Effects of Lateral Cerebellar Nucleus Stimulation on Seizures in Rats Kindled to Different Levels of Seizure Severity with PTZ

Abstract

Abstract Background In recent years, the cerebellum and its nuclei have become important targets for understanding and suppressing the mechanisms of seizures. The aim of this study was to investigate the effects of electrical stimulation (ES) applied to the lateral cerebellar nucleus (LCN) in rats with early and fully developed pentylenetetrazol (PTZ)-kindled seizures. MethodsThe experimental groups were represented by rats kindled with PTZ (35.0 mg/kg, i.p.) to myoclonus (9-11 PTZ injections) and generalized tonic-clonic seizures (21 PTZ injections). Unilateral ES (100 Hz, 0.25 ms, 4.5-5.0 duration) was delivered daily for five days after the last kindled PTZ administration with PTZ seizure testing after the last ES. Results ES of LCN performed at the early stage of kindling facilitated the appearance of myoclonus and increased seizure severity by 30.2% - up to 2.25+0.46 scored points compared to the control group (P<0.05). In fully developed kindling, ES prevented generalized seizure and reduced seizure severity by 27.5% - to 3.11+0.31 scored points (P<0.02). In both groups,spikes in the frontal and ventral hippocampus corresponding to myoclonuswere noticed. The linear density of PC in the cerebellar hemisphere cortex was reduced to 9.67±1.12in fully kindled rats, while in the control group, it was 20.17±2.10 per mm (P<0.05). Conclusion The data obtained showed that repeated ES of the LCN at the early kindling stage facilitates myoclonus appearance, while in fully PTZ-kindled rats causes suppression of generalized seizure fits, which were substituted with myoclonus.