Abstracts

RATIONALE: Limbic motor seizures in animals activate the mediodorsal thalamic (MD) nucleus and, concomitant with status epilepticus always damage to the MD thalamic nucleus. The MD thalamic nucleus connected with almost all limbic structures is thought to have an important role in the epileptogenesis and the propagation of limbic motor seizures. A number of studies have demonstrated that manipulation of excitatory / inhibitory neurotransmission within this nucleus can suppress the expression of limbic seizures in experimental animals.In many patients with intractable epilepsy, electrical stimulation of the selected brain structure have been considered as a therapeutic option to prevent the initiation or propagation of seizure expression, but there are many difficulties in defining suitable region for effective stimulation.
METHODS: This study using pilocarpine-induced seizure model examined the effect of electrical stimulation of the thalamic MD nucleus on the expression of limbic seizures in rats. After placing bipolar stimulating steel electrodes within the MD thalamic nucleus of the Sprague-Dawley rats, electrical stimulation was delivered using high-frequency stimulation (i.e. frequency=180Hz, intensity range=500-600[mu]A. We examined the changes of clinical seizure and EEG findings induced by pilocarpine, and microscopic structures involved in propagation of the seizure activity and neuroprotective effects in hippocampus using Fos-immunohistochemical staining and Hematoxyline-Eosin staining.
RESULTS: Electrical stimulation of the MD thalamic nucleus suppressed seizures to the focal limbic seizures without expressing generalized seizure or status epilepticus, and EEG revealed intermittent ictal discharges without continuous ictal discharges typical of pilocarpine-induced seizures. Immunohistochemical staining showed different distribution of the expression of Fos protein according to the clinical seizure stages; Fos protein was expressed in the piriform cortex and amygdala even in the focal limbic seizures, but expressed in midline thalamus only during the generalized seizures or status epilepticus. Electrical stimulation of the MD thalamic nucleus also markedly reduced the number of damaged cells in hippocampus.
CONCLUSIONS: These results indicate that in pilocarpine-induced limbic seizure, high-frequency electrical stimulation of the MD thalamic nucleus cannot block the epileptogenesis in the piriform cortex region, but has an effect of suppressing the propagation of seizure activity to the other brain structures through the thalamus including the MD nucleus. Therefore, electrical stimulation of the MD thalamic nucleus can be useful in control of intractable epilepsy.
Support: The Catholic Medical Center Research Foundation.