[Efficacy evaluation of 0.05% cyclosporine A and 0.1% tacrolimus eye drops in the treatment of severe dry eye associated with chronic graft-versus-host disease].

Objective: To evaluate the effectiveness and safety of 0.05% cyclosporine A and 0.1% tacrolimus eye drops in treating severe dry eye associated with chronic graft-versus-host disease (cGVHD). Methods: This non-randomized concurrent control trial enrolled 83 eyes from 83 patients with cGVHD-associated severe dry eye. The treatment had two phases. During the initial shock treatment period (0-3 months), 44 patients received 0.05% cyclosporine A eye drops (4 times/day; group A) and 39 patients received 0.1% tacrolimus eye drops (twice/day; group B) alongside basic treatment. In the maintenance treatment period (3-6 months), both groups used 0.05% cyclosporine A eye drops (twice/day) and sodium hyaluronate. Examinations were conducted at 1, 3, and 6 months after treatment initiation, assessing the Ocular Surface Disease Index (OSDI), corneal fluorescein staining (CFS) score, and fluorescein tear break-up time (BUT) for efficacy. visual acuity and intraocular pressure (IOP) were evaluated for safety, and patients' post-medication irritation symptoms were recorded. Results: The study included 52 males and 31 females, aged (28.57±15.67) years. After 1 month of treatment, the CFS score in group A significantly decreased from 10.0 (6.0, 14.0) to 5.0 (3.0, 8.5) (P<0.001). in group B, the CFS score also significantly decreased from 10.0 (6.0, 15.0) to 6.0 (2.0, 10.0), and the BUT increased from 2.0 (1.0, 2.0) s to 2.0 (1.8, 3.3) s (P<0.001). No significant OSDI decrease was observed in either group. No significant differences were found in OSDI, CFS score, and BUT between the two groups. After 3 months, group A showed significant improvement in OSDI, CFS score, and BUT (P<0.05), while group B only demonstrated significant CFS score decrease (P<0.05). OSDI was significantly lower in group A than group B (P<0.05). No significant differences were noted in CFS score and BUT between groups. After 6 months, OSDI, CFS score, and BUT were 18.9 (9.3, 34.2), 7.0 (3.0, 8.5), and 2.0 (1.0, 3.0) s in group A, and 10.9 (3.6, 35.4), 5.5 (2.8, 10.0), and 2.0 (1.0, 10.0) s in group B. In both groups, CFS scores significantly decreased and BUT increased (P<0.05). Visual acuity improved significantly in group A at 1, 3, and 6 months (P<0.05), while no significant changes were seen in group B. Irritation symptoms were transient and self-resolving in both groups. Conclusions: Both 0.05% cyclosporine A and 0.1% tacrolimus eye drops, when combined with local glucocorticoids, exhibited significant anti-inflammatory effects, effectively and safely treating severe dry eye in cGVHD patients. Although the onset of 0.05% cyclosporine A was slower than 0.1% tacrolimus, it offered more stable long-term effects and better symptom improvement.

[Two cases of airway dysfunction related to diacetyl exposure].

Occupational exposure to diacetyl can lead to bronchiolitis obliterans. In this paper, two patients with severe obstructive ventilation disorder who were exposed to diacetyl at a fragrance and flavours factory were analyzed. The clinical manifestations were cough and shortness of breath. One of them showed Mosaic shadows and uneven perfusion in both lungs on CT, while the other was normal. Field investigation found that 4 of the 8 workers in the factory were found to have obstructive ventilation disorder, and 2 had small airway dysfunction. This paper summarizes the diagnostic process of patients in order to improve the understanding of airway dysfunction caused by occupational exposure to diacetyl and promote the development of relevant standards.

Linc00601 upregulation promotes hepatocellular carcinoma development by activating MAPK signaling pathway.

OBJECTIVE: To study the expression of linc00601 in hepatocellular carcinoma (HCC) tissues and cells, and to study the biological function and downstream mechanism of linc00601 in HCC using in vitro experiments. PATIENTS AND METHODS: The expression of linc00601 in HCC was predicted via bioinformatics, and the expression of linc00601 in HCC tissues and cells was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). After interference with the expression of linc00601, the interference efficiency was determined using qRT-PCR, and the changes in HCC cell proliferation, cycle distribution, and apoptosis were determined through Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Finally, the expressions of molecular markers in downstream signaling pathway were determined through Western blotting. RESULTS: It was found via bioinformatics that the expression of linc00601 was upregulated in HCC. The results of qRT-PCR revealed that the expression of linc00601 was upregulated in 36 cases of HCC tissues compared with that in para-carcinoma tissues, and it was also upregulated in HCC cells. According to the results of CCK-8 assay, HCC cell proliferation was inhibited after interference with the expression of linc00601. In the si-linc00601 group, the apoptosis rate rose, and the cell cycle was arrested at the G1/G0 phase compared with those in the si-NC group. The results of Western blotting revealed that after the knockdown of linc00601 in HCC cells, the expressions of molecular markers (p-P38, p-ERK) in the downstream mitogen-activated protein kinase (MAPK) signaling pathway were downregulated. CONCLUSIONS: Linc00601 is upregulated in HCC, which promotes the development of HCC via activating the MAPK signaling pathway.

Toll-like receptor 4 modulates the cochlear immune response to acoustic injury.

Acoustic overstimulation traumatizes the cochlea, resulting in auditory dysfunction. As a consequence of acoustic injury, the immune system in the cochlea is activated, leading to the production of inflammatory mediators and the infiltration of immune cells. However, the molecular mechanisms responsible for initiating these immune responses remain unclear. Here, we investigate the functional role of Toll-like receptor 4 (Tlr4), a cellular receptor that activates the innate immune system, in the regulation of cochlear responses to acoustic overstimulation. Using a Tlr4 knockout mouse model, we examined how Tlr4 deficiency affects sensory cell pathogenesis, auditory dysfunction and cochlear immune activity. We demonstrate that Tlr4 knockout does not affect sensory cell viability under physiological conditions, but reduces the level of sensory cell damage and cochlear dysfunction after acoustic injury. Together, these findings suggest that Tlr4 promotes sensory cell degeneration and cochlear dysfunction after acoustic injury. Acoustic injury provokes a site-dependent inflammatory response in both the organ of Corti and the tissues of the lateral wall and basilar membrane. Tlr4 deficiency affects these inflammatory responses in a site-dependent manner. In the organ of Corti, loss of Tlr4 function suppresses the production of interleukin 6 (Il6), a pro-inflammatory molecule, after acoustic injury. By contrast, the production of inflammatory mediators, including Il6, persists in the lateral wall and basilar membrane. In addition to immune molecules, Tlr4 knockout inhibits the expression of major histocompatibility complex class II, an antigen-presenting molecule, in macrophages, suggesting that Tlr4 participates in the antigen-presenting function of macrophages after acoustic trauma. Together, these results suggest that Tlr4 regulates multiple aspects of the immune response in the cochlea and contributes to cochlear pathogenesis after acoustic injury.

Activation of the antigen presentation function of mononuclear phagocyte populations associated with the basilar membrane of the cochlea after acoustic overstimulation.

The immune response is an important component of the cochlear response to stress. As an important player in the cochlear immune system, the basilar membrane immune cells reside on the surface of the scala tympani side of the basilar membrane. At present, the immune cell properties in this region and their responses to stress are not well understood. Here, we investigated the functional role of these immune cells in the immune response to acoustic overstimulation. This study reveals that tissue macrophages are present in the entire length of the basilar membrane under steady-state conditions. Notably, these cells in the apical and the basal sections of the basilar membrane display distinct morphologies and immune protein expression patterns. Following acoustic trauma, monocytes infiltrate into the region of the basilar membrane, and the infiltrated cells transform into macrophages. While monocyte infiltration and transformation occur in both the apical and the basal sections of the basilar membrane, only the basal monocytes and macrophages display a marked increase in the expression of major histocompatibility complex (MHC) II and class II transactivator (CIITA), a MHC II production cofactor, suggesting the site-dependent activation of antigen-presenting function. Consistent with the increased expression of the antigen-presenting proteins, CD4(+) T cells, the antigen-presenting partner, infiltrate into the region of the basilar membrane where antigen-presenting proteins are upregulated. Further pathological analyses revealed that the basal section of the cochlea displays a greater level of sensory cell damage, which is spatially correlated with the region of antigen-presenting activity. Together, these results suggest that the antigen-presenting function of the mononuclear phagocyte population is activated in response to acoustic trauma, which could bridge the innate immune response to adaptive immunity.

Transcriptome characterization by RNA-Seq reveals the involvement of the complement components in noise-traumatized rat cochleae.

Acoustic trauma, a leading cause of sensorineural hearing loss in adults, induces a complex degenerative process in the cochlea. Although previous investigations have identified multiple stress pathways, a comprehensive analysis of cochlear responses to acoustic injury is still lacking. In the current study, we used the next-generation RNA-sequencing (RNA-Seq) technique to sequence the whole transcriptome of the normal and noise-traumatized cochlear sensory epithelia (CSE). CSE tissues were collected from rat inner ears 1d after the rats were exposed to a 120-dB (sound pressure level) noise for 2 h. The RNA-Seq generated over 176 million sequence reads for the normal CSE and over 164 million reads for the noise-traumatized CSE. Alignment of these sequences with the rat Rn4 genome revealed the expression of over 17,000 gene transcripts in the CSE, over 2000 of which were exclusively expressed in either the normal or noise-traumatized CSE. Seventy-eight gene transcripts were differentially expressed (70 upregulated and 8 downregulated) after acoustic trauma. Many of the differentially expressed genes are related to the innate immune system. Further expression analyses using quantitative real time PCR confirmed the constitutive expression of multiple complement genes in the normal organ of Corti and the changes in the expression levels of the complement factor I (Cfi) and complement component 1, s subcomponent (C1s) after acoustic trauma. Moreover, protein expression analysis revealed strong expression of Cfi and C1s proteins in the organ of Corti. Importantly, these proteins exhibited expression changes following acoustic trauma. Collectively, the results of the current investigation suggest the involvement of the complement components in cochlear responses to acoustic trauma.

Differential expression of apoptosis-related genes in the cochlea of noise-exposed rats.

Exposure to intense noise induces apoptosis in hair cells in the cochlea. To identify the molecular changes associated with noise-induced apoptosis, we used quantitative real-time PCR to evaluate the changes in 84 apoptosis-related genes in cochlear samples from the sensory epithelium and lateral wall. Sprague-Dawley rats exposed to a continuous noise at 115 dB SPL for 2 h. The exposure caused a 40-60 dB threshold shift 4 h post-exposure that decreased to 20-30 dB 7 days post-exposure. These functional changes were associated with apoptotic markers including nuclear condensation and fragmentation and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Immediately after the noise exposure, 12 genes were downregulated, whereas only one gene (Traf4) was upregulated. At 4 h post-exposure, eight genes were upregulated; three (Tnrsf1a, Tnfrsf1b, Tnfrst5) belonged to the Tnfrsf family, three (Bir3, Mcl1 and Prok2) have anti-apoptotic properties and one (Gadd45a) is a target of p53. At 7 days post-exposure, all the upregulated genes returned to pre-noise levels. Interestingly, the normal control cochlea had high constitutive levels of several apoptosis-related genes. These constitutively expressed genes, together with the inducible genes, may participate in the induction of cochlear apoptotic activity.

Enzymatically cross-linked hydrogels and their adhesive strength to biosurfaces.

OBJECTIVES: To design an in-situ gelling hydrogel capable of solidifying rapidly under physiologic conditions into a hydrogel capable of adhering tissue surfaces together. DESIGN: Multifunctional polymers containing covalently bound peptide substrates of transglutaminase were designed. EXPERIMENTAL VARIABLE: Enzyme cross-linked hydrogels were compared with commercial fibrin tissue adhesive. OUTCOME MEASURE: The shear strength between tissue surfaces or type 1 collagen membranes bonded with hydrogel was measured. RESULTS: The shear adhesive strength of transglutaminase cross-linked hydrogels was found to be equal to or better than fibrin sealant for tissue and collagen surfaces, respectively. CONCLUSION: Transglutaminase cross-linked hydrogels are injectable, in-situ formed, biodegradable, and expected to be useful in a variety of applications including sustained drug delivery, medical and dental adhesives, tissue repair and engineering as polymeric scaffolds, and gene therapy.

Intense noise-induced apoptosis in hair cells of guinea pig cochleae.

Cells can die by two distinct pathways: apoptosis and necrosis. To explore whether intense noise can induce hair cell (HC) death via the apoptotic pathway, we systematically examined morphological changes in guinea pig cochlear HC nuclei stained with Hoechst 33342, a fluorescent dye specifically labelling the nuclear DNA. A narrow band noise centred at 4 kHz with levels at 110 dB, 115 dB or 120 dB (SPL) was applied for 4 h and the exposed cochleae were collected at various intervals (3 h, 3 or 14 days) after the noise exposure. Auditory function was monitored by measuring thresholds of auditory brain stem responses. In the noise-damaged cochleae, there were two major types of nuclear changes, nuclear condensation appeared as karyorrhexis or karyopyknosis and nuclear swelling. Karyorrhexis and karyopyknosis predominately appeared in the severely damaged cochlear region in the animals exposed to 120 dB noise and examined 3 h after the noise exposure. In contrast, swelling of nuclei occurred in all of the noise-exposed cochleae, and was the feature change in the animals exposed to 110 and 115 dB noise. This pathological change persisted at least for 14 days after the noise exposure. The typical changes of karyorrhexis and karyopyknosis noted in the animals exposed to 120 dB noise were morphologically similar to those nuclear changes described in previous studies for apoptosis, suggesting that the apoptotic process may be involved in intense noise-induced HC death.

The role of glutathione in carboplatin ototoxicity in the chinchilla.

The role of glutathione in carboplatin ototoxicity was investigated in the chinchilla. Chinchillas hearing was tested with both distortion product otoacoustic emissions (DPOAE) and evoked potentials recorded from a chronic electrode in the inferior colliculus (IC). All subjects had an osmotic pump fitted to their right ear and it received buthionine sulfoximine (BSO) at a dose of 15 mM delivered at 5 ml per hour for 14 days. A group (N=4) was given a double dose of carboplatin (25 mg/kg i.p. for 2 days). The pump was implanted three days before the carboplatin dose. The BSO treated ears showed a greater loss in both evoked potential and DPOAE measures, as well as substantially fewer missing hair cells. The results implicate reactive oxygen species (ROS) as a common factor in ototoxic reactions because suppression of glutathione antioxidant leads to greater ototoxic reactions.

Intracochlear infusion of buthionine sulfoximine potentiates carboplatin ototoxicity in the chinchilla.

The aim of this experiment was to determine if buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, enhances the ototoxicity of carboplatin. Osmotic pumps were used to infuse BSO into the right cochleas of 12 adult chinchillas for 14 days. The left cochleas served as controls. Animals were assigned to three groups: a drug control group that did not receive carboplatin, a group that received a single dose of carboplatin (25 mg/kg i.p.), and a group that received a double dose of carboplatin (25 mg/kg i.p. x 2), with 4 days between injections. Carboplatin was administered after three days of BSO pre-treatment. Ototoxicity was assessed with evoked potentials recorded from electrodes implanted in the inferior colliculi (ICPs), distortion product otoacoustic emissions (DPOAEs), and cochleograms. BSO infusion itself caused no long-term functional or morphological changes. One of four animals treated with it single dose of carboplatin showed a significant loss of inner hair cells (IHCs), with greater loss in the BSO-treated ear. All animals in the double-dose carboplatin group showed marked differences between BSO-treated and control ears. Average IHC losses were 59% in BSO-treated ears vs. 18% in control ears. Moreover, BSO-treated ears sustained significantly greater outer hair cell (OHC) losses than control ears (37% vs. 2%, respectively). ICP and DPOAE response amplitudes were reduced slightly in BSO-treated ears relative to control ears, consistent with their greater hair cell loss. The results clearly show that BSO can enhance carboplatin ototoxicity in the chinchilla, supporting a role of GSH and reactive oxygen species in platinum ototoxicity.

Age- and strain-related differences in dehydrogenase activity and glycogen levels in CBA and C57 mouse cochleas.

In the C57 mouse strain, loss of sensory hair cells (HCs) begins during early adulthood, starting in the base of the cochlea and progressing toward the apex as aging continues. In contrast, the CBA mouse strain exhibits no significant cochlear histopathology until relatively late in life. These strain and age differences may be related to differences in cochlear energy metabolism. To examine this possibility, we used dehydrogenase and glycogen histochemistry to evaluate the metabolic capacities of HCs and stria vascularis (SV) in cochleas of C57 and CBA mice. Reaction product density was quantified and compared as a function of strain (1.5-month-old C57 mice vs. CBA mice) and age (CBA mice, 1.5, 18 and 36 months). Young C57 mice had significantly less HC dehydrogenase activity than CBA mice of any age, lower HC glycogen levels than 18-month-old CBA mice and lower SV glycogen levels than 18- or 36-month-old CBA animals. Within the CBA strain, HC dehydrogenase activity decreased significantly between 1.5 and 18 months of age, while glycogen levels in both HCs and SV increased over the same time period. Between 18 and 36 months, HC dehydrogenase activity and SV glycogen levels remained stable. The results show that there are significant age-related changes in energy metabolism in the inner ear of CBA mice that are correlated with age-related hearing loss. Genetically determined deficits in cochlear metabolic capacity in C57 mice could be linked to the early onset of hearing loss in this strain.

Selective loss of inner hair cells and type-I ganglion neurons in carboplatin-treated chinchillas. Mechanisms of damage and protection.

Carboplatin preferentially destroys inner hair cells (IHCs) and type-I spiral ganglion neurons while sparing outer hair cells (OHCs). Loss of IHCs and type-I ganglion cells is associated with a significant reduction of the compound action potential (CAP). However, the cochlear microphonic (CM) potential and distortion product otoacoustic emissions (DPOAEs) remain normal, indicating that the OHCs are functionally intact. In the vestibular system, carboplatin selectively destroys type-I hair cells and their afferent neurons. Damage of type-I vestibular hair cells and their afferent terminals is associated with significant depression of nystagmus induced by cold, caloric stimulation. Histochemical studies revealed a rapid decrease in succinate dehydrogenase (SDH) staining in IHCs soon after carboplatin treatment, and staining intensity remained depressed in surviving IHCs for at least 1 month after carboplatin treatment. These results suggest that carboplatin depresses the metabolic function in surviving IHCs. Several lines of evidence suggest that free radicals may contribute to carboplatin-induced sensory cell damage. Intracochlear infusion of L-buthionine-[S,R]-sulfoximine (BSO), which depletes intracellular glutathione (GSH), increases IHC and OHC loss. Previous in vitro studies have shown that neurotrophin 4/5 (NT-4/5) promotes the survival of spiral ganglion neurons from cisplatin ototoxicity. In vivo perfusion of NT-4/5 promoted the survival of spiral ganglion neurons, but did not protect the hair cells.

R-phenylisopropyladenosine attenuates noise-induced hearing loss in the chinchilla.

Reactive oxygen species, which are cytotoxic to living tissues, are thought to be partly responsible for noise-induced hearing loss. In this study R-phenylisopropyladenosine (R-PIA), a stable non-hydrolyzable adenosine analogue which has been found effective in upregulating antioxidant enzyme activity levels, was topologically applied to the round window of the right ears of chinchillas. Physiological saline was applied to the round window of the left ears (control). The animals were then exposed to a 4 kHz octave band noise at 105 dB SPL for 4 h. Inferior colliculus evoked potential thresholds and distortion product otoacoustic emissions (DPOAE) were measured and hair cell damage was documented. The mean threshold shifts immediately after the noise exposure were 70-90 dB at frequencies between 2 and 16 kHz. There were no significant differences in threshold shifts at this point between the R-PIA-treated and control ears. By 4 days after noise exposure, however, the R-PIA-treated ears showed 20-30 dB more recovery than saline-treated ears at frequencies between 4 and 16 kHz. More importantly, threshold measurements made 20 days after noise exposure showed 10-15 dB less permanent threshold shifts in R-PIA-treated ears. The amplitudes of DPOAE also recovered to a greater extent and outer hair cell losses were less severe in the R-PIA-treated ears. The results suggest that administration of R-PIA facilitates the recovery process of the outer hair cell after noise exposure.

Changes in F-actin labeling in the outer hair cell and the Deiters cell in the chinchilla cochlea following noise exposure.

It has been found that 'conditioning' noise exposures can render the inner ear more resistant to traumatic noise exposures. To explore the possible mechanisms underlying this phenomenon, filamentous actin (F-actin), labeled by rhodamine-phalloidin, was examined in the chinchilla cochlea using confocal fluorescence microscopy. The conditioning noise was 0.5 kHz octave band noise (OBN) at 90 dB SPL for 6 h/day and the high-level noise was the same noise but at 105 dB SPL for 4 h. A variety of pathological changes were found in the chinchilla cochlea after exposure to noise. Subjects exposed to conditioning noise (1 day or 10 days) and only high-level noise showed an increase in F-actin labeling than unexposed controls. By contrast, subjects who had 5 days quiet after the 10-day conditioning exposure exhibited a decrease in F-actin labeling. Interestingly, subjects exposed to high-level noise with prior 10-day conditioning exposure also showed a decrease in F-actin labeling in the cuticular plate and the stereocilia. The F-actin decreases in the stereocilia and the cuticular plates may decrease the mechanical rigidity of the organ of Corti. A more pliable organ of Corti may have reduced the possibility of fracture or ripping of cell junctions during the motion of the basilar membrane induced by acoustic overstimulation.

The influence of the cochlear efferent system on chronic acoustic trauma.

The role of the olivocochlear bundle (OCB) in modulating noise-induced permanent injury to the auditory periphery was studied by completely sectioning the OCB fibers in chinchillas and exposing the animals while awake to a broad-band noise at 105 dB SPL for 6 h. Outer hair cell (OHC) function was assessed by measuring 2f1-f2 distortion product otoacoustic emissions (DPOAE) at frequencies from 1.2 to 9.6 kHz and cochlear microphonics (CM) at frequencies from 1 to 8 kHz. As a result of de-efferentation, the CM was decreased but the DPOAEs were unchanged in de-efferented ears as compared with efferented control and sham-operated ears. Following noise exposure, the ears that were de-efferented showed significantly more depression of DPOAE input/output functions and greater decrement of CM amplitude. The differences between de-efferented and efferent-innervated ears were evident across all the frequencies. The cochlear lesions of the OHCs reflected by traditional cytocochleograms, however, were minimal in both efferented and de-efferented ears. The results indicate that cochlear de-efferentation decreases the CM in chinchilla and increases the ear's susceptibility to noise-induced permanent hearing damage. More importantly, de-efferentation increases susceptibility at low frequencies as well as high frequencies.

[Isoflavones from Glycyrrhiza eurycarpa].

A new isoflavone, named eurycarpin A and a new natural product isoflavone named eurycarpin B have been isolated from the roots of Glycyrrhiza eurycarpa P. C. Li. Their structures were determined to be 7,2',4'-trihydroxy-3'-(3,3-dimethylallyl) isoflavone(I) and 7,2'-dihydroxy-6",6"-dimethylpyrano-(2",3":4',3') isoflavone(II) on the basis of spectroscopic analysis (UV, EI-MS, 1HNMR, 13CNMR, NOE difference and HMBC). In addition, three known isoflavones, licoisoflavone A, calycosin and formononetin, were obtained for the first time from this plant.

Recovery of structure and function of inner ear afferent synapses following kainic acid excitotoxicity.

The present study was conducted to examine the re-establishment of IHC/VIII nerve synapses following kainic acid (KA) excitotoxicity and to discern if the re-organized afferent could render not only a normal auditory threshold but also a normal supra-threshold function. KA (60 mM) applied to the intact round window membrane in chinchilla destroyed postsynaptic endings of the auditory nerve, depressed the input-output (I/O) functions of auditory evoked potentials (EVP) and produced an average loss of sensitivity of over 80 dB at 4, 8, and 16 kHz, with less substantial losses (40-60 dB) at lower frequencies. However, there was no significant difference in 2f1-f2 distortion-product otoacoustic emissions (DPOAE) before and after the application of KA. The nerve endings went through a sequence of swelling, degeneration and recovery over a 3-5 day period at higher frequency. Auditory sensitivity and supra-threshold response returned accordingly. In contrast, complete recovery at lower frequencies (1 and 2 kHz) required more than 5 days. The results provide strong evidence that (1) excitotoxically damaged cochlear afferent neurons can recover and render both a normal EVP threshold and EVP I/O function and (2) afferent innervation to IHCs is not necessary for DPOAE generation.

The role of the cochlear efferent system in acquired resistance to noise-induced hearing loss.

Previous work has shown that the cochlear efferent system may play a role in protecting the ear from noise-induced temporary threshold shifts (TTS) following exposures to a single tone or series of moderate-level noises ('toughening'). However, whether the olivocochlear bundle (OCB) is important in decreasing noise-induced permanent threshold shifts (PTS) remains an open question. The importance of the OCB in decreasing the ear's susceptibility to noise, as reflected by 2f1-f2 distortion product otoacoustic emissions, was assessed by sectioning both the ipsilateral and contralateral divisions of the efferent system and exposing chinchillas while awake to an octave band noise (4 kHz) at a low level (85 dB SPL) for 10 days (6 h/day) and then at a high level (95 dB SPL) for 48 h. Complete de-efferentation was verified by cochlear acetylcholinesterase staining. The ears that were de-efferent showed substantially more TTS, greater PTS and larger cochlear lesions of outer hair cells. The results suggest that the efferent system may influence the ear's ability to develop resistance to noise trauma.