Journal of Shanghai Jiao Tong University (Medical Science) >

2022 , Vol. 42 >Issue 5: 583 - 590

DOI: https://doi.org/10.3969/j.issn.1674-8115.2022.05.005

Basic research

Establishment and evaluation of standardized steps for building a guinea pig model of auditory brainstem implantation

  • Xiang ZHOU ,
  • Jinxi PAN ,
  • Qinjie ZHANG ,
  • Yun LI ,
  • Ying CHEN ,
  • Haoyue TAN ,
  • Fei PENG ,
  • Sui HUANG ,
  • Zhiping TAN ,
  • Hao WU ,
  • Huan JIA
Expand
  • 1.Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
    2.Ear Institute, Shanghai Jiao Tong University School of Medicine; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200125, China
    3.Hearing Implantation Center, Shanghai Ninth People's Hospital, Shanghai 200125, China
    4.Nurotron Biotechnology Co. , Ltd. , Hangzhou 311100, China
JIA Huan, E-mail: huan.jia.orl@shsmu.edu.cn.

Received date: 2022-03-27

  Accepted date: 2022-04-15

  Online published: 2022-05-28

Supported by

National Natural Science Foundation of China(82000990);Shanghai Huangpu District Industrial Support Fund(XK2019015);Shanghai Talent Development Fund(2019047);Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases(14DZ2260300);Collaborative Innovation Project for Translational Medicine at Shanghai Jiao Tong University School of Medicine(TM202011)

Fold

Abstract

Objective

·To establish the guinea pig model of auditory brainstem implant (ABI) by modified transbulla-labyrinthine approach and assess its effectiveness and reliability.

Methods

·Twenty healthy adult male albino guinea pigs with normal hearing underwent ABI surgery via modified transbulla-labyrinthine approach. During the operation, the dorsal cochlear nucleus (DCN) of the brainstem was exposed laterally and implanted with a special ABI electrode array for guinea pigs. The evoked auditory brainstem response (eABR) was recorded from DCN and compared with the eABR waveform elicited from cochlear intraoperativly. After the electrode was implanted, the eABR waveform at DCN was recorded before euthanasia at 48 h, 7 d, 30 d and 180 d after operation. Then the brain tissue containing the electrode was harvested and the electrode neural-interface was evaluated by hematoxylin-eosin staining, immunofluorescence staining and q-PCR.

Results

·The eABR was successfully recorded at DCN from all animals during surgery, and the death occurred at 36 h to 48 h after operation. The waveform morphology of eABR at DCN was similar to that at cochlea. The latency of wave Ⅲ in eABR at DCN [ (0.84 ± 0.22)ms] was shorter than that of wave Ⅳ in EABR at cochlea (n=19), and the threshold difference between them was (0.11±0.14) mA (n=19). Compared with the intraoperative eABR at DCN, the average threshold increased by (0.10±0.10) mA (n=16), and the average delay of wave Ⅲ latency was (0.15±0.21) ms (n=16). Histological morphology analysis showed that the contact surface of cochlear nucleus around the electrode showed vacuolar changes at 48 h post-operation, and increased glial components were observed at the edge of DCN at 48 h, 7 d and 180 d post-operation. Results of q-PCR showed IL-1β and MMP9 were upregulated at 48 h and 7 d post-operation compared with the unimplanted electrode group, but there was no significant difference.

Conclusion

·The modeling success rate of established ABI-implanted guinea pig model is high and have outstanding repeativeness, and the local gliosis is preliminarily observed after implantation.

Key words： auditory brainstem implantation (ABI); animal model; guinea pig; auditory electrophysiology; histological morphology

Cite this article

Xiang ZHOU , Jinxi PAN , Qinjie ZHANG , Yun LI , Ying CHEN , Haoyue TAN , Fei PENG , Sui HUANG , Zhiping TAN , Hao WU , Huan JIA . Establishment and evaluation of standardized steps for building a guinea pig model of auditory brainstem implantation[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022 , 42(5) : 583 -590 . DOI: 10.3969/j.issn.1674-8115.2022.05.005

References

1 WROBEL C, ZAFEIRIOU M P, MOSER T. Understanding and treating paediatric hearing impairment[J]. EBioMedicine, 2021, 63: 103171.
2 WONG K, KOZIN E D, KANUMURI V V, et al. Auditory brainstem implants: recent progress and future perspectives[J]. Front Neurosci, 2019, 13: 10.
3 EVANS D G R. Neurofibromatosis type 2 (NF2): a clinical and molecular review[J]. Orphanet J Rare Dis, 2009, 4: 16.
4 PURAM S V, BARBER S R, KOZIN E D, et al. Outcomes following pediatric auditory brainstem implant surgery: early experiences in a North American center[J]. Otolaryngol Head Neck Surg, 2016, 155(1): 133-138.
5 NOIJ K S, KOZIN E D, SETHI R, et al. Systematic review of nontumor pediatric auditory brainstem implant outcomes[J]. Otolaryngol Head Neck Surg, 2015, 153(5): 739-750.
6 GUEX A A, HIGHT A E, NARASIMHAN S, et al. Auditory brainstem stimulation with a conformable microfabricated array elicits responses with tonotopically organized components[J]. Hear Res, 2019, 377: 339-352.
7 VACHICOURAS N, TARABICHI O, KANUMURI V V, et al. Microstructured thin-film electrode technology enables proof of concept of scalable, soft auditory brainstem implants[J]. Sci Transl Med, 2019, 11(514): eaax9487.
8 FERGUSON M, SHARMA D, ROSS D, et al. A critical review of microelectrode arrays and strategies for improving neural interfaces[J]. Adv Healthc Mater, 2019, 8(19): e1900558.
9 HITSELBERGER W E, HOUSE W F, EDGERTON B J, et al. Cochlear nucleus implants[J]. Otolaryngol Head Neck Surg, 1984, 92(1): 52-54.
10 RAUSCHECKER J P, SHANNON R V. Sending sound to the brain[J]. Science, 2002, 295(5557): 1025-1029.
11 MCCREERY D, HAN M, PIKOV V. Neuronal activity evoked in the inferior colliculus of the cat by surface macroelectrodes and penetrating microelectrodes implanted in the cochlear nucleus[J]. IEEE Trans Biomed Eng, 2010, 57(7): 1765-1773.
12 OTTO S R, SHANNON R V, WILKINSON E P, et al. Audiologic outcomes with the penetrating electrode auditory brainstem implant[J]. Otol Neurotol, 2008, 29(8): 1147-1154.
13 KOZIN E D, DARROW K N, HIGHT A E, et al. Direct visualization of the murine dorsal cochlear nucleus for optogenetic stimulation of the auditory pathway[J]. J Vis Exp, 2015(95): 52426.
14 CERVERA-PAZ F J, SALDA?A E, MANRIQUE M. A model for auditory brain stem implants: bilateral surgical deafferentation of the cochlear nuclei in the macaque monkey[J]. Ear Hear, 2007, 28(3): 424-433.
15 BAIZER J S, MANOHAR S, PAOLONE N A, et al. Understanding tinnitus: the dorsal cochlear nucleus, organization and plasticity[J]. Brain Res, 2012, 1485: 40-53.
16 LIU X, MCPHEE G, SELDON H L, et al. Acute study on the neuronal excitability of the cochlear nuclei of the Guinea pig following electrical stimulation[J]. Acta Otolaryngol, 1997, 117(3): 363-375.
17 EL-KASHLAN H K, NIPARKO J K, ALTSCHULER R A, et al. Direct electrical stimulation of the cochlear nucleus: surface vs. penetrating stimulation[J]. Otolaryngol Head Neck Surg, 1991, 105(4): 533-543.
18 HACKNEY C M, OSEN K K, KOLSTON J. Anatomy of the cochlear nuclear complex of Guinea pig[J]. Anat Embryol (Berl), 1990, 182(2): 123-149.
19 DUDáS B, MIHALY A, HANIN I. A ventral approach to stereotaxy of the Guinea pig brain[J]. J Neurosci Methods, 2000, 99(1/2): 79-83.
20 ODA K, KAWASE T, YAMAUCHI D, et al. Electrophysiological mapping of the cochlear nucleus with multi-channel bipolar surface microelectrodes[J]. Eur Arch Otorhinolaryngol, 2013, 270(3): 869-874.
21 HUANG C Q, SHEPHERD R K. Reduction in excitability of the auditory nerve following electrical stimulation at high stimulus rates: v. Effects of electrode surface area[J]. Hear Res, 2000, 146(1/2): 57-71.
22 ODA K, KAWASE T, YAMAUCHI D, et al. Electrophysiological mapping of the cochlear nucleus with multi-channel bipolar surface microelectrodes[J]. Eur Arch Otorhinolaryngol, 2013, 270(3): 869-874.
23 GOLABCHI A, WOEPPEL K M, LI X, et al. Neuroadhesive protein coating improves the chronic performance of neuroelectronics in mouse brain[J]. Biosens Bioelectron, 2020, 155: 112096.
24 GOLABCHI A, WU B C, LI X, et al. Melatonin improves quality and longevity of chronic neural recording[J]. Biomaterials, 2018, 180: 225-239.
25 JORFI M, SKOUSEN J L, WEDER C, et al. Progress towards biocompatible intracortical microelectrodes for neural interfacing applications[J]. J Neural Eng, 2015, 12(1): 011001.
26 KOZAI T D, JAQUINS-GERSTL A S, VAZQUEZ A L, et al. Brain tissue responses to neural implants impact signal sensitivity and intervention strategies[J]. ACS Chem Neurosci, 2015, 6(1): 48-67.
27 WELLMAN S M, ELES J R, LUDWIG K A, et al. A materials roadmap to functional neural interface design[J]. Adv Funct Mater, 2018, 28(12): 1701269.
28 MCGINN M D, FADDIS B T. Exposure to low frequency noise during rearing induces spongiform lesions in gerbil cochlear nucleus: high frequency exposure does not[J]. Hear Res, 1994, 81(1/2): 57-65.
29 REMPE R G, HARTZ A M S, SOLDNER E L B, et al. Matrix metalloproteinase-mediated blood-brain barrier dysfunction in epilepsy[J]. J Neurosci, 2018, 38(18): 4301-4315.
30 GUEX A A, VACHICOURAS N, HIGHT A E, et al. Conducting polymer electrodes for auditory brainstem implants[J]. J Mater Chem B, 2015, 3(25): 5021-5027.
Options
Outlines

/

〈 〉