Abstracts

Rationale: tDCS is a noninvasive method for modulating cortical excitability by weak constant unidirectional electrical currents applied to the subject’s scalp. Recently, the capacity of tDCS to induce lasting changes in excitability has been explored as a therapeutic option in epilepsy where cathodal tDCS has been shown to reduce the frequency of epileptiform discharges in human subjects (Fregni et al., 2006), and to raise seizure threshold to electroshock in rat motor cortex (Liebetanz et al., 2006). However, the potential for tDCS modulate neuronal activity during ongoing seizures has not been extensively studied. Accordingly, we sought to determine whether anodal or cathodal tDCS can reduce seizure-induced expression of c-Fos, a product of an immediate early gene and a marker of excessive neuronal activation that is associated with seizures, in rats treated with the convulsant pentylenetetrazole (PTZ). Methods: We developed methods for tDCS in unanesthetized gently-restrained rats. Seizures were triggered by PTZ (25 mg/kg i.p.) injection in young (postnatal day 12) Long Evans rats. tDCS was applied through saline-saturated sponge electrodes secured to the dorsal scalp and ventral torso. Animals were designated to one of four treatment conditions: anodal tDCS (n=9), cathodal tDCS (n=8), positive control (no tDCS; n=6) and negative control (no PTZ, no tDCS; n=6). Immediately after PTZ injection, tDCS was initiated and continued for 120 minutes at 2 mA. Thereafter, animals were sacrificed for tissue collection. Hippocampal and neocortical tissues were analyzed separately by immunoblot. Actin was used to standardize consistency and protein loading. Results: (1) tDCS was well-tolerated by the rats who showed no over signs of injury or discomfort relative to positive control. (2) Constant current (± 5%) was reliably delivered through the saline/sponge electrodes which maintained their conductive properties for the 120-minute-long trials. (3) Relative to positive control, c-Fos expression was reduced in both neocortex (P < 0.05) and hippocampus (P < 0.04) by both anodal and cathodal tDCS. In both treatment conditions, the level of c-Fos expression approximated that of the negative control. Conclusions: tDCS applied acurtely during ongoing seizures appears to reduced c-Fos expression in the PTZ seizure rat pup. These results suggest that tDCS may reduce excessive neuronal activity, and this may in part contribute to its anticonvulsant effect. Equal suppression of c-Fos by anodal and cathodal tDCS was unexpected, as the effects of direct current stimulation are generally dependent on directionality, and clinically seen largely with cathodal tDCS. A potential mechanism may be due to uneven intracranial current distribution in the rat, and this will require further investivation. Improved understanding of the mechanism of the anticonvulsant effects of tDS may allow for further development as a clinical therapy of ongoing refractory seizures. (Supported by CIMIT, and NIH NINDS K08 NS055895)