures.
There were no differences in the percentage of animals with epilepsy in the different treatment groups. In the atipamezole group, however, daily seizure frequency was lower (p[lt]0.01), a higher percentage of epileptic animals had mild epilepsy (less than 1 seizure/day; p[lt]0.01), and seizure frequency did not increase over time compared with the vehicle group. The atipamezole group had milder hilar cell damage (p[lt]0.05) and less intense mossy fiber sprouting (p[lt]0.05). Behavioral impairments were similar between groups.
Our data indicate that chronic treatment with atipamezole does not totally prevent epileptogenesis. There is, however, a clear disease-modifying effect; that is, the epilepsy that develops is milder and non-progressive. These are the first data to demonstrate that the occurrence of spontaneous seizures can be modified even when treatment is started after a delay relative to the epileptogenic insult.
[Supported by: Orion Pharma]