EFFECT OF DEEP BRAIN STIMULATION OF THE SUBTHALAMIC NUCLEUS IN LITHIUM-PILOCARPINE STATUS EPILEPTICUS OF RATS: THE FUNCTIONAL ANATOMY USING FOS IMMUNOHISTOCHEMISTRY
Abstract number :
1.103
Submission category :
Year :
2004
Submission ID :
998
Source :
www.aesnet.org
Presentation date :
12/2/2004 12:00:00 AM
Published date :
Dec 1, 2004, 06:00 AM
Authors :
Young Min Shon, Yeong In Kim, and Dong Won Yang
Currently, STN is presented as a new target of DBS for the anticonvulsant treatment, but its exact mechanism and route of action has not been elucidated yet. Seizure-induced Fos protein expression has been used extensively to identify spatially and temporally distributed neural systems activated by seizures. We investigated the effect of STN stimulation on the development and propagation of seizures in the rats with lithium-pilocarpine induced status epilepticus in course of disclosing its functional anatomy. Bipolar electrodes were inserted on the bilateral STN 7 days before pilocarpine injection (30mg/kg) with lithium pretreatment. After conditioning electrical stimulation (about 3min), both pilocarpine injection and STN DBS was provided to rats under the EEG recording (group A, n=15) with only injection on sham group (group B, n=10). Time to first discrete spikes, clinical seizure onset and seizure patterns (limbic seizure and/or generalized convulsion) were analyzed and the electrical stimulation was continued for 30, 60, 90, 120, 150 minutes after its first discrete spikes. After stimulation, the rats were immediately killed for immunohistochemistry and histologic examination. Marked prolonged latency for discrete spikes was seen in the group A (41.3[plusmn]20.7 min vs. 30.0[plusmn]7.8 min in group B) (p[lt]0.01). All rats showed discrete spikes and clinical seizures by 90minutes after pilocarpine injection, but only 6 rats showed generalized convulsion in group A (40%) in contrast to 9 rats in group B (90%) (p[lt]0.01). Early Fos immunoreactivity was seen in the regions including the piriform and entorhinal cortex, hippocampus, the amygdala, and the anterior and medial thalamic nucleus (limbic system) in both groups. In group A, the rats without generalized convulsion showed a decreased staining on the thalamic regions (ventrolateral nucleus, ventroposterolateral and ventroposteromedial nuclei) and their associated cortical regions. No definite changes were seen in the paraventricular, centromedial, and ventrolateral geniculate nuclei. We found that STN DBS in lithium-pilocarpine induced status model may suppress ictal propagation to generalized convulsion and delay its beginning but can not prevent seizure onset. Decreased immunoreactivity in the thalamic areas during DBS suggested the activation of STN efferent to substantia nigra pars reticulata (SNpr) which inhibit lateral parts of thalamic nuclei. Although unreliable Fos induction in the SNpr during limbic seizures, SNpr may be a key structure modulating seizure propagation during STN DBS via thalamo-cortical inhibition.