Women Physicians and Promotion in Academic Medicine.

BACKGROUND: In 2000, a landmark study showed that women who graduated from U.S. medical schools from 1979 through 1997 were less likely than their male counterparts to be promoted to upper faculty ranks in academic medical centers. It is unclear whether these differences persist. METHODS: We merged data from the Association of American Medical Colleges on all medical school graduates from 1979 through 2013 with faculty data through 2018, and we compared the percentages of women who would be expected to be promoted on the basis of the proportion of women in the graduating class with the actual percentages of women who were promoted. We calculated Kaplan-Meier curves and used adjusted Cox proportional-hazards models to examine the differences between the early cohorts (1979-1997) and the late cohorts (1998-2013). RESULTS: The sample included 559,098 graduates from 134 U.S. medical schools. In most of the cohorts, fewer women than expected were promoted to the rank of associate or full professor or appointed to the post of department chair. Findings were similar across basic science and clinical departments. In analyses that included all the cohorts, after adjustment for graduation year, race or ethnic group, and department type, women assistant professors were less likely than their male counterparts to be promoted to associate professor (hazard ratio, 0.76; 95% confidence interval [CI], 0.74 to 0.78). Similar sex disparities existed in promotions to full professor (hazard ratio, 0.77; 95% CI, 0.74 to 0.81) and appointments to department chair (hazard ratio, 0.46; 95% CI, 0.39 to 0.54). These sex differences in promotions and appointments did not diminish over time and were not smaller in the later cohorts than in the earlier cohorts. The sex differences were even larger in the later cohorts with respect to promotion to full professor. CONCLUSIONS: Over a 35-year period, women physicians in academic medical centers were less likely than men to be promoted to the rank of associate or full professor or to be appointed to department chair, and there was no apparent narrowing in the gap over time. (Funded by the University of Kansas Medical Center Joy McCann Professorship for Women in Medicine and the American Association of University Women.).

Methionine Sulfoxide Reductase A Knockout Mice Show Progressive Hearing Loss and Sensitivity to Acoustic Trauma.

Methionine sulfoxide reductases (MsrA and MsrB) protect the biological activity of proteins from oxidative modifications to methionine residues and are important for protecting against the pathological effects of neurodegenerative diseases. In the current study, we characterized the auditory phenotype of the MsrA knockout mouse. Young MsrA knockout mice showed small high-frequency threshold elevations for auditory brainstem response and distortion product otoacoustic emission compared to those of wild-type mice, which progressively worsened in older MsrA knockout mice. MsrA knockout mice showed an increased sensitivity to noise at young and older ages, suggesting that MsrA is part of a mechanism that protects the cochlea from acoustic damage. MsrA mRNA in the cochlea was increased following acoustic stimulation. Finally, expression of mRNA MsrB1 was compromised at 6 months old, but not in younger MsrA knockout mice (compared to controls). The identification of MsrA in the cochlea as a protective mediator from both early onset hearing loss and acoustic trauma expands our understanding of the pathways that may induce protection from acoustic trauma and foster further studies on how to prevent the damaging effect of noise exposure through Msr-based therapy.

Hearing, reactive metabolite formation, and oxidative stress in cochleae after a single acute overdose of acetaminophen: an in vivo study.

CONTEXT: Although the liver is the primary target organ in acetaminophen (APAP) toxicity, other organs are affected. Previous data suggested that chronic APAP abuse can be ototoxic and the mechanism involves APAP-induced oxidative stress and reactive metabolite (N-acetyl-p-benzoquinone imine, NAPQI)-induced endoplasmic reticulum stress. However, the effect of a single acute overdose on hearing has not been tested. OBJECTIVES: To determine if a single acute APAP overdose causes hearing damage, and to explore possible mechanisms of APAP ototoxicity. MATERIALS AND METHODS: Male C57BL/6 J mice were treated with a single human-relevant overdose of APAP (300 mg APAP per kg bodyweight). Blood, liver and cochleae were harvested at 0, 2, 6 and 24 h post-APAP. In some mice, auditory brainstem responses (ABRs) to a range of frequencies were measured at 24 h. The furosemide plus kanamycin (FS/K) model of drug ototoxicity was used as a positive control for hearing loss. NAPQI formation after APAP was assessed by measuring glutathione depletion and covalent protein binding, and oxidative stress was assessed by measuring glutathione disulfide. RESULTS: There was no evidence of reactive metabolite formation or hearing loss after a single overdose of APAP at a clinically relevant dose. However, there was a transient increase in oxidative stress. DISCUSSION: Although a single acute overdose was not ototoxic, there was evidence of oxidative stress which may support a role for oxidative stress in hearing loss due to chronic APAP abuse. CONCLUSION: A single human-relevant acute overdose of APAP causes transient oxidative stress in cochleae but not hearing loss.

Histochemical and fluorescent analyses of mitochondrial integrity in chick auditory neurons following deafferentation.

BACKGROUND: Neurons rely exclusively on mitochondrial oxidative phosphorylation to meet cellular energy demands, and disruption of mitochondrial function often precipitates neuronal cell death. Auditory neurons in the chick brain stem (n. magnocellularis [NM]) receive glutamatergic innervation exclusively from ipsilateral eighth nerve afferents. Cochlea removal permanently disrupts afferent support and ultimately triggers apoptotic cell death in 30-50% of ipsilateral, deafferented neurons. Here, we evaluated whether disruption of mitochondrial function occurs during deafferentation-induced neuronal cell death. PURPOSE: To determine whether mitochondrial dysfunction occurs preferentially within dying NM neurons. RESEARCH DESIGN: An experimental study. All birds underwent unilateral cochlea removal. Normally innervated neurons contralateral to surgery served as within-animal controls. STUDY SAMPLE: Hatchling broiler chickens between 8 and 12 days of age served as subjects. A total of 62 birds were included in the study. INTERVENTION: Cochlea removal was performed to deafferent ipsilateral NM neurons and trigger neuronal cell death. DATA COLLECTION AND ANALYSIS: Following unilateral cochlea removal, birds were sacrificed 12, 24, 48, or 168 hours later, and brain tissue was harvested. Brainstems were sectioned through NM and evaluated histochemically for oxidative enzyme reaction product accumulation or reacted for Mitotracker Red, an indicator of mitochondrial membrane potential (m) and cytoplasmic TdT-mediated dUTP Nick-End Labeling (TUNEL), an indicator of cell death. Histochemical staining intensities for three mitochondrial enzymes, succinate dehydrogenase (SDH), cytochrome c oxidase (CO), and ATP synthase (ATPase) were measured in individual neurons and compared in ipsilateral and contralateral NM. Comparisons were made using unpaired t-tests (CO) or Kruskal Wallis one way ANOVA followed by Dunn's post hoc pairwise comparisons (ATPase, SDH). Mitotracker Red tissue was examined qualitatively for the presence of and extent of colocalization between Mitotracker Red and TUNEL label in NM. RESULTS: RESULTS showed global upregulation of all three oxidative enzymes within deafferented NM neurons compared to contralateral, unperturbed NM neurons. In addition, differential SDH and ATPase staining intensities were detected across neurons within the ipsilateral nucleus, suggesting functional differences in mitochondrial metabolism across deafferented NM. Quantitative analyses revealed that deafferented neurons with preferentially elevated SDH and ATPase activities represent the subpopulation destined to die following cochlea removal. In addition, Mitotracker Red accumulated intensely within the subset of deafferented NM neurons that also exhibited cytoplasmic TdT-mediated dUTP Nick-End Labeling (TUNEL) and subsequently died. CONCLUSIONS: Taken together, our results demonstrate that a subset of deafferented NM neurons, presumably those that die, preferentially upregulates SDH, perhaps via the tricarboxylic acid (TCA) cycle. These same neurons undergo ATPase uncoupling and an eventual loss of Deltapsi(m).

Early Onset Region and Cell Specific Alterations of Doublecortin Expression in the CNS of Animals with Sound Damage Induced Hearing Loss.

Sound damage induced hearing loss has been shown to elicit changes in auditory and non-auditory brain regions. A protein critical for neuronal migration and brain development, doublecortin (DCX), has been used as a marker of central nervous system (CNS) neuroplasticity. DCX is expressed in unipolar brush cells (UBCs) of the dorsal cochlear nucleus (DCN), cerebellar parafloccular lobe (PFL) and neuronal precursor cells in the sub-granular zone of the hippocampal dentate gyrus (DG). Sound damage induced hearing loss has been shown to differentially impact DCX expression months later. To identify earlier alterations in DCX expression, we utilized immunohistochemistry to detect DCX protein in three brain regions (DCN, PFL, DG) approximately one month following unilateral sound damage. Auditory brainstem response was used to measure hearing loss. Unilateral hearing loss was evident in all sound damaged animals. Hearing loss related decreases in DCX expression were evident bilaterally in the DG while hearing loss related increases in DCX expression were evident bilaterally in the PFL. No changes to DCX expression were evident in the auditory DCN. Gap detection was used to assess whether this sound damage paradigm induced tinnitus-like behavior. However, results obtained from this behavioral test as used here were inconclusive and are presented here only as a guide to others wishing to design similar studies.

Association of Skin and Cartilage Variables With Composite Graft Healing in a Rabbit Model.

IMPORTANCE: Composite grafting in nasal reconstruction involves transplanting auricular chondrocutaneous grafts, but the optimal design of these grafts is unknown. OBJECTIVES: To investigate the ideal ratio of skin to cartilage as well as study the importance of the perichondrial attachment for graft survival. DESIGN, SETTING, AND PARTICIPANTS: A New England white rabbit model was used in this study, performed at the Laboratory for Animal Research at University of Kansas Medical Center from January 25 to March 18, 2016. Four varying designs of chondrocutaneous auricular grafts were transplanted to dorsal back defects, with a total of 10 grafts per treatment arm completed. The following 4 chondrocutaneous circular grafts were designed: group A, 1.5-cm diameter graft of equal skin to cartilage ratio; group B, 2.0-cm diameter skin and 1.5-cm diameter cartilage; group C, 1.5-cm diameter skin and 2.0-cm diameter cartilage; and group D, 1.5-cm diameter skin and cartilage separated and placed back together in a layered fashion. Grafts were observed until postoperative day 21, harvested, and evaluated with visual observation as well as histopathologic assessment. MAIN OUTCOMES AND MEASURES: Visually graded areas of survival were marked by 2 blinded academic facial plastic surgeons and calculated for approximate survival. Hematoxylin-eosin-stained, paraffin-embedded 5-µm slides were evaluated for overall survival rate, rate of cartilage necrosis, and mean vessel density per high-power field. In both cases, observers were blinded as to the study group. RESULTS: Visual assessments of the 5 female rabbits showed significant agreement between surgeons and consistency, with a Spearman coefficient of 0.84 and an intraclass correlation of 0.98. Group D (skin and cartilage separation) was visually graded to have significantly decreased mean survival (45.4%; 95% CI, 23.3%-67.4%) compared with group A (mean survival, 97.4%; 95% CI, 94.8%-99.9%; P < .001), group B (mean survival, 87.6%; 95% CI, 69.9%-100%; P = .004), and group C (mean survival, 82.1%; 95% CI, 66.0%-98.1%; P = .008). Histopathologic assessment revealed that group D again showed significantly inferior overall survival, increased cartilage necrosis, and decreased mean vessel density compared with group A. Group C additionally showed significantly decreased cartilage survival compared with group A (65% vs 0%; P < .001) and group B (65% vs 35%; P = .02). CONCLUSIONS AND RELEVANCE: These results represent preliminary evidence that the attachment of skin to perichondrium in a composite graft plays an important role for graft survival. Clinicians performing nasal reconstruction with chondrocutaneous composite grafts should consider preserving attachments at this junction to improve graft survival. LEVELS OF EVIDENCE: NA.

Post-tenure Review at U.S. Medical Schools.

PURPOSE: To assess post-tenure review policies at U.S. medical schools by examining how prevalent post-tenure review is, what models of post-tenure review are employed, and what outcomes result from post-tenure review processes. METHOD: In late 2014, a Web-based survey was sent to the associate dean for faculty affairs (or equivalent) at each U.S. medical school accredited by the Liaison Committee on Medical Education (N = 141). The survey addressed elements of post-tenure review policies, including whether a policy was in place, the frequency of the review, and the review outcomes. Descriptive statistics were calculated. RESULTS: Of the 94 responding schools with a tenure system, 39 (41%) had an established post-tenure review policy. Although these policies showed great variability across schools in duration, having been in place from 1 to 50 years, 12 (31%) were established within the last 5 years. The outcomes of post-tenure review also varied. Superior performance ratings generally resulted in notations in the faculty member's personnel file and notifications to school leadership. Conversely, when a faculty member received an unsatisfactory rating, a remediation or development plan was sometimes required. CONCLUSIONS: At least 40% of medical schools with a tenure system have post-tenure review, and it is becoming more common. These findings about the prevalence and use of post-tenure review across institutions can assist medical school leaders as they strive to shape policies to facilitate faculty engagement and productivity. They also can provide the foundation for future evaluative studies on the effectiveness, outcomes, and impact of post-tenure review.

Effect of unilateral noise exposure on the tonotopic distribution of spontaneous activity in the cochlear nucleus and inferior colliculus in the cortically intact and decorticate rat.

Effects of unilateral noise exposure on spontaneous activity (SA) in the anteroventral and dorsal cochlear nuclei (AVCN and DCN) and the central nucleus of the inferior colliculus (ICc) were studied in cortically intact and decorticate rats. SA was measured 1 week following exposure using uptake of 14C-labeled 2-deoxyglucose (2DG) in quiet. Optical density (OD) measurements were obtained in low- and high-frequency (LF and HF) areas of each nucleus. We refer to the ipsilateral AVCN and DCN (side of the noise-exposed ear) and the contralateral ICc as direct nuclei and to their opposite side counterparts as indirect nuclei. Noise exposure altered the tonotopic profile of SA in the direct pathway by causing a decrease in the ratio of HF OD to LF OD (HF/LF ratio). In intact animals, the decreased HF/LF ratio was due to decreased HF OD. In decorticate animals, it was due to decreased HF OD and increased LF OD, the latter occurring mainly in the DCN and ICc. Decorticate-intact differences may reflect corticofugal feedback inhibition. Lesion of the dorsal acoustic stria caused a substantial decrement of SA in the contralateral ICc. Furthermore, strong positive correlations between HF/LF ratios in the DCN, AVCN, and contralateral ICc suggest that the cochlear nucleus is a major contributor to SA in the ICc. Noise exposure had opposite and weaker effects on 2DG uptake in the indirect pathway that were attributed to crossed inhibition. Noise-induced changes in the tonotopic profile of SA may represent a neural correlate of tinnitus.

Effect of cochlear integrity on cochlear nucleus neuron glucose metabolism in aged adult broiler chickens.

Abrupt removal of excitatory input is devastating to post-synaptic neurons in normally functioning sensory systems. In both mammalian and avian auditory systems, abrupt temporary or permanent experimental deafferentation stimulates a cascade of changes in central auditory structures that can result in neuron death. Effects of naturally occurring progressive deafferentation on central auditory structure and function have not been fully described. Extensive naturally occurring cochlear damage is found in some aged chickens, despite their regenerative capacity, providing the opportunity to examine the effects of this type of deafferentation on the avian cochlear nucleus (nucleus magnocellularis, NM). Previous evaluation of NM oxidative metabolism using cytochrome oxidase histochemistry revealed that naturally occurring cochlear damage results in down-regulated metabolism in corresponding regions of NM. It is unknown how progressive hair cell damage and loss affects NM glucose uptake. Here, NM glucose metabolism is assessed using 2-deoxyglucose uptake as a marker for metabolic activity in the presence of normal, mildly damaged, severely damaged, and totally damaged cochlear hair cells. Results indicate that while severe and total cochlear damage significantly decrease NM oxidative metabolism, only total damage results in significantly decreased NM glucose metabolism. Results are discussed in the context of functional reorganization and trophic support.

Role of cochlear integrity in cochlear nucleus glucose metabolism and neuron number after cochlea removal in aging broiler chickens.

In the chicken auditory system, cochlear nucleus (nucleus magnocellularis, NM) neurons receive their only excitatory input from the ipsilateral cochlea. Cochlea removal (CR) results in an immediate decrease in NM neuron electrical activity, followed by death of approximately 30% of NM neurons. Previous work showed a decrease in NM activity and subsequent loss of NM neurons in all chicks. Egg layer adults showed NM neuron loss after CR, while neuron number remained stable in broiler adults. This suggested that effects of CR on NM were age- and breed-dependent. We now know that most aging egg layer chickens maintain largely normal cochleae throughout adulthood. Some exhibit cochlear damage with age. The converse is true of broiler chickens. Most aging broiler chickens display cochlear degeneration, with some maintaining normal cochlear anatomy throughout adulthood. The presence of extensive cochlear damage may alter the effect of CR on NM, leading to the described differences. Here, we examine the effect of unilateral CR on NM glucose metabolism and neuron number in 2, 30, 39, and 52 week-old broiler chickens found to have normal cochleae. Chickens with damaged cochleae were excluded. Using 2-deoxyglucose uptake to evaluate bilateral NM glucose metabolism, we found significantly decreased uptake ipsilateral to CR at each age examined. Bilateral cell counts revealed significant neuron loss ipsilateral to CR at each age examined. This suggests that NM glucose metabolism decreases and subsequent neuron death occurs in aging broiler chickens when a normal cochlea is removed. The status of the cochlea must play a role in the effect of deafferentation on NM glucose metabolism and neuron survival. The effect of CR appears to be dependent upon neither age nor breed, but upon cochlear integrity instead.

Breed-dependent susceptibility to acute sound exposure in young chickens.

Commercially available chickens fall into two categories: egg layers and broilers. Durham et al. (Hear. Res. 166 (2002) 82-95) showed that despite similar noisy living environments, cochleae of most adult broilers show extensive damage, while cochleae of adult egg layers are largely normal. This finding suggests that egg layers and broilers differ in their susceptibility to noise damage. Here, we evaluate breed differences in susceptibility to acoustic trauma. Young egg layers and broilers (10-17 weeks) were exposed to a 1500Hz pure tone (120dB SPL; 24h) and killed 24 or 72h later. Cochleae were prepared for scanning electron microscopy and photomicrographs of the cochlear surface were used to determine location and severity of damage. Cochleae were grouped based upon damage severity (moderate or severe). While location and area of damage were similar between both breeds at each recovery time, cochlear damage at 72h was more extensive than at 24h. We found no quantitative breed differences within either damage category or recovery time. However, more egg layers (25/27) than broilers (16/32) displayed severely damaged cochleae. Our findings conflict with those reported by Durham et al. (2002). Our results identify a breed-dependent difference in susceptibility to acute sound exposure, with young egg layers displaying increased sensitivity.

Predicting severity of cochlear hair cell damage in adult chickens using DPOAE input-output functions.

Distortion product otoacoustic emissions (DPOAE) were recorded from the ear canal of aged broiler chickens which have been shown to present with age-related cochlear degeneration [Hear. Res. 166 (2002) 82]. We describe the relationship between the shape of the DPOAE input-output (I/O) function and the type of hair cell damage present at and between the cochlear frequency places of the DPOAE primary tones (f1 and f2). The mid stimulus level compressive growth of the mean DPOAE I/O functions is reduced in a graded fashion relative to the severity of hair cell damage. However, individual DPOAE I/O functions within most hair cell damage groups show large variability from this characteristic. Various least squares regression models were used to predict hair cell density from indices derived from the DPOAE I/O function (area, threshold and slope). The results showed that no simple linear relationship exists between hair cell density and the DPOAE I/O function indices. Multivariate binary logistic regression used DPOAE I/O function indices to predict membership in hair cell damage groups. The logistic model revealed that DPOAE threshold can be used to predict the occurrence of severe/total hair cell damage with good specificity though poor sensitivity.

Hair cell counts in a rat model of sound damage: Effects of tissue preparation & identification of regions of hair cell loss.

Exposure to intense sound can damage or kill cochlear hair cells (HC). This loss of input typically manifests as noise induced hearing loss, but it can also be involved in the initiation of other auditory disorders such as tinnitus or hyperacusis. In this study we quantify changes in HC number following exposure to one of four sound damage paradigms. We exposed adult, anesthetized Long-Evans rats to a unilateral 16 kHz pure tone that varied in intensity (114 dB or 118 dB) and duration (1, 2, or 4 h) and sacrificed animals 2-4 weeks later. We compared two different methods of tissue preparation, plastic embedding/sectioning and whole mount dissection, for quantifying hair cell loss as a function of frequency. We found that the two methods of tissue preparation produced largely comparable cochleograms, with whole mount dissections allowing a more rapid evaluation of hair cell number. Both inner and outer hair cell loss was observed throughout the length of the cochlea irrespective of sound damage paradigm. Inner HC loss was either equal to or greater than outer HC loss. Increasing the duration of sound exposures resulted in more severe HC loss, which included all HC lesions observed in an analogous shorter duration exposure.

Conductive hearing loss results in changes in cytochrome oxidase activity in gerbil central auditory system.

Conductive hearing loss (CHL) restricts auditory input to an intact peripheral auditory system. Effects of deprivation on the central auditory system (CAS) have been debated, although a number of studies support the hypothesis that CHL can cause modification of CAS structure and function. The present study was designed to test the hypothesis that unilateral CHL results in a decrease in cytochrome oxidase (CO) activity in CAS nuclei that receive major afferent input from the affected ear. Gerbils at postnatal day 12 (P21) or 6-8 weeks underwent left unilateral CHL (malleus removal), cochlear ablation, or a sham surgical procedure. After a survival time of 48 hours or 3 weeks, animals were sacrificed and tissue was processed for cytochrome oxidase histochemistry. Optical density (OD) measurements were made from individual neurons in the anteroventral cochlear nucleus (AVCN) and from medial and lateral dendritic fields in the medial superior olivary nucleus (MSO), the lateral superior olivary nucleus, and the inferior colliculus. The width of the CO-stained neuropil in MSO was also measured as an estimate of dendritic length. OD measures were corrected to neutral areas of the brain. Cochlear ablation caused significant decreases in CO activity in left lower brainstem nuclei, particularly in adult animals. Following CHL, a significant decrease in CO activity was observed in the ipsilateral AVCN and a significant increase was observed in the contralateral AVCN. Cochlear ablation resulted in decreased width of MSO neuropil containing dendrites that receive primary input from the ablated ear. CHL resulted in a significant increase in the width of MSO neuropil on both sides of the brain in the P21 animals that survived 3 weeks but not in P21 animals that survived only 48 hours or in the adult animals. Unilateral CHL is associated with changes in CO activity in the AVCN and may affect MSO dendritic length in younger animals.

Gentamicin pharmacokinetics in the chicken inner ear.

Avians have the unique ability to regenerate cochlear hair cells that are lost due to ototoxins or excessive noise. Many methodological techniques are available to damage the hair cells for subsequent scientific study. A recent method utilizes topical application of an ototoxic drug to the round window membrane. The current study examines the pharmacokinetics of gentamicin in the inner ear of chickens following topical application to the round window membrane or a single systemic high dose given intraperitoneally. Chickens were given gentamicin topically or systemically and survived for 1, 4, 12, 24, or 120 h (controls at 4 and 120 h). Serum and perilymph samples were obtained prior to sacrifice and measured for gentamicin levels. Results revealed higher levels of gentamicin in the perilymph of topically treated chickens than systemically treated chickens, with significant amounts of gentamicin still present in both at the latest survival time of 5 days. As expected, systemically treated chickens had much higher levels of gentamicin in the serum than topically treated chickens. Advantages and disadvantages to each method of drug administration are discussed.

Avian brainstem neurogenesis is stimulated during cochlear hair cell regeneration.

Unlike mammals, adult avians are able to regenerate cochlear sensory hair cells following injury. Brainstem auditory neurons in chicken nucleus magnocellularis (NM), which receive their sole excitatory afferent input from the cochlea, were examined for evidence of mitosis during ototoxin-induced loss and regeneration of cochlear hair cells. Using tritiated thymidine as a mitotic marker in tissue processed for autoradiography and counterstained with thionin, labeled NM neurons and glia were counted from chickens killed 16 days after gentamicin or saline injections. Newly generated NM neurons were observed during cochlear hair cell regeneration. More labeled neurons were observed in the experimental chickens, but a few were also seen in the control chickens. We predicted labeled NM neurons would be found solely in the rostral high frequency region, given the gentamicin-induced high frequency cochlear hair cell loss and regeneration. However, the labeled NM neurons were located throughout the tonotopic axis of the nucleus. The total number of labeled neurons was lower than predicted. Many labeled NM glia were observed in experimental and control chickens. Labeled cells were also observed throughout the chicken brainstem and cerebellum in both experimental and control chickens, indicating great potential for CNS plasticity. Results in NM indicate the avian auditory system is capable of regenerating brainstem auditory neurons in addition to the previously well-established capability of regenerating cochlear hair cells in response to ototoxic injury. Recovery of both central and peripheral auditory components will be necessary to restore hearing damaged by noise or ototoxic drugs.

Contributions of age, cochlear integrity, and auditory environment to avian cochlear nucleus metabolism.

Most commercially raised broiler chickens display progressive cochlear degeneration with age [Hear. Res. 166 (2002) 82]. Recent work examining the effects of age and cochlear degeneration on avian cochlear nucleus (nucleus magnocellularis, NM) metabolism showed that changes in metabolic activity occur with age and cochlear damage [Hear. Res. 175 (2003) 101]. The auditory environment also differed between facilities housing young and adult birds. The relative contributions of age, cochlear degeneration, and auditory environment to these changes in NM metabolism are unknown. Using cytochrome oxidase (CO) histochemistry, NM neuron metabolism is examined in several age groups of birds under varying conditions. When normal cochlear integrity and auditory environment are held constant, CO staining is significantly decreased in adult vs. young birds. When age and auditory environment are held constant, CO staining is significantly decreased in birds with damaged vs. normal cochleae. When age and normal cochlear integrity are held constant, CO staining is significantly decreased in birds living in a quiet vs. noisy environment. All factors examined cause changes in CO staining, which is indicative of NM metabolic activity. Results are discussed in the context of mitochondrial aging, afferent regulation, and auditory deprivation and enrichment.

Breed differences in cochlear integrity in adult, commercially raised chickens.

Two types of chickens are commercially available. Broiler birds are bred to develop quickly for meat production, while egg layers are bred to attain a smaller adult size. Because we have observed breed differences in the response of central auditory neurons to cochlear ablation in adult birds [Edmonds et al. (1999) Hear. Res. 127, 62-76], we examined cochleae from the two breeds for differences in integrity. We evaluated cochlear hair cell structure using scanning electron microscopy and cochlear hair cell function using distortion product otoacoustic emissions (DPOAEs) and the auditory brainstem response. We observed striking breed differences in cochlear integrity in adult but not hatchling birds. In adult broiler birds, all cochleae showed damage, encompassing at least the basal 29% of the cochlea. In 15 of 18 broiler ears, damage was observed throughout the basal 60% of the cochlea. In contrast, cochleae from egg layer adults were largely normal. Two thirds of egg layer ears showed no anatomical abnormalities, while in the remainder cochlear damage was seen within the basal 48% of the cochlea. DPOAEs recorded from egg layer birds showed loss of high frequency emissions in every ear for which the cochlea displayed anatomical damage. Average sound pressure levels in both commercial facilities were 90 dB, suggesting these two breeds may exhibit differential susceptibility to noise damage.

Effects of age and cochlear damage on the metabolic activity of the avian cochlear nucleus.

Most aging commercially raised broiler chickens display a progressive loss of cochlear hair cells in a pattern similar to the cochlear degeneration found in aging humans: basal (high frequency) hair cells are affected first, followed by apical (low frequency) hair cells [Durham et al., Hear. Res. 166 (2002) 82-95]. Here, cochlear anatomy was assessed from scanning electron micrographs. Then, the metabolic activity of cochlear nucleus (nucleus magnocellularis, NM) neurons in 15-19, 30, 39, 40, and 65-66 week old broiler chickens was examined using cytochrome oxidase histochemistry and compared to the degree of cochlear abnormality. Cochleae of 15-19 week old birds are largely normal; therefore the level of NM metabolic activity is considered the baseline. Cochleae of the 30 week old group display mild damage and hair cell regeneration in the base. Metabolic activity in rostral (high frequency) NM is increased relative to the baseline, while activity remains unchanged in caudal (low frequency) NM. The 39 and 65-66 week old groups display severe and total damage extending into the apex of the cochlea. Metabolic activity is decreased in rostral and caudal NM at these ages. These results suggest that auditory central nervous system metabolism (cytochrome oxidase activity) is affected by changes in the aging chicken cochlea.

Time course and quantification of changes in cochlear integrity observed in commercially raised broiler chickens.

Extensive cochlear hair cell damage and loss occurs in aged broiler chickens. We describe the time course and several characteristics of this decline in cochlear integrity in 19-, 30-, 38- and 66-week-old commercially raised broiler chickens. The 19-week-old group is normal and serves as a baseline for comparison. Generally, cochlear damage increases in severity and percent length of the cochlea with age. Hair cell density increases from the base to the apex. Density is similar across the groups in regions of the cochlea that sustained little or no damage, and decreases in regions of extreme damage. Counts of normal and abnormal hair cells are inversely related. A subset of 66-week-old birds has higher density measurements and increased hair cell counts in the apical region of the cochlea. The progressive damage found in these commercially raised birds is described in the context of both the effects of age and noise exposure on the auditory system. Two additional groups of birds were raised at the University of Kansas Medical Center in a quieter environment to determine the cause of the damage seen in age-matched commercially raised birds. These cochleae are largely normal; a small number displayed damage. This suggests that noise exposure exacerbates naturally occurring cochlear degradation.