Deep brain stimulation of the anterior nucleus of the thalamus: effects of electrical stimulation on pilocarpine-induced seizures and status epilepticus.
OBJECTIVE
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 1000 microA, 500 microA, or 200 microA and frequencies of either 20 Hz or 130 Hz. Pilocarpine (350 mg/kg i.p.) was injected 5 min 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 500 microA (n=13) significantly increased the latency for seizures and SE by 1.9-2.2-fold. In contrast, stimulation at 1000 microA (n=8) produced a non-significant decrease in the latencies to these events. No major effect was observed with stimulation at 200 microA (n=11). Similar results were obtained for each current intensity, regardless of the stimulation frequency used (20 Hz and 130 Hz). 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.
Hamani
Clement
C
Division of Neurosurgery, Toronto Western Hospital and University Health Network, University of Toronto, Toronto, Ontario, Canada.
Hodaie
Mojgan
M
Chiang
Jason
J
del Campo
Martin
M
Andrade
Danielle M
DM
Sherman
David
D
Mirski
Marek
M
Mello
Luiz E
LE
Lozano
Andres M
AM
D000818:Animals; D020643:Anterior Thalamic Nuclei / Q000502:physiology*; D046690:Deep Brain Stimulation; D004558:Electric Stimulation; D004569:Electroencephalography / Q000187:drug effects; D008297:Male; D018721:Muscarinic Agonists; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy*; D013226:Status Epilepticus / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy*
D018721:Muscarinic Agonists; D010862:Pilocarpine