Dose-response study of the pathological effects of chronically applied direct current stimulation on the normal rat...

Electrical stimulation of the mammalian central nervous system (CNS) can result in extensive destruction of tissue unless applied within specific stimulation parameters. Classically, unbalanced or monopolar currents have been avoided in order to minimize these harmful effects. However, direct current (DC) fields have recently been proposed for the treatment of spinal cord injury. Until now, no rigorous analysis has been made of the safety of these fields in the mammalian CNS. The purpose of this study was to determine the amount of chronically applied DC current that can be tolerated by the normal rodent spinal cord stimulated with metal disc electrodes. Thirty-five normal rats underwent implantation of DC stimulating devices and were allowed to recover for a period of 2 to 12 weeks. The stimulators delivered constant currents of 0 to 50 microA through two disc-shaped platinum/iridium electrodes positioned extradurally at the C-7 and T-3 levels. Following sacrifice of the animals, serial 8-microns cross sections of the spinal cord at the electrode sites were examined microscopically. Evidence of demyelination presumed due to the physical presence of the rostral electrode was seen in animals from most groups including control animals. Pathological changes directly attributable to the applied fields were seen with current as low as 3 microA. It was concluded that DC's of 3 microA or more are harmful to the mammalian CNS with this method of stimulation. In addition, the data suggest that the maximum current density tolerated by the rodent spinal cord is in the order of 75 microA/sq cm. These findings have important implications for the use of chronic DC stimulation in the mammalian CNS.