Effect of cochlear implantation on residual spiral ganglion cell count as determined by comparison with the contralateral nonimplanted inner ear in humans.
ABSTRACT It is generally assumed that at least a minimal number of spiral ganglion cells is essential for successful speech perception with a cochlear implant. Although the insertion of a multichannel cochlear implant frequently results in loss of residual hearing in the implanted ear, this outcome does not imply that significant damage to residual populations of spiral ganglion cells has occurred. The purpose of the current study was to compare spiral ganglion cell counts in implanted and nonimplanted cochleas in 11 patients for whom both temporal bones were available and in whom a multichannel cochlear implant had been placed unilaterally. The temporal bones were processed for light microscopy by standard techniques. The cochleas were reconstructed by 2-dimensional methods. Spiral ganglion cell counts of the implanted and nonimplanted sides were compared by a paired t-test (2-tailed). The mean spiral ganglion cell counts for implanted and nonimplanted ears were not statistically different in the most basal three segments of the cochlea. However, the mean spiral ganglion cell count in segment 4 (apical segment) and the mean total spiral ganglion cell count were lower in the implanted cochleas than in the nonimplanted cochleas (p < .01). The results of this study suggest a modest decrease in the total spiral ganglion cell count in the implanted ears as compared to the nonimplanted ears, principally in the apical segment. Possible interpretations of this finding are discussed.
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ABSTRACT: The spiral ganglion cell (SGC) is the target of electrical stimulation in cochlear implants. This study is designed to test the hypothesis that chronic electrical stimulation tends to preserve SGCs in implanted hearing-impaired ears. A total of 26 pairs of temporal bones were studied from 26 individuals who in life suffered bilateral profound hearing impairment that was symmetric (in degree of impairment and etiology) across ears and then underwent unilateral cochlear implantation. The subjects were divided in two groups by stimulus configuration: bipolar (n=16) or monopolar (n=10). The temporal bones were prepared for histological review by standard methods and two measures of SGC status were made by cochlear segment: count and maximal cross-sectional area. Within-subject comparison of the measures between the implanted-stimulated and the unimplanted ears showed: (1) for both stimulus configurations, the mean (across subjects and segments) of the count difference (implanted ear - unimplanted ear) was significantly less than zero; (2) the mean (across subject) count difference for cochlear segments I, II and III (segments with electrode contacts in the implanted ear) was significantly less negative than the mean difference for cochlear segment IV (no electrode in implanted ear) for bipolar but not for monopolar stimulation; (3) neither implantation-stimulation nor stimulus configuration significantly influenced the measures of maximum cross-sectional cell area. The SGC count results are consistent with the hypothesis that implantation results in a propensity across the whole cochlea for SGCs to degenerate and with chronic bipolar stimulation ameliorating this propensity in those cochlear segments with electrodes present.Hearing research 05/2013; 302. DOI:10.1016/j.heares.2013.04.007 · 2.85 Impact Factor
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ABSTRACT: Regrowth of peripheral spiral ganglion neuron (SGN) fibers is a primary objective in efforts to improve cochlear implant outcomes and to potentially reinnervate regenerated hair cells. Cyclic adenosine monophosphate (cAMP) regulates neurite growth and guidance via activation of protein kinase A (PKA) and Exchange Protein directly Activated by Cylic AMP (Epac). Here we explored the effects of cAMP signaling on SGN neurite length in vitro. We find that the cAMP analog, cpt-cAMP, exerts a biphasic effect on neurite length; increasing length at lower concentrations and reducing length at higher concentrations. This biphasic response occurs in cultures plated on laminin, fibronectin, or tenascin C suggesting that it is not substrate dependent. cpt-cAMP also reduces SGN neurite branching. The Epac-specific agonist, 8-pCPT-2'-O-Me-cAMP, does not alter SGN neurite length. Constitutively active PKA isoforms strongly inhibit SGN neurite length similar to higher levels of cAMP. Chronic membrane depolarization activates PKA in SGNs and also inhibits SGN neurite length. However, inhibition of PKA fails to rescue neurite length in depolarized cultures implying that activation of PKA is not necessary for the inhibition of SGN neurite length by chronic depolarization. Expression of constitutively active phosphatidylinositol 3-kinase, but not c-Jun N-terminal kinase, isoforms partially rescues SGN neurite length in the presence of activated PKA. Taken together, these results suggest that activation of cAMP/PKA represents a potential strategy to enhance SGN fiber elongation following deafness; however such therapies will likely require careful titration so as to promote rather than inhibit nerve fiber regeneration.Hearing research 12/2011; 283(1-2):33-44. DOI:10.1016/j.heares.2011.11.010 · 2.85 Impact Factor
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ABSTRACT: This study is designed to measure the degree to which spiral ganglion cell (SGC) survival in the left and right ears is similar in profoundly hearing-impaired human patients with symmetric (right/left) etiology and sensitivity. This is of interest because a small difference between ears would imply that one ear could be used as a control ear in temporal bone studies evaluating the impact on SGC survival of a medical intervention in the other ear. Forty-two temporal bones from 21 individuals with bilaterally symmetric profound hearing impairment were studied. Both ears in each individual were impaired by the same etiology. Rosenthal's canal was reconstructed in two dimensions and segmental and total SGCs were counted. Correlation analysis and t-tests were used to compare segmental and total counts of left and right ears. Statistical power calculations illustrate how the results can be used to estimate the effect size (right/left difference in SGC count) that can be reliably identified as a function of sample size. Left counts (segmental and total) were significantly correlated with those in the right ears (p < 0.01) and the coefficients of determination for segments 1 to 4 and total count were respectively 0.64, 0.91, 0.93, 0.91 and 0.98. The hypothesis that mean segmental and total counts of right and left are the same could not be rejected by paired t-test. The variance in the between-ear difference across the temporal bones studied indicates that useful effect sizes can be reliably identified using subject numbers that are practical for temporal bone studies. For instance, there is 95% likelihood that an interaural difference in SGC count of approximately 1000 cells associated with a treatment/manipulation of one ear will be reliably detected in a bilaterally-symmetric profound hearing loss population of temporal bones from approximately 10 subjects.Hearing research 12/2011; 282(1-2):56-62. DOI:10.1016/j.heares.2011.10.002 · 2.85 Impact Factor