Effects of kynurenic acid as a glutamate receptor antagonist in the guineapig

Glutamate excitotoxicity is implicated in both the genesis of neural injury and noise-induced hearing loss (NIHL). Acoustic overstimulation may result in excessive synaptic glutamate, resulting in excessive binding to post-sy naptic receptors and the initiation of a destructive cascade of cellular ev ents, thus leading to neuronal degeneration and NIHL. The purpose of this s tudy was to determine whether this apparent excitotoxicity can be attenuate d by kynurenic acid (KYNA), a broad-spectrum glutamate receptor antagonist, and protect against noise-induced temporary threshold shifts (TTS). Guinea pigs were randomly assigned to three separate groups. Baseline compound ac tion potentials (CAP) thresholds and cochlear microphonics (CM) were record ed. Group I was treated with physiologic saline as a vehicle control applie d to the round window membrane that was followed by 110 dB SPL wide-band no ise for 90 min. Group II received 5 mM KYNA followed by noise exposure, and group III received 5 mM KYNA alone without noise exposure. Post-drug and n oise levels of CAP thresholds and CM were then obtained. Noise exposure in the control group caused a significant temporary threshold shift (TTS) of 3 0-40 dB across the frequencies tested (from 3 kHz to 18 kHz). Animals that received 5 mM KYNA prior to noise exposure (group II) showed statistically significant protection against noise-induced damage and demonstrated a mini mal TTS ranging between 5 and 10 dB at the same frequencies. Animals in gro up III receiving KYNA without noise exposure showed no change in thresholds . Additionally, cochlear microphonics showed no considerable difference in threshold shifts when controls were compared to KYNA-treated animals. These re suits show that antagonizing glutamate receptors can attenuate noise-in duced TTS, suggesting that glutamate excitotoxicity may play a role in acou stic trauma.