Adenovirus-mediated expression of brain-derived neurotrophic factor protects spiral ganglion neurons from ototoxic damage

被引:83
作者
Nakaizumi, T [1 ]
Kawamoto, K [1 ]
Minoda, R [1 ]
Raphael, Y [1 ]
机构
[1] Univ Michigan, Dept Otolaryngol, KHRI, Ann Arbor, MI 48109 USA
关键词
adenovirus; spiral ganglion; brain-derived neurotrophic factor; ciliary-derived neurotrophic factor; gene therapy;
D O I
10.1159/000077264
中图分类号
R36 [病理学]; R76 [耳鼻咽喉科学];
学科分类号
100104 ; 100213 ;
摘要
Hair cell loss, the most common cause of deafness, is often associated with auditory nerve degeneration. Our goal was to determine the influence of combined ciliary-derived neurotrophic factor ( CNTF) and brain-derived neurotrophic factor ( BDNF) gene therapy on the survival of spiral ganglion neurons (SGNs) after elimination of inner hair cells in the mature guinea pig ear. Seven days after bilateral deafening, a 5-l suspension of CNTF and/ or BDNF adenovirus vectors was injected into the left scala tympani through the round window. Animals were sacrificed 28 days after deafening, and their inner ears were prepared for SGN counts. The SGN counts revealed that BDNF alone and the combined CNTF and BDNF treatment significantly enhanced SGN survival. CNTF did not significantly enhance the protective effect of BDNF. These data present possible strategies for enhancing SGN survival in cochlear implant procedures. Copyright (C) 2004 S. Karger AG, Basel.
引用
收藏
页码:135 / 143
页数:9
相关论文
共 87 条
[1]  
Agerman K, 1999, ANN NY ACAD SCI, V884, P131
[2]   HEARING, VOCALIZATION AND THE EXTERNAL EAR OF A MARSUPIAL, THE NORTHERN QUOLL, DASYURUS-HALLUCATUS [J].
AITKIN, LM ;
NELSON, JE ;
SHEPHERD, RK .
JOURNAL OF COMPARATIVE NEUROLOGY, 1994, 349 (03) :377-388
[3]   Role of STAT3 and Pl 3-Kinase/Akt in mediating the survival actions of cytokines on sensory neurons [J].
Alonzi, T ;
Middleton, G ;
Wyatt, S ;
Buchman, V ;
Betz, UAK ;
Müller, W ;
Musiani, P ;
Poli, V ;
Davies, AM .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2001, 18 (03) :270-282
[4]   Rescue and regrowth of sensory nerves following deafferentation by neurotrophic factors [J].
Altschuler, RA ;
Cho, Y ;
Ylikoski, J ;
Pirvola, U ;
Magal, E ;
Miller, JM .
OTOTOXICITY: BASIC SCIENCE AND CLINICAL APPLICATIONS, 1999, 884 :305-311
[5]   Gene therapy of human disease [J].
Balicki, D ;
Beutler, E .
MEDICINE, 2002, 81 (01) :69-86
[6]  
Baumgartner BJ, 1997, J NEUROSCI, V17, P6504
[7]   NEUROPOIETIC CYTOKINES IN THE HEMATOPOIETIC FOLD [J].
BAZAN, JF .
NEURON, 1991, 7 (02) :197-208
[8]   Neurotrophin-3 transduction attenuates cisplatin spiral ganglion neuron ototoxicity in the cochlea [J].
Bowers, WJ ;
Chen, XW ;
Guo, H ;
Frisina, DR ;
Federoff, HJ ;
Frisina, RD .
MOLECULAR THERAPY, 2002, 6 (01) :12-18
[9]   Programmed cell death in the developing nervous system [J].
Burek, MJ ;
Oppenheim, RW .
BRAIN PATHOLOGY, 1996, 6 (04) :427-446
[10]   Presymptomatic diagnosis of nonsyndromic hearing loss by genotyping [J].
Chen, AH ;
Mueller, RF ;
Prasad, SD ;
Greinwald, JH ;
Manaligod, J ;
Muilenburg, AC ;
Verhoeven, K ;
Van Camp, G ;
Smith, RJH .
ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY, 1998, 124 (01) :20-24