beta-Bungarotoxin application to the round window: an in vivo deafferentation model of the inner ear.
Hearing impairment can be caused by a primary lesion to the spiral ganglion neurons (SGNs) with the hair cells kept intact, for example via tumours, trauma or auditory neuropathy. To mimic these conditions in animal models various methods of inflicting damage to the inner ear have been used. However, only a few methods have a selective effect on the SGNs, which is of importance since it might be clinically more relevant to study hearing impairment with the hair cells undamaged. beta-Bungarotoxin is a venom of the Taiwan banded krait, which in vitro has been shown to induce apoptosis in neurons, leaving remaining cochlear cells intact. We wanted to create an in vivo rat model of selective damage to primary auditory neurons. Under deep anaesthesia, 41 rats received beta-Bungarotoxin or saline to the round window niche. At postoperative intervals between days 3 and 21 auditory brainstem response (ABR) measurement, immunohistochemistry, SGN quantification and cochlear surface preparation were performed. The results in the beta-Bungarotoxin-treated ears, as compared with sham-operated ears, show significantly increased ABR thresholds at all postoperative intervals, illustrating a severe to profound hearing loss at all tested frequencies (3.5, 7, 16 and 28 kHz). Quantification of the SGNs showed no obvious reduction in neuronal numbers until 14 days postoperatively. Between days 14 and 21 a significant reduction in SGN numbers was observed. Cochlear surface preparation and immunohistochemistry showed that the hair cells were intact. Our results illustrate that in vivo application of beta-Bungarotoxin to the round window niche is a feasible way of deafening rats by SGN reduction while the hair cells are kept intact.
Palmgren
Björn
B
Center for Hearing and Communication Research, Karolinska University Hospital, 171 76 Stockholm, Sweden. bjorn.palmgren@karolinska.se
Jin
Zhe
Z
Ma
Hongmin
H
Jiao
Yu
Y
Olivius
Petri
P
D000161:Acoustic Stimulation; D000344:Afferent Pathways / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis; D001309:Auditory Threshold; D002038:Bungarotoxins; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000294:innervation*; D016057:Evoked Potentials, Auditory, Brain Stem; D005240:Feasibility Studies; D005260:Female; D006198:Hair Cells, Auditory / Q000473:pathology; D034381:Hearing Loss / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012405:Round Window, Ear / Q000294:innervation*; D013136:Spiral Ganglion / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
D002038:Bungarotoxins