Does exogenous GM1 ganglioside enhance the effects of electrical stimulation in ameliorating degeneration after neonatal deafness?

This study examined the combined effects of administration of exogenous GM1 ganglioside and electrical stimulation on the cochlear nucleus (CN) of cat s deafened neonatally by ototoxic drugs. Five normal hearing adult cats ser ved as controls. Another 12 cats were deafened bilaterally by daily injecti ons of neomycin sulfate (60 mg/kg) for 17-21 days after birth until auditor y brainstem testing demonstrated profound hearing loss. Six of the deaf ani mals comprised the GM1 group, which received daily injections of GM1 gangli oside (30 mg/kg) for 28 38 days during the period after profound deafness w as confirmed, and prior to receiving a cochlear implant. The non-GM1 group (n=6) received no treatment during this interim period. All the deafened an imals underwent unilateral cochlear implantation at 6 -9 weeks postnatal an d received several months (mean duration, 32 weeks) of chronic electrical s timulation (4 h/day, 5 days/week). Stimulation was delivered by intracochle ar bipolar electrodes, using electrical signals that were designed to be te mporally challenging to the central auditory system. Results showed that in the neonatally deafened animals, both the GM1 and non-GM1 groups, the volu me of the CN was markedly reduced (to 76% of normal), but there was no diff erence between the animals that received GM1 and those that did not. The cr oss sectional areas of spherical cell somata in both GM1 and non-GM1 groups also showed a highly significant reduction in size, to less than or equal to 75% of normal after neonatal deafening. Moreover, in both the GM1 and no n-GM1 groups, the spherical cells in the CN ipsilateral to the implanted co chlea were significantly larger (6%) than cells in the control, unstimulate d CN. Again, however, there was no significant difference between the GM1 g roup and the non-GM1 group in spherical cell size. These results contrast s harply with previous reports that exogenous GM1 prevents CN degeneration af ter neonatal conductive hearing loss and partially prevents spiral ganglion cell degeneration when administered immediately after ototoxic drug deafen ing in adult animals. Taken together, findings to date suggest that GM1 may be effective in preventing degeneration only if the GM1 is administered im mediately at the time hearing loss occurs. (C)) 2001 Elsevier Science B.V. All rights reserved.