Abstracts

RATIONALE: To determine the mechanism of anticonvulsant action of subthalamic electrical stimulation.
METHODS: Concentric bipolar stimulation electrodes were implanted unilaterally in the subthalamic nucleus of adult male rats. Rats were allowed to recover 48 hours after surgery, and were then fasted overnight. On the day of testing, rats received 0.5mCurie/kg dose of 14C-2-deoxyglucose subcutaneously at the onset of continuous 130 Hz electrical stimulation. Stimulation consisted of a 130Hz train of 60[mu]s bipolar rectangular waves (30[mu]s per half-wave) lasting 45 minutes delivered to the electrode implanted in the subthalamic nucleus. Stimulation intensity was adjusted in each animal to the maximum level that did not produce motor side effects. At the conclusion of stimulation, each animal was rapidly decapitated, and the brain was removed and rapidly frozen at [ndash]35C. Brains were sectioned into 40[mu]m slices which were exposed to autoradiography film for 7-days. Resultant images were scanned using a flatbed scanner at 1200 dpi, and images were analyzed using NIH Image (as adapted for the PC by Scion, Inc). Calculated values included the ratio of intensities between the specific structures ipsi and contralateral to the site of stimulation and the entire section of brain containing the structure. ANOVA analysis was used to determine whether the relative intensities of glucose utilization differed between stimulated animals and unstimulated controls, and between ipsi- and contralateral structures.
RESULTS: 130 Hz subthalamic stimulation significantly increased glucose utilization ipsilaterally in the subthalamic nucleus, globus pallidus, substantia nigra pars reticulata, and the superior colliculus.
CONCLUSIONS: 130 Hz electrical stimulation increases activation in the subthalamic nucleus and in nuclei receiving subthalamic input directly and indirectly, via polysynaptic pathways. Subthalamic stimulation may increase the seizure threshold by activating extrapyramidal circuits rather than by inhibiting subthalamic neurons.
[Supported by: NIH grant K08-NS41340 (FAL), NIH grant NS-20253(SLM), SURP fellowship from the Albert Einstein College of Medicine(JA)]; (Disclosure: Grant - F. Lado has a unrestricted educational grant from Medtronic, Inc. that is being used to fund separate research (i.e. not the data discussed in this abstract) into the effects of thalamic and subthalamic electrical stimulation on seizures.)