Does prolonged implantation of depth electrodes predispose the brain to kindling?
Chronically implanted depth electrodes are widely used for the study of electrical signals generated in deep cerebral locations and for electrical stimulation of such locations. Although the effects of lesions resulting from electrode implantation are generally considered minimal, some reports have shown lasting neurochemical, histological, and behavioral alterations in response to such implantation. Furthermore, there is some evidence that prolonged electrode implantation may decrease the seizure threshold of the implanted region and increases the rate of kindling from this region. This prompted us to undertake a study on different periods of post-surgical delay to onset of electrical stimulation and subsequent characteristics of kindling development. Rats were implanted with a bipolar electrode in the basolateral amygdala, and the threshold for induction of focal paroxysmal activity (afterdischarge threshold, ADT) was determined after post-surgical recovery periods of either 1, 2, 4, or 8 weeks. The animals were then kindled by daily administration of an electrical stimulus until all rats exhibited fully kindled seizures. In fully kindled rats, the ADT was redetermined. Compared to animals with 1 week of electrode implantation, the pre-kindling ADT was significantly lower in rats with 2 and 4 weeks of electrode implantation, but returned towards the 1 week values at 8 weeks. An enhanced kindling rate was seen when kindling stimulations were started after 4 and 8 weeks of electrode implantation. Despite the marked differences in pre-kindling ADT, the post-kindling ADT was similar in the groups with 1, 2, or 4 weeks but significantly lower in the group with 8 weeks post-surgical delay to onset of testing. The data suggest that prolonged implantation of a bipolar electrode into a sensitive region of the limbic system predisposes the brain to kindling. Based on previous observation of iron deposits induced by electrode implantation and the epileptogenic effect of iron in cortical and limbic regions, we propose that the present observations are due to deposition of iron from hemoglobin destruction in local microhemorrhages caused by the implantation.
Löscher
W
W
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
Wahnschaffe
U
U
Hönack
D
D
Rundfeldt
C
C
D000818:Animals; D001921:Brain / Q000502:physiology*; D004056:Differential Threshold; D004567:Electrodes, Implanted; D004594:Electrophysiology; D005260:Female; D007696:Kindling, Neurologic; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors