| Objectives:The aim of the present study was to evaluate the effects of Dexamethasone and Healon on tissue response, hearing preservation and presence of pro-inflammatory factors (TGF-, TNF, IL-17A) in blood following cochlear implantation in animal model (Cat).Methods and Materials:The present experiment was divided into long-term and short-term study group.Short-term study:13cats were chosen for this study. It was subdivided into five groups. All groups were unilaterally implanted with MED EL IE except group5(Round window incision only). Contralateral ears were not operated. Group1(n=3) was implanted with electrode only (E). Group2(n=3) were implanted with Electrode+Healon (E+H). Group3(n=3) was implanted with Electrode+Dexamethasone (E+H). Group4(n=3) was implanted with Electrode+Healon+Dexamethasone (E+H+DX). Group5(n=2) had just round window incised without implanted electrode.Blood taken before operation was a control blood in all groups. According to group, blood was taken before operation and at0,1,3,7and14-day respectively after operation. Simultaneous measurement of three pro-inflammatory factors (TGF-β, T NF-α, and IL-17A) in a single sample of serum using ELISA (Sandwich type) was done. Statistical analysis was performed using repeated analysis of variance (ANOVA), mixed procedure, and chi-square test. REML (Restricted, reduced maximum likelihood) was adapted as an estimation method. Results were considered statistically significant when P<0.05. All data analyses were performed by work.data2as a data set model. ABR thresholds were recorded before operation and at0,1,3,7, and14days after operation respectively. Pair t-tests were used for comparing means of ABR thresholds. A p value<0.05was considered as significant. Finally one cochlea from each of3,7,14day group (n=4) were undergone histo-pathological assessment.Long-term study:11cats (22cochlea) were chosen for long-term study. It was subdivided into five groups. Cats were implanted bilaterally with two different types of electrode design (Med EL IE and Nurotron CI). Each cat (10Cochlea) was implanted unilaterally with MED-EL IE. Of10contralateral cochleas,5were implanted with Nurotron in house test device without internal part and5with Nurotron cochlear implant internal part (CS-10A). Group1(n=2) was implanted with electrode only (E) keeping contralateral cochlea (n=2) normal (not operated). Group2(n=6) were implanted with Electrode+Healon (E+H). Group3(n=6) was implanted with Electrode+Dexamethasone (E+DX). Group4(n=6) was implanted with Electrode+Healon+Dexamethasone (E+H+DX).ABR thresholds were recorded before operation, and at one week and3months after operation. Pair t-tests were used for comparing means of ABR thresholds. A p value<0.05was considered as significant.EABR recording was done on five cats (5cochlea) after one month of continuous electrical stimulation. Chronic electrical stimulation commenced after two month of cochlear implantation. Of5cats,2were normal hearing adult cats and3were deafened cats. Two cats were from E+H group, two from E+DX group and one from E+H+DX group.At the end of3months after cochlear implantation, all cochleae (n=22) were undergone histo-pathological assessment. Results:1. ELISA (Enzyme-linked Immune-Sorbent Assay) Based on results, it is concluded that cochlear implant surgery doesn’t increase pro-inflammatory cytokine and chemokine level in blood (TGF-β, TNF-α, IL-17A). It signifies no inflammation at peripheral level after cochlear implant surgery.Ⅱ. ABR (Auditory Brainstem Response) Based on this experiment it is concluded that hearing can be recovered (partial or complete) in animal treated with either Healon, Dexamethasone or combined Healon+Dexamethasone than electrode insertion only in all groups. Maximum recovery of hearing can be recorded in animal treated with combined Healon and Dexamethasone (E+H+DX) than either of the groups.Recovery of hearing for lower frequency is higher (even complete) than higher frequency (4to8KHz). It indicated that the most extensive hearing loss occurred in the high-frequency region of the cochlea (4-8KHz), adjacent to the stimulating electrode and typically extended to the8and6KHz regions. Progressive recovery of hearing was recorded in all groups except electrode only group. Highest recovery of hearing (both lower and high frequency) was recorded in animals treated with E+H+DX.The absence of significant differences in animal treated with E+H+DX ears in response to click and0.5to8kHz tones demonstrates the combined dexamethasone and Healon is effective in conserving hearing during cochlear implantation. This results of infusion of combined Healon and Dexamethasone in animal model of cochlear implant could be a novel therapeutic strategy for preventing of progressive hearing loss that results from cochlear implant related consequences.Ⅲ. EABR (Electrically Evoked Auditory Brainstem Response) Of24E of Nurotron CS-10A, EABR waves were obtained from a total of22E,8E and18E in C12, C8, and C4respectively. But EABR waves were not recorded in two cats (deaf) with extruded electrodes out of the scala tympani even though they are still found inside bulla cavity (found near to promontory). In this present study the morphology and characteristic of wave recorded is different in all three cats. Waves Ⅲ and Ⅴ were recorded in cat12and4(C12and C4). Only V wave was recorded in cat8(C8).The amplitude of the wave Ⅲ was larger, more robust in normal hearing cat (cat12) than hearing-impaired cat (cat4). But the amplitude of wave V was large, more prominent in impaired cat (cat4) than normal hearing cat (cat12). Bases on these observations, we concluded that the EABR demonstrated differences in the way normal and impaired systems respond to electrical stimulation.The amplitude was decreasing from E1to E24in Cat12,4(C12, C4). It also required higher current level as it moves from E1to E24. As the intensity of the stimulus decrease the latency of each wave increases. Wave Ⅴ latency (Cat4) was progressively increasing from El to E20(Apical to Basal)(chart3). Wave Ⅲ latency (Cat12) was significantly longer for E20(Basal) compared with E10(Middle) or E1(Apical). So for normal hearing cats, latencies of wave Ⅲ and Ⅴ were found to increase than deaf cat.Although EABR to electrical stimulation of auditory nerve techniques have been developed in the last two decades and are still controversial subjects of debate in the field of cochlear implant assessment. The waveform recorded in the present study could not confirm its origin. Based on these results obtained in the present study it is again doubtful about EABR functioning as a measure of subsequent activation of the auditory pathway and spiral ganglion cell survival.IV. COCHLEA HISTOPATHOLOGY: As fibrotic changes were seen in all groups (E only, E+H, E+DX, E+H+DX) in the present study, it indicates that a single intracochlear application of Healon, Dexamethasone, or combination of Healon and Dexamethasone does not reduce the growth of fibrous tissue within scala tympani.Neither Healon nor Dexamethasone suppressed tissue growth significantly, nor was they’re a significant correlation between the amount of tissue within the cochlea and hearing loss. CONCLUSIONS:(1) Based on these results, it is concluded that ’cochlear implant surgery doesn’t increase pro-inflammatory cytokine and chemokine level in blood (TGF-β, TNF-α, and IL-17A). It signifies no inflammation at peripheral level after cochlear implant surgery.(2) Hearing can be recovered (partial or complete) in animal treated with either Healon, Dexamethasone or combined Healon+Dexamethasone than electrode insertion only. Maximum recovery of hearing (both lower and high frequency) can be recorded in animal treated with combined Healon and Dexamethasone (E+H+DX) than either of the groups.(3) The morphology and characteristic of the EABR wave III and V recorded is different in the normal hearing and impaired cat.(4) As fibrotic changes were seen in all groups (E only, E+H, E+DX, E+H+DX) in the present study, it indicates that Neither Healon nor Dexamethasone suppressed tissue growth significantly, nor was they’re a significant correlation between the amount of tissue within the cochlea and hearing loss. |
PDF Full Text Request