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


CONCLUSIONS
Systemically applied NT-3 might be an interesting candidate to improve hearing outcome after pneumococcal meningitis.
Department of Neurology, Klinikum Grosshadern, Ludwig Maximilians University Munich, Marchioninistrasse 15, 81377 Munich, Germany.
Cornelia
C
Demel
Tobias
T
Hoegen
Armin
A
Giese
Barbara
B
Angele
Hans-Walter
HW
Pfister
Uwe
U
Koedel
Matthias
M
Klein
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002443:Ceftriaxone / Q000009:adverse effects / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000033:anatomy & histology; D003051:Cochlea / Q000187:drug effects / Q000473:pathology; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use; D004195:Disease Models, Animal; D034381:Hearing Loss / Q000209:etiology / Q000517:prevention & control; D006624:Hippocampus / Q000033:anatomy & histology; D006801:Humans; D008586:Meningitis, Pneumococcal / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D020933:Neurotrophin 3 / Q000627:therapeutic use*; D010919:Placebos; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D013136:Spiral Ganglion / Q000166:cytology / Q000187:drug effects / Q000473:pathology*
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D010919:Placebos; D017475:Receptors, Nerve Growth Factor; D002443:Ceftriaxone; D003907:Dexamethasone
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