Abstract
Because of vast variability of cochlear implantation outcomes in prelingual deafness treatment, identification of good and poor performers remains a challenging task. To address this issue, we investigated genetic variants of matrix metalloproteinase 9 (MMP9) and brain-derived neurotrophic factor (BDNF) and plasma levels of MMP-9, BDNF, and pro-BDNF that have all been implicated in neuroplasticity after sensory deprivation in the auditory pathway. We recruited a cohort of prelingually deaf children, all implanted before the age of 2, and carried out a prospective observation (N = 61). Next, we analyzed the association between (i) functional MMP9 (rs20544, rs3918242, rs2234681) and BDNF (rs6265) gene variants (and their respective protein levels) and (ii) the child’s auditory development as measured with the LittlEARS Questionnaire (LEAQ) before cochlear implant (CI) activation and at 8 and 18 months post-CI activation. Statistical analyses revealed that the plasma level of MMP-9 measured at implantation in prelingually deaf children was significantly correlated with the LEAQ score 18 months after CI activation. In the subgroup of DFNB1-related deafness (N = 40), rs3918242 of MMP9 was significantly associated with LEAQ score at 18 months after CI activation; also, according to a multiple regression model, the ratio of plasma levels of pro-BDNF/BDNF measured at implantation was a significant predictor of overall LEAQ score at follow-up. In the subgroup with DFNB1-related deafness, who had CI activation after 1 year old (N = 22), a multiple regression model showed that rs3918242 of MMP9 was a significant predictor of overall LEAQ score at follow-up.
Highlights
Congenital Deafness Treatment with Cochlear Implantation and Variability of Its OutcomeCongenital deafness is a disabling condition which, untreated, has far-reaching consequences and profoundly affects the quality of the patient’s life
LittlEARS Questionnaire (LEAQ) scores measured at different time intervals from cochlear implant (CI) activation and brain-derived neurotrophic factor (BDNF), matrix metalloproteinases (MMPs)-9 levels, and pro-BDNF/BDNF ratios measured at CI activation were tested for correlation and strength using a Pearson test or a Spearman test
Our main findings can be summarized as follows. (i) Plasma level of MMP-9 protein measured at cochlear implantation in congenitally deaf children is significantly correlated with auditory development measurements (LEAQ score) at 18 months after the device activation. (ii) In the subgroup with DFNB1-related deafness, functional matrix metalloproteinase 9 (MMP9) variant rs3918242 significantly impacts auditory development measured at the 1 8th month after the device activation; it is a significant predictor of overall LEAQ score in the subgroup with DFNB1-related deafness and activation after at the 1 year. (iii) The proBDNF/BDNF ratio measured at cochlear implantation is a significant predictor of auditory development (LEAQ score) as measured in the subgroup with DFNB1-related deafness
Summary
Congenital Deafness Treatment with Cochlear Implantation and Variability of Its Outcome. Delivery of electrical stimulation to the auditory pathway involves an interplay between implant software and brain tissue (wetware) [1, 4] For this reason, it is thought that the missing factors contributing to CI outcome, which might serve as either biochemical or genetic biomarkers of auditory development following a CI, could be located in the biological environment of the implant [4]. It is thought that the missing factors contributing to CI outcome, which might serve as either biochemical or genetic biomarkers of auditory development following a CI, could be located in the biological environment of the implant [4] Finding such biomarkers would be important, as it would allow increased efforts to be made in identifying children at risk of failure of their CI. We have searched for associations among plasma levels of MMP-9, BDNF collected at cochlear implantation, and pro-BDNF/BDNF ratio and the children’s auditory development
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