Abstracts

RATIONALE: There are some evidences from experimental animal studies that high-frequency subthalamic nucleus (STN) stimulation suppress substantia nigra pars reticulata (SNr) and it lead to suppress seizures. However, it is not well documented how SNr suppress the seizure. In this study, we analyzed that the changes in cerebral glucose metabolism of during high-frequency STN stimulation in kainic acid induced seizures using autoradiography.
METHODS: Male Wistar rats weighing between 260g and 320g were experimented. They were stereotactically implanted a stainless-steel cannula (0.6mm in diameter) into the left motor cortex and a bipolar electorode (0.2mm in diameter) into the ipsilateral STN under halothene anesthesia. Seven days after the surgery, kainic acid (2.0ug) was microinjected into the motor cortex via the cannula to induce seizure. The stimulation was started when the rat developed to seizure status clinically and continued to the end of experiment. The stimulation parameters were biphasic square pulse, pulse width was of 0.1ms, and frequency of 130Hz. The intensity was set to 70% of the threshold of motor symptom in each animal. The [14C]-2-deoxy-D-glucose ([14C]-2-DG) (25uCi) was intravenously injected 10 minutes after the beginning of the stimulation. Arterial blood was sampled over the subsequent 45 minutes. The rats were sacrificed as soon as last blood sampling was finished, and then the brain was quickly removed and frozen. The autoradiogram was made with coronal section of the brain. Changes in local cerebral metabolism were compared between the rat of STN stimulation and the control.
RESULTS: Seizures were induced by kainic acid in all rats, and the seizures were suppressed by high-frequency STN stimulation. In STN stimulation rats, seizure-induced hypermetabolism was suppressed in the thalamus, substantia nigra and caudate-putamen. In control, local glucose utilization was increased not only in the site of kainic acid-injected cortex but also in the various structures including the SNr.
CONCLUSIONS: Unilateral STN stimulation led to inhibition of the seizure-induced hypermetabolism in the ipsilateral SNr, thalamus and caudate-putamen. This result supports that STN stimulation can activate the nigral control system in epilepsy, and suggests that antiepileptic mechanism of STN stimulation may correlate with the inhibition of neuronal activities in the thalamus and caudate-putamen.