Protective effect of magnesium and MK 801 on hypoxia-induced hair cell loss in new-born rat cochlea.
Hypoxia is a pathogenetic factor in various inner ear diseases, and increasing importance is attached to the protection of the cochlea from traumatic influences. It was recently demonstrated in guinea pigs that magnesium can significantly reduce ischemia- and impulse noise-induced hearing loss. The aim of this study was to evaluate if magnesium has a protective effect on hypoxia-induced hair cell loss using an in vitro model of the new-born rat cochlea In view of the NMDA receptor-antagonistic action of magnesium, we tested MK 801, a highly potent and selective non-competitive NMDA receptor antagonist. Organotypic cochlea cultures were exposed to hypoxia (pO2 = 10-20 mm Hg at 37 degrees C) in DMEM medium containing magnesium (0.75 or 3.0 mmol/l) or MK801 (1 or 10 micromol/l) for 24 or 36 h. The cultures were phalloidin-labeled for counting the number of outer and inner hair cells (OHC/IHC). The mean damage in normoxic controls was 1-4%. IHC revealed a significantly higher susceptibility to hypoxia than OHC. In the normal magnesium group (0.75 mmol/l), 36-hour exposure to hypoxia caused a mean loss of about 25% OHC and 60% IHC. In the groups treated with either 3.0 mmol magnesium or 10 microm MK 801, the damage was significantly reduced to about 10% in OHC and 35% in IHC. This study supports previous in vivo observations in the guinea pig demonstrating the protective effects of magnesium on noise-induced impairment of inner ear oxygenation.
König
Ovidiu
O
Department of Otorhinolaryngology, Charité Hospital, Humboldt University, Schumannstrasse 20-21, 10117 Berlin, Germany.
Winter
Elisabeth
E
Fuchs
Julia
J
Haupt
Heidemarie
H
Mazurek
Birgit
B
Weber
Nina
N
Gross
Johann
J
D000818:Animals; D000831:Animals, Newborn; D003051:Cochlea / Q000473:pathology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism / Q000473:pathology*; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism / Q000473:pathology*; D000860:Hypoxia; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D010590:Phalloidine / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013997:Time Factors
D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D010590:Phalloidine; D016291:Dizocilpine Maleate; D008274:Magnesium; D010100:Oxygen