Reduced spiral ganglion neuronal loss by adjunctive neurotrophin-3 in experimental pneumococcal meningitis

被引:24
作者
Demel, Cornelia [1 ]
Hoegen, Tobias [1 ]
Giese, Armin [2 ]
Angele, Barbara [1 ]
Pfister, Hans-Walter [1 ]
Koedel, Uwe [1 ]
Klein, Matthias [1 ]
机构
[1] Univ Munich, Dept Neurol, Klinikum Grosshadern, D-81377 Munich, Germany
[2] Univ Munich, Ctr Neuropathol & Prion Res, D-81377 Munich, Germany
来源
JOURNAL OF NEUROINFLAMMATION | 2011年 / 8卷
关键词
SENSORINEURAL HEARING-LOSS; NERVE GROWTH-FACTOR; BACTERIAL-MENINGITIS; MENINGOGENIC LABYRINTHITIS; COCHLEAR IMPLANTATION; BARRIER DISRUPTION; AUDITORY NEURONS; GUINEA-PIGS; SURVIVAL; DAMAGE;
D O I
10.1186/1742-2094-8-7
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: Hearing loss is a frequent long-term complication of pneumococcal meningitis (PM). Its main pathological correlate is damage to the organ of Corti and loss of spiral ganglion neurons. The only current treatment option is cochlear implants which require surviving neurons. Here, we investigated the impact of systemically applied neurotrophin-3 (NT-3) on long-term hearing loss and the survival of neurons. Methods: Eighteen hours after infection with S. pneumoniae, C57BL/6 mice were treated with a combination of ceftriaxone with NT-3 or dexamethasone or placebo. Hearing, cochlear damage, and brain damage were assessed by audiometry and histology. Results: The main findings from immunohistochemical visualization of neurotrophins (NT-3, BDNF) and their receptors (TrkB, TrkC, and p75) in the cochlea were (i) enhanced staining for the cell survival-promoting receptor TrkB and (ii) increased NT-3 staining in NT-3 treated mice, showing that systemically applied NT-3 reaches the cochlea. The major effects of adjunctive NT-3 treatment were (i) a reduction of meningitis-induced hearing impairment and (ii) a reduction of spiral ganglion neuronal loss. The efficacy of NT-3 therapy was comparable to that of dexamethasone. Conclusion: Systemically applied NT-3 might be an interesting candidate to improve hearing outcome after pneumococcal meningitis.
引用
收藏
页数:12
相关论文
共 56 条
[31]  
Merchant SN, 1996, AM J OTOL, V17, P375
[32]   Neurotrophins can enhance spiral ganglion cell survival after inner hair cell loss [J].
Miller, JM ;
Chi, DH ;
OKeeffe, LJ ;
Kruszka, P ;
Raphael, Y ;
Altschuler, RA .
INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 1997, 15 (4-5) :631-643
[34]   HISTOPATHOLOGIC CORRELATION OF SPIRAL GANGLION-CELL COUNT AND NEW BONE-FORMATION IN THE COCHLEA FOLLOWING MENINGOGENIC LABYRINTHITIS AND DEAFNESS [J].
NADOL, JB ;
HSU, WC .
ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 1991, 100 (09) :712-716
[35]   SURVIVAL OF SPIRAL GANGLION-CELLS IN PROFOUND SENSORINEURAL HEARING-LOSS - IMPLICATIONS FOR COCHLEAR IMPLANTATION [J].
NADOL, JB ;
YOUNG, YS ;
GLYNN, RJ .
ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 1989, 98 (06) :411-416
[36]   Axonal injury, a neglected cause of CNS damage in bacterial meningitis [J].
Nau, R ;
Gerber, J ;
Bunkowski, S ;
Brück, W .
NEUROLOGY, 2004, 62 (03) :509-511
[37]   Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss [J].
Noben-Trauth, K ;
Zheng, QY ;
Johnson, KR .
NATURE GENETICS, 2003, 35 (01) :21-23
[38]   Matrix metalloproteinases contribute to the blood-brain barrier disruption during bacterial meningitis [J].
Paul, R ;
Lorenzl, S ;
Koedel, U ;
Sporer, B ;
Vogel, U ;
Frosch, M ;
Pfister, HW .
ANNALS OF NEUROLOGY, 1998, 44 (04) :592-600
[39]   Schwann cells genetically modified to express neurotrophins promote spiral ganglion neuron survival in vitro [J].
Pettingill, L. N. ;
Minter, R. L. ;
Shepherd, R. K. .
NEUROSCIENCE, 2008, 152 (03) :821-828
[40]   Working memory in deaf children with cochlear implants: Correlations between digit span and measures of spoken language processing [J].
Pisoni, DB ;
Geers, AE .
ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 2000, 109 (12) :92-93