title: Deep brain stimulation of the substantia nigra pars reticulata exerts long lasting suppression of amygdala-kindled seizures.
abstract: Deep brain stimulation (DBS) has been used to treat a variety of neurological disorders including epilepsy. However, we have limited knowledge about effective target areas, optimal stimulation parameters, and long-term effect of DBS on epileptic seizures. Here we examined the effects of DBS of the substantia nigra pars reticulata (SNr) on amygdala-kindled seizures. Microwire electrodes were implanted into the SNr and amygdala of adult male rats. When stage 5-kindled seizures were achieved by daily amygdala kindling, high frequency stimulation was delivered to the SNr bilaterally 1 s after cessation of kindling. Our DBS protocol completely blocked kindled seizures in 10 out of 23 (43.5%) rats studied. Furthermore, when the same amygdala kindling procedure was performed 24 h later without DBS, the kindling failed to elicit any seizure signs in 6 of these 10 rats. Some of the post-DBS period of seizure suppression lasted for up to 4 days. In other 3 rats, only mild stage 1 to 2 seizures appeared following amygdala kindling. Only 1 of the 10 rats for which DBS had blocked kindled seizures exhibited full-scale 5 stage-kindled seizures 24 h after DBS. These results suggest that highly plastic neural networks are involved in amygdala-kindled seizures and that DBS, if well timed with the onset of amygdala kindling, may exert long lasting effects on the networks that may prevent the recurrence of kindled seizures.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Shi
authors.forename: Fei
authors.initials: F
authors.lastname: Luo
authors.forename: Donald
authors.initials: D
authors.lastname: Woodward
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Chang
mesh_terms: D000679:Amygdala / Q000503:physiopathology*; D000818:Animals; D046690:Deep Brain Stimulation / Q000379:methods* / Q000639:trends; D004567:Electrodes, Implanted / Q000592:standards; D004827:Epilepsy / Q000503:physiopathology* / Q000628:therapy*; D007696:Kindling, Neurologic / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology; D008297:Male; D009415:Nerve Net / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D013995:Time; D013997:Time Factors; D016896:Treatment Outcome