Basic fibroblast growth factor protects auditory neurons and hair cells from glutamate neurotoxicity and noise exposure.
OBJECTIVE
To determine the protective effects of basic fibroblast growth factor (bFGF) on cochlear neurons and hair cells in vitro and in vivo.


METHODS
In Experiment I, cultured spiral ganglion neurons (SGNs) prepared from postnatal Day 3 mice were exposed to 20 mM glutamate for 2 h before the culture medium was replaced with fresh medium containing 0, 25, 50 or 100 ng/ml bFGF. Fourteen days later, all cultures were fixed with 4% paraformaldehyde and stained with 1% toluidine blue. The number of surviving SGNs was counted and the length of the neurites of the SGNs was measured. In Experiment II, in vivo studies were carried out with guinea pigs in which bFGF or normal saline was injected intramuscularly to assess possible protective effects of bFGF on cochlear hair cells and to accelerate the recovery of the auditory brainstem response (ABR). The ABRs were measured before, immediately after and 2 and 4 weeks after exposure to noise.


RESULTS
Exposure to 20 mM glutamate for 2 h resulted in an inhibition of neurite outgrowth of SGNs and an increase in cell death. Treatment of the cultures with bFGF led to promotion of neurite outgrowth and an increase in the number of surviving SGNs. In Experiment II, significant (p < 0.05) differences in ABR thresholds were observed between the groups injected with bFGF and saline (t = 2.689) at 4 weeks after noise exposure. Cochleae were removed and hair cell loss analyzed in surface preparations prepared from all experimental animals. Acoustic trauma caused loss of 240 and 2160 inner hair cells in the groups injected with bFGF and saline, respectively. Similarly, more outer hair cells were lost in the normal saline injection group (99,291) than in the group treated with bFGF (70,377).


CONCLUSIONS
Our results demonstrate that bFGF protects SGNs against glutamate neurotoxicity in vitro. In addition, treatment with bFGF protects hair cells from acoustic trauma.
Zhai
Suo-Qiang
SQ
Institute of Otorhinolaryngology, General Hospital of PLA, Beijing, People's Republic of China. zhaisq@plagh.com.cn
Wang
Da-Jun
DJ
Wang
Jia-Ling
JL
Han
Dong-Yi
DY
Yang
Wei-Yan
WY
D000818:Animals; D001300:Audiometry, Evoked Response / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003056:Cochlear Nerve / Q000166:cytology / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D018698:Glutamic Acid / Q000633:toxicity; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects*; D006317:Hearing Loss, Noise-Induced / Q000517:prevention & control*; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*; D009622:Noise / Q000009:adverse effects; D013136:Spiral Ganglion / Q000166:cytology
D016222:Fibroblast Growth Factor 2; D018698:Glutamic Acid