Bhagyalakshmi G. Shivapuja

Lipid peroxidation inhibitor attenuates noise-induced temporary threshold shifts

The purpose of this study was to investigate the protective effects of U74389F (Upjohn Co. Kalamazoo, MI), a 21-aminosteroid/lipid peroxidation inhibitor, and a member of the lazaroid drug class, on temporary threshold shifts in animals exposed to prolonged noise stimulation. Animals treated with U74389F and exposed to noise showed attenuated cochlear action potential threshold (CAP) shifts and cochlear microphonic (CM) when compared to non-drug treated noise-exposed subjects. These data suggest that inhibition of FOR induced lipid peroxidation is an important mechanism in noise-induced asymptotic temporary threshold shifts.

Relationships among psychoacoustic judgments, speech understanding ability and self-perceived handicap in tinnitus subjects.

Tinnitus is often a disturbing symptom which affects 6-20% of the population. Relationships among tinnitus pitch and loudness judgments, audiometric speech understanding measures and self-perceived handicap were evaluated in a sample of subjects with tinnitus and hearing loss (THL). Data obtained from the THL sample on the audiometric speech measures were compared to the performance of an age-matched hearing loss only (HL) group. Both groups had normal hearing through 1 kHz with a sloping configuration of < or = 20 dB/octave between 2-12 kHz. The THL subjects performed more poorly on the low predictability items of the Speech Perception in Noise Test, suggesting that tinnitus may interfere with the perception of speech signals having reduced linguistic redundancy. The THL subjects rated their tinnitus as annoying at relatively low sensation levels using the pitch-match frequency as the reference tone. Further, significant relationships were found between loudness judgment measures and self-rated annoyance. No predictable relationships were observed between the audiometric speech measures and perceived handicap using the Tinnitus Handicap Questionnaire. These findings support the use of self-report measures in tinnitus patients in that audiometric speech tests alone may be insufficient in describing an individuals reaction to his/her communication breakdowns.

Pentoxifylline Maintains Cochlear Microcirculation and Attenuates Temporary Threshold Shifts Following Acoustic Overstimulation

The etiology of noise-induced hearing loss is poorly understood despite years of clinical experience and experimental investigations. One potential mechanism which may contribute to noise-induced temporary threshold shifts (TTS) are vascular pathologies in the microcirculation of the cochlea. Several studies have demonstrated histologic evidence of reduced cochlear blood flow following noise exposure. Recent studies utilizing intravital microscopy (IVM) complement these histologic studies and furthermore demonstrate localized ischemia during noise exposure. The purpose of the current study was to attempt to maintain cochlear blood flow during noise exposure by treating with pentoxifylline, a xanthine derivative which promotes blood flow in capillary beds. The possibility that preserved cochlear microcirculation with pentoxifylline treatment attenuates noise-induced TTS was also examined in this study. The results show treatment with pentoxifylline maintains cochlear microcirculation as assessed by continuous red blood cell movement through capillaries. Pentoxifylline treatment did not prevent vasoconstriction or increased permeability often observed in the cochlear microvasculature during noise. Treatment with this drug reduced noise-induced TTS.

Effects of kynurenic acid as a glutamate receptor antagonist in the guinea pig

Abstract 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-synaptic receptors and the initiation of a destructive cascade of cellular events, thus leading to neuronal degeneration and NIHL. The purpose of this study was to determine whether this apparent excitotoxicity can be attenuated 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 action potentials (CAP) thresholds and cochlear microphonics (CM) were recorded. Group I was treated with physiologic saline as a vehicle control applied to the round window membrane that was followed by 110 dB SPL wide-band noise 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 noise levels of CAP thresholds and CM were then obtained. Noise exposure in the control group caused a significant temporary threshold shift (TTS) of 30–40 dB across the frequencies tested (from 3 kHz to18 kHz). Animals that received 5 mM KYNA prior to noise exposure (group II) showed statistically significant protection against noise-induced damage and demonstrated a minimal TTS ranging between 5 and 10 dB at the same frequencies. Animals in group 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 results show that antagonizing glutamate receptors can attenuate noise-induced TTS, suggesting that glutamate excitotoxicity may play a role in acoustic trauma.

Auditory intensity discrimination in the chinchilla

A positive reinforcement conditioning procedure was used to train chinchillas to respond to intensity differences between successively occurring tone bursts. Intensity difference limens were measured at 0.5, 1, 4, and 8 kHz at five intensities ranging from 10- to 55-dB sensation level. The intensity difference limen decreased from approximately 8 dB near threshold to approximately 3.5 dB at the highest level. The intensity difference limens for the chinchilla were considerably larger than those for humans as well as several other mammals; however, the results were similar to those obtained for the parakeet. The present results from intensity discrimination appeared to be related to previous data for the discrimination of amplitude modulated noise.

Acute effects of cocaine on cochlear function

The effects of a single administration of cocaine on the cochlea was evaluated by measuring amplitude-intensity functions of the N1 response of the auditory nerve. Amplitude-intensity functions of the N1 response to tone-pips of 500 Hz, 1, 2, 4 and 8 kHz were obtained before and after intraperitoneal injection of either saline, 3 mg/kg or 25 mg/kg of cocaine. N1 amplitudes were decreased after the administration of cocaine and this reduction was found to be dose dependent. The influence of cocaine on cochlear blood flow (CBF) was examined in order to test the possibility that cocaine induced reductions in CBF underlie these electro-physiological changes. Corresponding decreases in cochlear blood flow after cocaine exposure were observed.

Effects of repeated cocaine injections on cochlear function

The effects of repeated cocaine administration on cochlear function were evaluated by measuring amplitude-intensity and latency-intensity functions of the whole-nerve action potential of the auditory nerve. Whole-nerve action potential input/output functions obtained using tone-pips of 0.5, 1, 2, 4 and 8 kHz in a group of cocaine-treated subjects were compared with those obtained in saline-treated animals. All measurements were made 24 h after the last treatment. Amplitudes of whole-nerve action potentials were enhanced in the cocaine-treated animals compared to the control group. No statistically significant differences in latency-intensity functions were seen after cocaine treatment. The effect of chronic cocaine exposure also was examined on catecholamine innervation in the cochlea using immunohistochemical techniques. The density of adrenergic innervation was reduced in the cocaine-treated animals.

α1-Adrenergic Receptors in the Mammalian Cochlea

Liu SY, Pitovski DZ, Shivapuja BG. α-adrenergic receptors in the mammalian cochlea. Acta Otolaryngol (Stockh) 1996; 116: 710-713.The presence of α1, -adrenergic receptors in the mammalian cochlea has previously been suggested by physiological experiments using antagonists specific to the receptor. However, the characterises of adrenergic receptors in the cochlea have not been described. by employing [H]-prazosin, high affinity, specific binding sites with characteristics of α1, -adrenergic receptors have now been identified and characterized in the chinchilla cochlea. Analysis of the specific [H]-prazosin binding indicates that prazosin binds to a single class of high-affinity sites with a dissociation constant, kd, of 2.9 10−9 M and a maximum number of binding sites, Bmax, of 30 fmol/mg dry tissue. Furthermore, the binding characteristics suggest that these receptors may be related to the microvasculature of the cochlea. These results provide a rational basis for the observed actions of a-adrenergic drug...

α1-Adrenergic receptor antagonist blocks acute cocaine action on the compound action potential of the auditory nerve in the chinchilla

Acute systemic cocaine injection is known to significantly decrease the compound action potential (CAP) amplitude of the auditory nerve. In an attempt to elucidate the mechanism underlying this phenomenon, the present study investigated the influence of prazosin, an adrenergic alpha 1-receptor antagonist, on the effect of cocaine on the CAP. Amplitude-intensity functions at 1 and 8 kHz were obtained before and after treatment with cocaine (experimental group) or saline (control group) in prazosin pretreated subjects. The characteristic reduction in CAP amplitude after an acute cocaine injection was blocked by 0.05 mg/kg prazosin. When subjects were re-injected with cocaine or saline one h after prazosin, the reduction in CAP amplitude following cocaine injection had recovered.

Response of auditory‐nerve fibers to intensity increments in a multitone complex: Neural correlates of profile analysis

Recent psychophysical studies have shown that the detection of an intensity increment superimposed on the center component (1 kHz) of a multitone complex (1, 3, 7, or 11 components) improves as more components are added outside of the critical band. It has been suggested that this form of intensity discrimination is based on a change in the neural profile. To test this hypothesis, neural profiles were constructed by plotting the degree of phase locking to the 1-kHz tone as a function of each units characteristic frequency (CF). Neural phase-locking profile to the 1-component signal at 1 kHz had a broad peak; however, the neural profile became narrower as the number of components in the signal increased. The just detectable increment for the 1-component condition was -5 dB re: 1000-Hz component level (3.86-dB increment plus component level re: component level), whereas, for the 3-, 7-, and 11-component conditions, it was -15 dB re: component level (1.42 dB). The neural and psychophysical IDL for the chinchilla were similar for the 1-component condition. However, the overall trends in the psychophysical and neural data are different. In the psychophysical studies IDL is typically poorest in the 3-component condition and improves when more components are added. By contrast, the neural IDL was poorest in the 1-component condition and improved when more components were added. In the multicomponent conditions, units with CFs in 492-1380 Hz were found to be more sensitive in detecting the intensity increment to the 1000-Hz component.