Deep brain stimulation of the anterior nucleus of the thalamus: Effects of electrical stimulation on pilocarpine-induced seizures and status epilepticus

Hamani, Clement; Hodaie, Mojgan; Chiang, Jason; del Campo, Martin; Andrade, Danielle M.; Sherman, David; Mirski, Marek; Mello, Luiz E.; Lozano, Andres M.

doi:10.1016/j.eplepsyres.2007.09.010

« Previous Next »Epilepsy Research
Volume 78, Issue 2 , Pages 117-123, February 2008

Deep brain stimulation of the anterior nucleus of the thalamus: Effects of electrical stimulation on pilocarpine-induced seizures and status epilepticus

Clement Hamani
- Division of Neurosurgery, Toronto Western Hospital and University Health Network, University of Toronto, Toronto, Ontario, Canada
- Department of Physiology, Universidade Federal de São Paulo, São Paulo, Brazil
- Both authors contributed equally to this study.
Mojgan Hodaie
- Division of Neurosurgery, Toronto Western Hospital and University Health Network, University of Toronto, Toronto, Ontario, Canada
- Toronto Western Hospital Research Institute, Krembil Neuroscience Center, Toronto, Ontario, Canada
- Both authors contributed equally to this study.
- Corresponding author at: Division of Neurosurgery, Toronto Western Hospital, University Health Network, 4WW-443, 399 Bathurst Street, Toronto, ON, Canada M5T 2S8. Tel.: +1 416 603 6441; fax: +1 416 603 5298.
Jason Chiang
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States
Martin del Campo
- Division of Neurology, Toronto Western Hospital and University Health Network, University of Toronto, Toronto, Ontario, Canada
Danielle M. Andrade
- Division of Neurology, Toronto Western Hospital and University Health Network, University of Toronto, Toronto, Ontario, Canada
David Sherman
- Johns Hopkins University School of Medicine, Baltimore, MD, United States
Marek Mirski
- Johns Hopkins University School of Medicine, Baltimore, MD, United States
Luiz E. Mello
- Department of Physiology, Universidade Federal de São Paulo, São Paulo, Brazil
Andres M. Lozano
- Division of Neurosurgery, Toronto Western Hospital and University Health Network, University of Toronto, Toronto, Ontario, Canada
- Toronto Western Hospital Research Institute, Krembil Neuroscience Center, Toronto, Ontario, Canada

Received 10 May 2007; received in revised form 10 August 2007; accepted 22 September 2007.

Summary

Purpose

Electrical stimulation of the anterior nucleus of the thalamus appears to be effective against seizures in animals and humans. As the optimal stimulation settings remain elusive, we studied the effects of different stimulation parameters against pilocarpine induced seizures and status epilepticus (SE).

Methods

Adult rats had electrodes implanted bilaterally into the AN. Five days later, different groups of animals were stimulated with 1000μA, 500μA, or 200μA and frequencies of either 20Hz or 130Hz. Pilocarpine (350mg/kg i.p.) was injected 5min after stimulation onset and seizures were monitored. Sham-treated controls had electrodes implanted but did not receive stimulation until they developed SE. After SE, these animals had the electrodes turned on to assess whether AN stimulation could arrest ongoing ictal activity.

Results

Compared to sham-treated controls (n=8), stimulation at 500μA (n=13) significantly increased the latency for seizures and SE by 1.9–2.2-fold. In contrast, stimulation at 1000μA (n=8) produced a non-significant decrease in the latencies to these events. No major effect was observed with stimulation at 200μA (n=11). Similar results were obtained for each current intensity, regardless of the stimulation frequency used (20Hz and 130Hz). In sham-treated controls that had the electrodes turned on after SE, stimulation was not able to arrest ongoing ictal activity.

Conclusions

The anticonvulsant effects of AN stimulation against pilocarpine-induced seizures were mainly determined by the current and not the frequency of stimulation. AN stimulation initiated after SE onset was ineffective.

Keywords: Deep brain stimulation, Anterior thalamic nucleus, Pilocarpine, Status epilepticus, Stimulation parameters