Chronic bilateral stimulation of the anterior thalamus of kainate-treated rats increases seizure frequency.
OBJECTIVE
Electrical stimulation of the anterior nucleus of the thalamus (ANT) is receiving increased attention as a novel means of controlling intractable epilepsy, and has entered human clinical trial. Animal data supporting the anticonvulsant benefit of ANT stimulation, however, has been obtained from acute chemoconvulsant models of epilepsy rather than models of chronic epilepsy with spontaneous seizures. It is unknown whether ANT stimulation is effective in models of chronic epilepsy.


METHODS
Bilateral ANT stimulation was evaluated in rats with chronic epilepsy following acute status epilepticus (SE) produced by systemic kainic acid (KA) administration. The evolution of epilepsy following KA SE and the effects of ANT stimulation were monitored by continuous video-EEG.


RESULTS
Following KA SE, most rats have 2-8 seizures per day, and the average seizure rate increases over time, doubling over the course of 14 weeks. Behavioral seizure severity, after the initial development of epilepsy, remains stable. Seizure frequency during ANT stimulation was 2.5 times the baseline seizure frequency. In some cases stimulation triggered seizures were observed. The effects of stimulation were specific to the ANT. Stimulation applied to electrodes placed outside the ANT did not significantly worsen seizure frequency.


CONCLUSIONS
ANT stimulation exacerbated seizure frequency in rats with chronic epilepsy following kainate status epilepticus.
Lado
Fred A
FA
Department of Neurology and the Comprehensive Epilepsy Management Center, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York 10461, USA. flado@aecom.yu.edu
D000208:Acute Disease; D000818:Animals; D020643:Anterior Thalamic Nuclei / Q000502:physiology* / Q000503:physiopathology; D046690:Deep Brain Stimulation / Q000009:adverse effects / Q000379:methods; D004195:Disease Models, Animal; D004599:Electric Stimulation Therapy / Q000009:adverse effects* / Q000379:methods*; D004569:Electroencephalography / Q000187:drug effects / Q000706:statistics & numerical data*; D004827:Epilepsy / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology; D007839:Functional Laterality / Q000502:physiology*; D007608:Kainic Acid; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced* / Q000175:diagnosis* / Q000503:physiopathology; D012720:Severity of Illness Index; D013226:Status Epilepticus / Q000139:chemically induced* / Q000503:physiopathology; D014743:Videotape Recording
D007608:Kainic Acid