Effects of Chronic Electrical Stimulation on Spiral Ganglion Neuron Survival and Size in Deafened Kittens

Abstract

We have studied spiral ganglion cell (SGC) survival and soma size in neonatally pharmacologically deafened kittens. They were implanted with a four-electrode array in the left cochlea at 100 to 180 or more days of age. Eight animals were chronically stimulated approximately 1000 hours over approximately 60 days with charge-balanced, biphasic current pulses; three were unstimulated controls. Using three-dimensional computer-aided reconstruction of the cochlea, the SGC position and cross-sectional area were stored. SGC position was mapped to the organ of Corti by perpendicular projections, starting from the basal end. The basal region of the cochlea was divided into three 4-mm segments. SGC survival (number per 0.1 mm of the length of the organ of Corti) and soma size for stimulated cochleae were compared statistically with implanted but unstimulated cochleae. There was no evidence of an effect of electrical stimulation on SGC survival under this protocol and with this duration. On the other hand, the cell size on the stimulated side was significantly larger than the control side in the middle segment (4 to 8 mm from the basal end). SGCs undergo a reduction in size after prolonged auditory deprivation; however, these changes may be partially moderated after chronic intracochlear electrical stimulation.

Combining Cell-Based Therapies and Neural Prostheses to Promote Neural Survival

“…There was no significant effect of chronic ES alone on SGN survival, a finding consistent with previous studies in the cat [27,31,32] and guinea pig [8,33,34], although this is not a uniform finding [25,[35][36][37][38][39][40][41]. Differences in the methodology (e.g., the duration and severity of deafness, the age at deafness onset, electrode design and position, duration, and mode of chronic ES) complicate direct The mean (± SEM) of peripheral process packing density expressed as a percentage of the OSL.…”

Effects of Brain-Derived Neurotrophic Factor (BDNF) and Electrical Stimulation on Survival and Function of Cochlear Spiral Ganglion Neurons in Deafened, Developing Cats

“…Profound deafness has been reported to result in reduction in the size of SG neuron perikarya in many previous studies and in various deaf animal models (Agterberg et al 2008(Agterberg et al , 2009Araki et al 1998;Elverland and Mair 1980;Glueckert et al 2008;Leake et al 1999Leake et al , 2007Leake et al , 2011; Leake and Hradek 1988;McGuinness and Shepherd 2005;Shepherd et al 2005;Wise et al 2005). Presumably, reduction in somatic size reflects reduced metabolic requirements of these neurons due to reduced spike activity after deafness (Hartmann et al 1984;Liberman and Kiang 1978;Shepherd and Javel 1997).…”

“…Presumably, reduction in somatic size reflects reduced metabolic requirements of these neurons due to reduced spike activity after deafness (Hartmann et al 1984;Liberman and Kiang 1978;Shepherd and Javel 1997). When electrical stimulation from a CI is applied to reactivate these neurons, modest but significant increases in SG soma area in the stimulated cochleae have been reported (Araki et al 1998;Coco et al 2007;Leake et al 1999Leake et al , 2007. However, the effects on soma area associated with neurotrophin administration are much greater than the cell size changes elicited with electrical stimulation.…”

“…In our laboratory, studies of cats deafened prior to hearing onset have shown that multichannel CI electrical stimulation applied over several months results in substantial improvement in SG neural survival (Leake et al 1999(Leake et al , 2007(Leake et al , 2008a above that seen in the contralateral deafened cochleae. Other studies, however, have not found evidence of trophic effects of electrical stimulation (Araki et al 1998;Coco et al 2007;Li et al 1999;Shepherd et al 1994). These disparities in findings suggest that differences among animal models, methods of stimulation (e.g., the position of stimulating electrodes, applied signals, and efficacy in exciting neurons across a broad sector of the spiral ganglion), and/or methods of analysis of SG density are critically important.…”

Factors influencing neurotrophic effects of electrical stimulation in the deafened developing auditory system

“…Lousteau (1987), Hartshorn et al (1991), and Miller and Altschuler et al (1995; demonstrated increased SG cell survival after chronic ICES in guinea pigs deafened by ototoxic drugs and implanted as young adults. In contrast, other studies have failed to find trophic effects in vivo in guinea pigs , and Shepherd and coworkers (Araki et al, 1998;Shepherd et al, 1994) found no overall difference in SG cell survival after chronic ICES in cats deafened at an early age by ototoxic drugs, although recently they reported a significant regional increase in SG survival in partially deafened cats and a consistent increase in the size of stimulated SG cells (Coco et al, 2007).…”