Establishment of animal model of myoclonus originating from axis of cortex-thalamus

Abstract

To develop a series of experimental animal models of myoclonus with different origins consistent with myoclonus seizure in clinic setting. GABA(A) antagonist SR95531 was microinjected into the primary motor cortex (PMC), corpus striatum, nucleus reticular of the thalamus (NRT) to induce myoclonus (EMG burst of myoclonus <or= 400 ms). The behavior characteristics including latency, peak time, duration of seizure peak, maximal seizure frequency and total duration were observed. EMGs and ictal EEGs were recorded synchronously. The origin of myoclonus and its correlation with epileptic discharges were further confirmed by jerk-locked back averaging (JLA). A group of rats were pretreated with VPA, CZP and CBZ at the doses corresponding to their EC(50). Myoclonus was induced at the time when the drug level was within their effective anticonvulsion concentration. The changes of behaviors and neuroelectrophysiological characteristics of myoclonus after pretreatment of AEDs were observed. (1) The myoclonus originating from PMC had the shortest latency and time to reach its peak as well as the longest duration of peak duration [(2.2 +/- 0.4), (15.0 +/- 2.5), (98 +/- 12) min]. The myoclonus originating from PMC and corpus striatum usually started from forelimb contralateral to injection. On the contrary, the myoclonus arising from NRT affected mainly the limb ipsilateral to the microinjection. (2) The EMG burst duration of myoclonus was (70 +/- 14) ms (PMC), (120 +/- 28) ms (corpus striatum) and (174 +/- 58) ms (NRT) respectively (F = 9.48, P < 0.01). All of them were accompanied with synchronic and regular spike or sharp discharges in EEG. (3) All the myoclonus originating from PMC, corpus striatum and NRT acquired time-locked cortical waves in average were ahead of their synchronous EMG (12.1 +/- 2.9) ms, (17.1 +/- 4.3) ms and (29.0 +/- 6.1) ms respectively. (4) Under EC(50) concentration of those AEDs: VPA and CZP decreased the maximal seizure frequency of myoclonus originating from PMC, corpus striatum and NRT respectively (P < 0.01 or P < 0.05); the duration of peak time and the total time of myoclonus arising from PMC and corpus striatum were shortened notably, but there was no significant influence of NRT upon myoclonus. The duration of peak time and total time of myoclonus seizures were remarkably extended by CBZ (P < 0.01 or P < 0.05). A series of experimental myoclonus models of different origins are successfully established. They are consistent with the mechanism, behavior, neuroelectrophysiological and pharmacodynamic characteristics of clinic myoclonus.