Glial cell line-derived neurotrophic factor has a dose dependent influence on noise-induced hearing loss in the guinea pig cochlea.
We examined the effectiveness of glial cell line-derived neurotrophic factor (GDNF) to attenuate cochlear damage from intense noise stress. Subjects were exposed to 115 dB SPL one octave band noise centered at 4 kHz for 5 h. They received artificial perilymph with or without GDNF into the left scala tympani at 0.5 microliter/h from 4 days before noise exposure through 8 days following noise exposure. Different concentrations of GDNF (1 ng/ml, 10 ng/ml, 100 ng/ml, and 1 microgram/ml) were applied chronically directly into the guinea pig cochlea via a microcannula and osmotic pump. Noise-induced hearing loss was assessed with pure tone auditory brainstem responses (at 2, 4, 8 and 20 kHz), measured prior to surgery, 1 day before noise exposure, and 7 days following noise exposure. Subjects were killed on day 8 following exposure for histological preparation and quantitative assessment of hair cell (HC) damage. A dose-dependent protective effect of GDNF on both sensory cell preservation and hearing function was found in the treated ears. At 1 ng/ml, GDNF showed no significant protection; at 10 ng/ml, GDNF showed significant HC protection; and at 100ng/ml, it was greater and bilateral. At 1 microgram/ml, GDNF appeared to have a toxic effect under noise stress in some cochleae. These findings indicate that GDNF at certain concentrations can effectively protect the inner ear from noise-induced hearing loss.
Shoji
F
F
Kresge Hearing Research Institute, The University of Michigan, 1301 East Ann Street, Ann Arbor, MI, USA.
Yamasoba
T
T
Magal
E
E
Dolan
D F
DF
Altschuler
R A
RA
Miller
J M
JM
D000818:Animals; D002460:Cell Line; D003051:Cochlea / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology; D006309:Hearing / Q000187:drug effects; D006317:Hearing Loss, Noise-Induced / Q000473:pathology / Q000517:prevention & control*; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D009622:Noise / Q000009:adverse effects; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins