Delayed electrical stimulation and BDNF application following induced deafness in rats.
CONCLUSIONS
Under the condition of delayed intervention (30 days after deafening) following gentamicin+furosemide deafening in rats, we conclude that chronic intracochlear electrical stimulation (ES) and continuous intracochlear administration of brain-derived neurotrophic factor (BDNF) enhance spiral ganglion cell (SGC) body and peripheral process survival and improve auditory sensitivity. Moreover, the combination of ES and BDNF has a synergistic protective effect rather than an additive effect. Both SGC body and peripheral process influence the auditory sensitivity, and the latter appears to be more important.


OBJECTIVE
To determine the influence of delayed application of combined ES and neurotrophins on the survival of SGC body and peripheral processes after induced deafness in the rat. This study also explored the relationship between auditory sensitivity and SGC/peripheral process density.


METHODS
The left cochlea of profoundly deafened rats was implanted with an electrode and drug-delivery system 30 days after deafening. BDNF or artificial perilymph (AP) was delivered continuously for 28 days. Experimental animals received ES with or without BDNF (BDNF+ES and ES+AP), and control animals received BDNF or AP without ES (BDNF and AP). The right cochleae of the animals served as deafened untreated controls. Electrically evoked auditory brainstem responses (EABRs) were recorded immediately after surgery and every 7 days.


RESULTS
In the AP group, EABR thresholds demonstrated a systematic and rapid increase throughout the treatment period after the deafening procedure and electrode implantation. However, in the other three treatment groups, EABR thresholds showed a slow increase at the beginning and then slow decrease. The thresholds of the BDNF and ES+AP groups were significantly less than those of the AP group from day 7 to 28 and those of the BDNF+ES group were significantly less than those of other three groups from day 21 to 28, indicating that BDNF infusion and chronic ES have a synergistic effect rather than an additive effect. In terms of SGC and peripheral process density, the difference between the treated and control ears of BDNF, ES+AP, and BDNF+ES groups was clearly significant. Analysis of the SGC/peripheral process density of the left cochlea across the treatment groups demonstrated that SGC/peripheral process density of the BDNF and ES+AP groups was significantly greater than that of the AP group and the density of the BDNF+ES group was significantly greater than that of the other three groups, indicating that BDNF infusion and chronic ES have a synergistic effect rather than an additive effect. Finally, a functional formula was developed relating the last EABR threshold and SGC density and process density.
Song
Bing-Nan
BN
Department of Otorhinolaryngology, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China.
Li
Yong-Xin
YX
Han
De-Min
DM
D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D003131:Combined Modality Therapy; D003638:Deafness / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects* / Q000502:physiology; D005665:Furosemide / Q000633:toxicity*; D005839:Gentamicins / Q000633:toxicity*; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012533:Scala Tympani / Q000187:drug effects / Q000503:physiopathology; D013136:Spiral Ganglion / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
D019208:Brain-Derived Neurotrophic Factor; D005839:Gentamicins; D005665:Furosemide