Age-related Hearing Loss and its Association with Reactive Oxygen Species and Mitochondrial DNA damage

Age-related hearing loss, known as presbyacusis, is characterized by the progressive deterioration of auditory sensitivity associated with the aging process and is the leading cause of adult auditory deficiency in the USA. Presbyacusis is described as a progressive, bilateral, high-frequency hearing loss that is manifested on audiometric assessment by a moderately sloping pure tone audiogram. Approximately 23% of the population between 65 and 75 years of age, and 40% of the population older than 75 years of age are affected by this condition. It was estimated in 1980 that 11% of the population was 76 years or older and this number is expected to almost double by the year 2030. When one considers that the population over 65 years of age is experiencing the most accelerated development of hearing loss, the potential socioeconomic ramifications are staggering. Curiously, the frequency of presbyacusis varies across different societies. This discrepancy has been attributed to many factors including genetics, diet, socioeconomic factors, and environmental variables. The purpose of this article is to review the various molecular mechanisms underlying presbyacusis and to offer insights into potential methods of mitigating the effects of aging on hearing impairment

The vascular mechanism of action of betahistine in the inner ear of the guinea pig

The aim of this study was to investigate the mechanism and site of action of betahistine dihydrochloride in the inner ear of the guinea pig. Betahistine-evoked increases in cochlear blood flow (CBF) have been presumed to be due to the drug effect on the later wall capillary bed or larger feeding vessels in the cochlea vascular system. As such, the mechanism of action could be due to inhibition of H 3 receptors. Betahistine may also have a direct effect on postsynaptic H 1 /H 2 receptors and/or an effect modulated by other autonomic receptors. Betahistine-evoked CBF responses were assessed by laser Doppler flowmetry in the presence of an H 3 agonist ( α N -methylhistamine dihydrochloride), an H 3 antagonist (thioperamide), an H 2 antagonist (cimetidine) or an α 2 antagonist (idazoxan). The effects of betahistine on circulation in the anterior inferior cerebellar artery (AICA) and ipsilateral stria vascularis (SV) were assessed using intravital microscopy (IVM). Findings showed that betahistine increased CBF and reduced systemic blood pressure (BP). In contrast, α N -methylhistamine dihydrochloride had no effect on baseline CBF or BP and did not influence betahistine-induced increases in CBF. Thioperamide reversed the effects of betahistine on CBF, but had no effect on baseline CBF or BP. Cimetidine had no marked effect on baseline CBF or betahistine-induced increases in CBF Idazoxan had no consistent effects on baseline CBF, but abolished the effect of betahistine on CBF. The mean increase of red blood cell velocity in SV capillaries was 15% and occurred without a demonstrable change in capillary diameters. In contrast, the diameter of the AICA increased by 17–20%, indicating that betahistine-evoked increases in CBF resulted primarily from vasodilatation of the AICA. We suggest that this effect may be mediated via presynaptic H 3 heteroreceptors and autonomic α 2 receptors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42216/1/405-255-3-119_82550119.pd

Noise-induced changes in red blood cell velocity in lateral wall vessels of the rat cochlea

The effects of loud sound on the microvasculature of the cochlea are not well characterized or understood. Morphological changes in the stria vascularis and changes in blood flow are known to occur during or following sound stimulation, however the effects on cochlear blood flow appear to be complex. Studies have shown that noise exposure may produce increases in blood flow, decreases in blood flow, or no measureable change in blood flow. These inconsistent results probably reflect the various noise exposure parameters, the animal model used, and could be a function of the specific procedures utilized to assess blood flow changes.The purpose of the current study was to investigate the effects of one specific class of sound exposure (high intensity noise) on red blood cell velocity in the capillaries of the second turn of the rat cochlea using intravital microscopy. This class of sound exposure was selected in order to attempt a confirmation of previous findings of increased blood flow (Perlman and Kimura, 1962) using the quantitative technique of red blood cell velocity measurement. Following determination of pre-exposure red blood cell velocities in capillaries of the rat cochlea second turn, animals were exposed to 133 dB or 110 dB broad-band noise for ten minutes. The red blood cell velocity was recorded continuously during the exposure. Exposure to both sound intensities disrupted stable and orderly baseline flow patterns and resulted in overall intensity-dependent increases in red blood cell velocity. Qualitatively, we observed aggregations of red blood cells, local vasoconstriction and directional reversals of red blood cell flow during noise exposure at both intensities. These results may represent the interaction of several mechanisms that participate in the control of blood flow in the cochlea during noise exposure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29430/1/0000511.pd

Pentoxifylline increases cochlear blood flow while decreasing blood pressure in guinea pigs

The effects of pentoxifylline on cochlear blood flow (CoBF) were investigated in anesthetized guinea pigs by laser Doppler flowmetry and intravital microscopy red blood cell velocity measurement. Intra-arterial infusion of pentoxifylline (3, 4, and 5 mg/kg/min) produced dose-dependent reductions in blood pressure, accompanied by significant elevations in CoBF that were not dose-dependent. These results are in general agreement with previous findings from our laboratory utilizing normotensive and spontaneously hypertensive rats, however, in contrast with rats, guinea pigs revealed an initial decrease in CoBF followed by an increase. Also, pentoxifylline produced relatively smaller elevations in CoBF in guinea pigs as compared with those previously reported in rats. Taken together these results support the hypothesis that pentoxifylline increases vascular perfusion by decreasing blood viscosity and increasing the plasticity of red blood cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28442/1/0000229.pd

The influence of intra-arterial infusion of arginine vasopressin on cochlear blood flow in the rat

Intra-arterially infused arginine vasopressin (AVP) elevated systemic blood pressure (BP) in the Sprague-Dawley rat according to a dose-response pattern while cochlear blood flow (CoBF), as measured by laser Doppler flowmetry, was elevated only at the highest dose. Skin blood flow (SBF) decreased significantly with AVP infusion. The local infusion of AVP into the anterior inferior cerebellar artery (AICA), which supplies the common cochlear artery, produced significant dose-dependent reductions in CoBF with no changes in systemic blood pressure. Pretreatment of the local cochlear supplying vessels with an AVP-specific VI receptor antagonist attenuated subsequent AVP-induced decreases in CoBF, thereby demonstrating specificity of the response. These results suggest that CoBF is reasonably stable in response to systemic AVP infusion until blood pressure exceeds an elevation from base level of approximately + 60 mm Hg. One of the mechanisms responsible for this autoregulatory response may be vasoconstriction mediated by the interaction of vasoactive peptides such as AVP and its receptors located in the vasculature of the inner ear or in the more peripheral vessels directly supplying the cochlea.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29134/1/0000173.pd

Practice Management Guidelines for the Diagnosis and Management of Injury in the Pregnant Patient: The EAST Practice Management Guidelines Work Group

Trauma during pregnancy has presented very unique challenges over the centuries. From the first report of Ambrose Pare of a gunshot wound to the uterus in the 1600s to the present, there have existed controversies and inconsistencies in diagnosis, management, prognostics, and outcome. Anxiety is heightened by the addition of another, smaller patient. Trauma affects 7% of all pregnancies and requires admission in 4 of 1000 pregnancies. The incidence increases with advancing gestational age. Just over half of trauma during pregnancy occurs in the third trimester. Motor vehicle crashes comprise 50% of these traumas, and falls and assaults account for 22% each. These data were considered to be underestimates because many injured pregnant patients are not seen at trauma centers. Trauma during pregnancy is the leading cause of nonobstetric death and has an overall 6% to 7% maternal mortality. Fetal mortality has been quoted as high as 61% in major trauma and 80% if maternal shock is present. The anatomy and physiology of pregnancy make diagnosis and treatment difficult

Effects of Resveratrol on Acoustic Trauma

OBJECTIVE: The purpose of the study is to test the ability of resveratrol to protect the auditory system from reactive oxygen species (ROS)-mediated noise damage. Oxidative stress is mediated by ROS, which are known to cause cellular and molecular damage. Interfering with this process, using ROS inhibitors/scavengers such as antioxidants has shown promise in protecting specific systems from oxidative damage. Among the antioxidants receiving recent attention is resveratrol, an active component in red wine. STUDY DESIGN AND SETTING: Ten Fischer rats were used for this study. The experimental group (n = 5) received 7 weeks of resveratrol treatment (430/μg/kg/day), by gavage, and the control group (n = 5) received normal saline solution by gavage. Baseline auditory brainstem responses (3, 6, 9, 12 and 18 kHz) were determined for both groups. After 21 days, animals were exposed to noise (105 dB, 4500 to 9000 Hz for 24 hours). Postnoise auditory brainstem responses were assessed at 4 recovery time points: immediate, at 3 days, 7 days, and 4 weeks after noise exposure. RESULTS: Results demonstrate that the resveratrol group showed reduced threshold shifts compared with the control group after noise exposure. These shifts were significantly different between groups at 6 and 9 kHz (P \u3c 0.05), corresponding to the region most represented by the frequency of the traumatic noise. CONCLUSION/SIGNIFICANCE: Initial studies in our laboratory as well as other investigators have shown the importance of specific antioxidant therapy in the prevention of ischemic, noise, and age related hearing loss. The current study demonstrates a protective effect of resveratrol on noise-induced hearing loss

Angiotensin II-induced changes in cochlear blood flow and blood pressure in normotensive and spontaneously hypertensive rats

Previous investigations in our laboratory have measured significant increases in the circulating levels of the potent vasoconstric-tive hormone, angiotensin II (AII; 26 and 64 pg/100 [mu]l plasma, normal and noise exposed, respectively), during and following noise exposure in the alert rat (Wright et al., 1981). In the present study, these levels were approximated through intra-arterial infusion in the anesthetized spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat. Laser Doppler flowmeter measurements of cochlear blood flow (CBF) indicated that despite equivalent All-induced elevations in systemic blood pressure, CBF in the SHR did not increase to the levels measured in the WKY. Pretreatment with the specific angiotensin receptor antagonist sarile, (Sar1,Ile8-AII), reduced All-induced elevations in systemic blood pressure in members of both strains, but did not change the overall pattern of CBF. These results indicate that SHRs may have a compromised cochlear circulation that is refractory to increases in systemic blood pressure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27304/1/0000325.pd

Cochlear blood flow autoregulation in Wistar-Kyoto rats

Wistar-Kyoto rats (WKY) were intra-arterially infused with angiotensin II (AII) or phenylephrine for 10 min. Both vasoactive compounds produced an initial increase in cochlear blood flow (CoBF) as measured by laser Doppler flowmetry, followed by a slow steady return to baseline, despite sustained elevations in systemic blood pressure. These results suggest autoregulation of CoBF in the WKY rat. In a second experiment, All was infused directly into the anterior inferior cerebellar artery (AICA) which feeds the cochlear artery. Significant reductions in CoBF were noted without changes in systemic blood pressure. Pretreatment with the specific angiotensin-receptor antagonist, sarthran (Sar1, Thr8-AII), diminished subsequent AII-induced reductions in CoBF. These results indicate that All binding to vascular receptors may induce vasoconstriction in the supplying vessels of the cochlea, and thus, the interaction of blood-home All and vascular angiotensin receptors may participate in the autoregulation of CoBF.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27804/1/0000209.pd