Three-dimensional mouse cochlea imaging based on the modified Sca/eS using confocal microscopy.

The three-dimensional stria vascularis (SV) and cochlear blood vessel structure is essential for inner ear function. Here, modified Sca/eS, a sorbitol-based optical-clearing method, was reported to visualize SV and vascular structure in the intact mouse cochlea. Cochlear macrophages as well as perivascular-resident macrophage-like melanocytes were detected as GFP-positive cells of the CX3CR1+/GFP mice. This study's method was effective in elucidating inner ear function under both physiological and pathological conditions.

The disruption and hyperpermeability of blood-labyrinth barrier mediates cisplatin-induced ototoxicity.

The ototoxic mechanisms of cisplatin on the organ of Corti and spiral ganglion neurons have been extensively studied, while few studies have been focused on the stria vascularis (SV). Herein, we verified the functional and morphological impairment in SV induced by a single injection of cisplatin (12 mg/kg, I.P.), represented by a reduction in Endocochlear Potentials (EP) and strial atrophy, and explored underlying mechanisms. Our results revealed increased extravasation of chromatic tracers (Evans blue dye and FITC-dextran) around microvessels after cisplatin exposure. The increased vascular permeability could be attributed to changes of pericytes (PCs) and perivascular-resident macrophage-like melanocytes (PVM/Ms) in number or morphology, as well as the enhanced level of HIF-1α and downstream VEGF. This capillary leakage led to a high accumulation of cisplatin in the perivascular space in SV, and disrupted the integrity of blood-labyrinth barrier (BLB). Also, tight junction (ZO-1) loosening and Na+, K+-ATPase damage was considered to be other critical contributors of BLB breakdown, which resulted in EP drop and consequent hearing loss. This study explored the role of stria vascularis in cisplatin-induced ototoxicity in terms of BLB hyperpermeability and pointed to a novel therapeutic target for the prevention of cisplatin-related hearing loss.

Hearing Impairment in a Mouse Model of Diabetes Is Associated with Mitochondrial Dysfunction, Synaptopathy, and Activation of the Intrinsic Apoptosis Pathway.

Although previous studies continuously report an increased risk of hearing loss in diabetes patients, the impact of the disease on the inner ear remains unexplored. Herein, we examine the pathophysiology of diabetes-associated hearing impairment and cochlear synaptopathy in a mouse model of diabetes. Male B6.BKS(D)-Leprdb/J (db/db, diabetes) and heterozygote (db/+, control) mice were assigned into each experimental group (control vs. diabetes) based on the genotype and tested for hearing sensitivity every week from 6 weeks of age. Each cochlea was collected for histological and biological assays at 14 weeks of age. The diabetic mice exerted impaired hearing and a reduction in cochlear blood flow and C-terminal-binding protein 2 (CtBP2, a presynaptic ribbon marker) expression. Ultrastructural images revealed severely damaged mitochondria from diabetic cochlea accompanied by a reduction in Cytochrome c oxidase subunit 4 (COX4) and CR6-interacting factor 1 (CRIF1). The diabetic mice presented significantly decreased levels of platelet endothelial cell adhesion molecule (PECAM-1), B-cell lymphoma 2 (BCL-2), and procaspase-9, but not procaspase-8. Importantly, significant changes were not found in necroptotic programmed cell death markers (receptor-interacting serine/threonine-protein kinase 1, RIPK1; RIPK3; and mixed lineage kinase domain-like pseudokinase, MLKL) between the groups. Taken together, diabetic hearing loss is accompanied by synaptopathy, microangiopathy, damage to the mitochondrial structure/function, and activation of the intrinsic apoptosis pathway. Our results imply that mitochondrial dysfunction is deeply involved in diabetic hearing loss, and further suggests the potential benefits of therapeutic strategies targeting mitochondria.

VEGFA165 gene therapy ameliorates blood-labyrinth barrier breakdown and hearing loss.

Millions of people are affected by hearing loss. Hearing loss is frequently caused by noise or aging and often associated with loss of pericytes. Pericytes populate the small vessels in the adult cochlea. However, their role in different types of hearing loss is largely unknown. Using an inducible and conditional pericyte depletion mouse model and noise-exposed mouse model, we show that loss of pericytes leads to marked changes in vascular structure, in turn leading to vascular degeneration and hearing loss. In vitro, using advanced tissue explants from pericyte fluorescence reporter models combined with exogenous donor pericytes, we show that pericytes, signaled by VEGF isoform A165 (VEGFA165), vigorously drive new vessel growth in both adult and neonatal mouse inner ear tissue. In vivo, the delivery of an adeno-associated virus serotype 1-mediated (AAV1-mediated) VEGFA165 viral vector to pericyte-depleted or noise-exposed animals prevented and regenerated lost pericytes, improved blood supply, and attenuated hearing loss. These studies provide the first clear-cut evidence that pericytes are critical for vascular regeneration, vascular stability, and hearing in adults. The restoration of vascular function in the damaged cochlea, including in noise-exposed animals, suggests that VEGFA165 gene therapy could be a new strategy for ameliorating vascular associated hearing disorders.

Lipopolysaccharide decreases cochlear blood flow dose dependently in a guinea pig animal model via TNF signaling.

OBJECTIVE: To evaluate the effect of Lipopolysaccharide (LPS), a bacterial endotoxin on cochlear microcirculation, and its mode of action. METHODS: Twenty-five Dunkin-Hartley guinea pigs were divided into five groups of five animals each. After surgical preparation, cochlear microcirculation was quantified by in vivo fluorescence microscopy. Placebo or LPS (1 mg, 10 µg, and 100 ng) was applied topically, and microcirculation was measured before and twice after application. A fifth group was pretreated with etanercept, a tumor necrosis factor (TNF) antagonist, and afterward the lowest LPS concentrations that yielded significant results (10 µg) were applied. RESULTS: In the groups that had been treated with 1 mg and 10 µg LPS, a significant drop in cochlear microcirculation was observed after 30 (.791 ± .089 Arbitrary Units (AU), compared to baseline, and .888 ± .071AU) and 60 (.756 ± .101 AU and .817 ± .124 AU, respectively) minutes. The groups that had been treated with 100 ng LPS and that had been pretreated with etanercept showed no significant change in cochlear blood flow compared to placebo. CONCLUSION: Lipopolysaccharide shows a dose-dependent effect on cochlear microcirculation; this effect can already be observed after 30 min. Pretreatment with etanercept can abrogate this effect, indicating that TNF mediates the effect of LPS on cochlear microcirculation.

Protective Effects of Adiponectin against Cobalt Chloride-Induced Apoptosis of Smooth Muscle Cells via cAMP/PKA Pathway.

Adiponectin (APN) is an adipokine secreted from adipose tissue and exhibits biological functions such as microcirculation-regulating, hearing-protective, and antiapoptotic. However, the effect of APN on the apoptosis of spiral arterial smooth muscle cells (SMCs) under hypoxic conditions in vitro is not clear. We used cobalt chloride (CoCl2) to simulate chemical hypoxia in vitro, and the SMCs were pretreated with APN and then stimulated with CoCl2. The viability of cells and apoptosis were assessed by CCK-8 and flow cytometry, respectively. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, cAMP level, and the activity of PKA were detected by ELISA. Protein expression and localization were studied by Western blot and immunofluorescence analysis. In the present study, we found that APN exhibits antiapoptosis effects. CoCl2 exhibited decreased cell viability, increased apoptosis and MDA levels, and decreased SOD activity in a concentration-dependent manner, compared with the control group. Moreover, CoCl2 upregulated the expression levels of Bax and cleaved caspase-3 and then downregulated Bcl-2 levels in a time-dependent manner. Compared with the CoCl2 group, the group pretreated with APN had increased cell viability, SOD activity, PKA activity, cAMP level, and PKA expression, but decreased MDA levels and apoptosis. Lastly, the protective effect of APN was blocked by cAMP inhibitor SQ22536 and PKA inhibitor H 89. These results showed that APN protected SMCs against CoCl2-induced hypoxic injury via the cAMP/PKA signaling pathway.

Acoustic Trauma Causes Cochlear Pericyte-to-Myofibroblast-Like Cell Transformation and Vascular Degeneration, and Transplantation of New Pericytes Prevents Vascular Atrophy.

Acoustic trauma disrupts cochlear blood flow and damages sensory hair cells. Damage and regression of capillaries after acoustic trauma have long been observed, but the underlying mechanism of pathology has not been understood. We show herein that loud sound causes change of phenotype from neural/glial antigen 2 positive/α-smooth muscle actin negative to neural/glial antigen 2 positive/α-smooth muscle actin positive in some pericytes (PCs) on strial capillaries that is strongly associated with up-regulation of transforming growth factor-ß1. The acoustic trauma also reduced capillary density and increased deposition of matrix proteins, particularly in the vicinity of transformed PCs. In a newly established in vitro three-dimensional endothelial cell (EC) and PC co-culture model, transformed PCs induced thicker capillary-like branches in ECs and increased collagen IV and laminin expression. Transplantation of exogenous PCs derived from neonatal day 10 mouse cochleae to acoustic traumatized cochleae, however, significantly attenuated the decreased vascular density in the stria. Transplantation of PCs pretransfected with adeno-associated virus 1-vascular endothelial growth factor-A165 under control of a hypoxia-response element markedly promotes vascular volume and blood flow, increased proliferation of PCs and ECs, and attenuated loud sound-caused loss in endocochlear potential and hearing. Our results indicate that loud sound-triggered PC transformation contributes to capillary wall thickening and regression, and young PC transplantation effectively rehabilitates the vascular regression and improves hearing.

Surgical Anatomy of the Labyrinthine and Subarcuate Arteries and Clinical Implications.

OBJECTIVE: To study the surgical anatomy of the labyrinthine artery (LA) and the subarcuate artery (SA), their anatomic relationships, and clinical implications, as injury of the LA can result in hearing loss. METHODS: Ten formalin-fixed, latex-colored specimens were studied (20 sides). After retrosigmoid craniotomy and neurovascular dissection under microscopic magnification, 4-mm 0° and 30° endoscopic lenses were used to improve visualization. Results were statistically analyzed. RESULTS: The LA was a constant artery that followed the vestibulocochlear nerve into the internal auditory canal. The SA was an inconstant artery that ended in the dura mater around the subarcuate fossa in 35% of cases. The LA originated from the anterior inferior cerebellar artery in 89.3% of specimens and from the basilar artery in 10.7% of specimens. The SA branched off from the anterior inferior cerebellar artery when present. The origin of the LA was inferomedial to the vestibulocochlear nerve in most cases (71.4%), whereas the SA was usually lateral (70%). The distal portion of the LA was inferomedial to the vestibulocochlear nerve in 71.4% of cases. The distal portion of the SA was superolateral to the nerve in all cases (P < 0.00001). CONCLUSIONS: Knowledge of the different trajectory and anatomic relationship of the LA and the SA with the vestibulocochlear nerve is of paramount importance to differentiate them during surgery. The LA is usually inferomedial to the vestibulocochlear nerve at its distal and proximal aspects, whereas the SA usually originates lateral and ends superolateral to the nerve.

Lipopolysaccharide disrupts the cochlear blood-labyrinth barrier by activating perivascular resident macrophages and up-regulating MMP-9.

OBJECTIVE: To determine the distribution of perivascularresident macrophages (PVMs) in BLB and their relationship with capillaries, and to explore the possible mechanisms responsible for lipopolysaccharide (LPS)-induced activation of PVMs and the breakdown of BLB. METHODS: Adult Balb/c mice were either trans-tympanically injected with LPS, or mock-treated. Auditory brainstem response was tested before and 48 h after treatments. Distribution of pericytes, PVMs and capillaries was analyzed by immunohistochemical staining, and BLB permeability was estimated by FITC-dextran leakage assay. Ultrastructure of stria vascularis was examined by transmission electron microscope. Protein and mRNA level of matrix metallopeptidase 9 (MMP-9), zona occludens-1 (ZO-1), interleukin-33 (IL-33) and its receptor suppression of tumorigenicity 2 (ST2) was measured by IHC and qRT-PCR. RESULTS: Unlike pericytes that surround one capillary, PVMs branched to connect with more than one capillary. LPS caused hearing loss in mice. Following LPS challenge, cochleae showed vascular leakage in stria vascularis, and PVMs presented morphological changes including reduced contact with capillaries. TEM revealed a reduced number of tight junction contact points between endothelial cells and a wider space between PVMs, pericytes and endothelial cells. The mRNA and protein levels of MMP-9 and ST2 in stria vascularis were up-regulated, while ZO-1 were down-regulated after exposure to LPS. CONCLUSIONS: Our results suggest that PVMs may play a more significant role than pericytes in maintaining the integrity of BLB. Our findings also reveal a possible mechanism contributing to LPS-induced activation of PVMs, breakdown of BLB and hearing loss.

Vascular regeneration in adult mouse cochlea stimulated by VEGF-A165 and driven by NG2-derived cells ex vivo.

Can damaged or degenerated vessels be regenerated in the ear? The question is clinically important, as disruption of cochlear blood flow is seen in a wide variety of hearing disorders, including in loud sound-induced hearing loss (endothelial injury), ageing-related hearing loss (lost vascular density), and genetic hearing loss (e.g., Norrie disease: strial avascularization). Progression in cochlear blood flow (CBF) pathology can parallel progression in hair cell and hearing loss. However, neither new vessel growth in the ear, nor the role of angiogenesis in hearing, have been investigated. In this study, we used an established ex vivo tissue explant model in conjunction with a matrigel matrix model to demonstrate for the first time that new vessels can be generated by activating a vascular endothelial growth factor (VEGF-A) signal. Most intriguingly, we found that the pattern of the newly formed vessels resembles the natural 'mesh pattern' of in situ strial vessels, with both lumen and expression of tight junctions. Sphigosine-1-phosphate (S1P) in synergy with VEGF-A control new vessel size and growth. Using transgenic neural/glial antigen 2 (NG2) fluorescent reporter mice, we have furthermore discovered that the progenitors of "de novo" strial vessels are NG2-derived cells. Taken together, our data demonstrates that damaged strial microvessels can be regenerated by reprogramming NG2-derived angiogenic cells. Restoration of the functional vasculature may be critical for recovery of vascular dysfunction related hearing loss.

The role of monocytes and macrophages in the dynamic permeability of the blood-perilymph barrier.

The blood-perilymph barrier serves a critical role by separating the components of blood from inner ear fluids, limiting traffic of cells, proteins and other solutes into the labyrinth, and allowing gas (O2-CO2) exchange. Inflammation produces changes in the blood-perilymph barrier resulting in increased vascular permeability. It is commonly thought that compromise of the blood-inner ear barrier would lead to hearing impairment through loss of the endocochlear potential (EP). In fact, the effect of increasing cochlear vascular permeability on hearing function and EP is poorly understood. We used a novel method to measure the integrity of the blood-perilymph barrier and demonstrated the effects of barrier compromise on ABR threshold and EP. We also investigated the contribution of CX3CR1 cochlear macrophages and CCR2 inflammatory monocytes to barrier function after systemic exposure to lipopolysaccharide (LPS). We found that systemic LPS induced a profound change in vascular permeability, which correlated with minimal change in ABR threshold and EP. Macrophage depletion using CX3CR1-DTR mice did not alter the baseline permeability of cochlear vessels and resulted in preservation of barrier function in LPS-treated animals. We conclude that cochlear macrophages are not required to maintain the barrier in normal mice and activated macrophages are a critical factor in breakdown of the barrier after LPS. CCR2 null mice demonstrated that LPS induction of barrier leakiness occurs in the absence of CCR2 expression. Thus, enhanced aminoglycoside ototoxicity after LPS can be linked to the expression of CCR2 in inflammatory monocytes, and not to preservation of the blood-perilymph barrier in CCR2 knockout mice.

Pathophysiology of sensorineural hearing loss in jugular foramen paraganglioma.

OBJECTIVES/HYPOTHESIS: Pathologic involvement of the inferior cochlear vein is a mechanism of sensorineural hearing loss in patients with jugular foramen paraganglioma. STUDY DESIGN: Retrospective case-control study. METHODS: The presenting audiograms, magnetic resonance imaging, and computed tomography were reviewed in 46 subjects with jugular foramen paragangliomas. Four-frequency bone conduction average was compared between the tumor and nontumor ears in each subject to establish the presence of sensorineural hearing loss. Imaging findings for each subject were recorded. Univariate and multivariate statistical analyses were performed to determine which radiographic features were associated with sensorineural hearing loss. Hearing data were analyzed as a continuous variable and as a categorical variable. RESULTS: Twenty subjects (43.4%) had a bone-conduction pure-tone asymmetry of greater than 15 dB. Inferior cochlear vein involvement was identified in 19 of the 20 (95%) subjects with sensorineural hearing loss. Inferior cochlear vein involvement was found to be a statistically significant predictor of sensorineural hearing loss using univariate and multivariate analyses. Other imaging findings that were statistically significant predictors of sensorineural hearing loss include Glasscock-Jackson stage, Fisch-Mattox stage, hypoglossal canal involvement, jugulo-carotid spin erosion, and petrous carotid canal erosion. CONCLUSIONS: Involvement of the inferior cochlear vein appears to be a plausible mechanism for sensorineural hearing loss in patients with jugular foramen paraganglioma. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:67-75, 2019.

Association of Sudden Sensorineural Hearing Loss With Risk of Cardiocerebrovascular Disease: A Study Using Data From the Korea National Health Insurance Service.

Importance: The interruption of vascular supply to the cochlea has been proposed as a major etiological factor for sudden sensorineural hearing loss (SSNHL), and several risk factors for cardiocerebrovascular disease (CCVD) are associated with SSNHL, including heavy smoking, alcohol consumption, and thromboembolic events. However, the link between SSNHL and CCVD has not been fully evaluated. Objective: To investigate the association between SSNHL and CCVD. Design, Setting, and Participants: A retrospective propensity score-matched cohort study was conducted using a nationwide representative sample from the National Sample Cohort 2002 through 2013 data from the Korea National Health Insurance Service. The SSNHL group (n = 154) included certain patients who were diagnosed with SSNHL between January 2003 and December 2005. The comparison group was selected (4 patients for every 1 patient with SSNHL; n = 616) using propensity score matching, according to sociodemographic factors and the year of enrollment. Each patient was monitored until 2013. Main Outcomes and Measures: Survival analysis, the log-rank test, and Cox proportional hazards regression models were used to calculate the incidence, survival rate, and hazard ratio of CCVD for each group. Results: Among the 770 patients, 385 (50.0%) were female and 370 (48.1%) were aged between 45 and 64 years. Of the total study population, 66 patients developed CCVD, such as stroke and acute myocardial infarction, during the 11-year follow-up period: 18 patients in the SSNHL group (incidence, 13.5 cases per 1000 person-years) and 48 from the comparison group (incidence, 7.5 cases per 1000 person-years). After adjustment for other factors, the hazard ratio of CCVD during the 11-year follow-up period was 2.18 times (95% CI, 1.20-3.96) greater for patients with SSNHL. An increased risk of stroke was associated with SSNHL (HR, 2.02; 95% CI, 1.16-3.51); however, there was no relation between SSNHL and risk of myocardial infarction (HR, 1.18; 95% CI, 0.25-5.50). Conclusions and Relevance: This observational study using nationwide data suggests that SSNHL is associated with an increased incidence of CCVD, specifically stroke. Therefore, patient surveillance for signs of CCVD should be considered for patients who receive a diagnosis of SSNHL.

Non-invasive intraoperative monitoring of cochlear function by cochlear microphonics during cerebellopontine-angle surgery.

In vestibular-schwannoma (VS) surgery, hearing-preservation rate remains low. Besides damage to the cochlear nerve, intraoperative cochlear ischemia is a potential cause of hearing loss. Here, we used non-invasive cochlear microphonic (CM) recordings to detect the cochlear vascular events of VS surgery. Continuous intraoperative CM monitoring, in response to 80-95 dB SPL, 1-kHz tone-bursts, was performed in two samples of patients undergoing retrosigmoid cerebellopontine-angle surgery: one for VS (n = 31) and one for vestibular neurectomy or vasculo-neural conflict causing intractable trigeminal neuralgia, harmless to hearing (n = 19, control group). Preoperative and postoperative hearings were compared as a function of intraoperative CM changes and their chronology. Monitoring was possible throughout except for a few tens of seconds when drilling or suction noises occurred. Four patterns of CM time course were identified, eventless, fluctuating, abrupt or progressive decrease. Only the VS group displayed the last two patterns, mainly during internal-auditory-canal drilling and the ensuing tumor dissection, always with postoperative loss of hearing as an end result. Conversely, eventless and fluctuating CM patterns could be associated with postoperative hearing loss when the cochlear nerve had been reportedly damaged, an event that CM is not meant to detect. Cochlear ischemia is a frequent event in VS surgery that leads to deafness. The findings that CM decrease raised no false alarm, and that CM fluctuations, insignificant in control cases, were easily spotted, suggest that CM intraoperative monitoring is a sensitive tool that could profitably guide VS surgery.

Cochlear Pericytes Are Capable of Reversibly Decreasing Capillary Diameter In Vivo After Tumor Necrosis Factor Exposure.

OBJECTIVE: The aim of this work was to evaluate the effect of tumor necrosis factor (TNF) and its neutralization with etanercept on the capability of cochlear pericytes to alter capillary diameter in the stria vascularis. METHODS: Twelve Dunkin-Hartley guinea pigs were randomly assigned to one of three groups. Each group was treated either with placebo and then placebo, TNF and then placebo, or TNF and then etanercept. Cochlear pericytes were visualized using diaminofluorescein-2-diacetate and intravasal blood flow by fluorescein-dextrane. Vessel diameter at sites of pericyte somas and downstream controls were quantified by specialized software. Values were obtained before treatment, after first treatment with tumor necrosis factor or placebo and after second treatment with etanercept or placebo. RESULTS: Overall, 199 pericytes in 12 animals were visualized. After initial treatment with TNF, a significant decrease in vessel diameter at sites of pericyte somas (3.6 ±4.3%, n = 141) compared with placebo and downstream controls was observed. After initial treatment with TNF, the application of etanercept caused a significant increase (3.3 ±5.5%, n = 59) in vessel diameter at the sites of pericyte somata compared with placebo and downstream controls. CONCLUSION: We have been able to show that cochlear pericytes are capable of reducing capillary diameter after exposition to TNF. Moreover, the reduction in capillary diameter observed after the application of TNF is revertible after neutralization of tumor necrosis factor by the application of etanercept. It seems that contraction of cochlear pericytes contributes to the regulation of cochlear blood flow.

Fingolimod (FTY-720) is Capable of Reversing Tumor Necrosis Factor Induced Decreases in Cochlear Blood Flow.

HYPOTHESIS: The potential of Fingolimod (FTY-720), a sphingosine-1-phosphate analogue, to revoke the changes in cochlear blood flow induced by tumor necrosis factor (TNF) was investigated. BACKGROUND: Impairment of cochlear blood flow has often been considered as the common final pathway of various inner ear pathologies. TNF, an ubiquitous cytokine, plays a major role in these pathologies, reducing cochlear blood flow via sphingosine-1-phosphate-signaling. METHODS: Fifteen Dunkin-Hartley guinea pigs were randomly assigned to one of three groups (placebo/placebo, TNF/placebo, TNF/FTY-720). Cochlear microcirculation was quantified over 60 minutes by in vivo fluorescence microscopy before and after topical application of placebo or TNF (5 ng/ml) and after subsequent application of placebo or FTY-720 (200 µg/ml). RESULTS: Treatment with TNF led to a significant decrease of cochlear blood flow.Following this, application of placebo caused no significant changes while application of FTY-720 caused a significant rise in cochlear blood flow. CONCLUSIONS: FTY-720 is capable of reversing changes in cochlear blood flow induced by application of TNF. This makes FTY-720 a valid candidate for potential treatment of numerous inner ear pathologies.

[Tinnitus caused by heart disease and healed from heart].

Tinnitus is recognized as a refractory disease, which is common in clinic, and always treated from the liver and kidney. We treat tinnitus mainly by heart based on syndrome differentiation. It often works well when the left cukou pulse is abnormal. Referring to ancient literature, we find that the heart is related to ears by meridians, and the kidney and heart govern ears. The normal function of heart and kidney means normal hearing. The heart secretes atrial natriuretic polypeptins (ANP), whose receptor is widely distributed in ears and can increase the cochlear blood flow. In this paper we explore the relationship between the heart and the ears so as to provide theories of treatment by heart for tinnitus.

Aberrant Internal Carotid Artery in the Tympanic Cavity.

OBJECTIVES: Presence of aberrant internal carotid artery (ICA) in the tympanic cavity is a very rare case and therefore the diagnosis is a challenge. Here, the authors aimed to address the importance of the diagnosis since the intervention to the middle ear and implants is increasing in number and this condition may lead to life-threatening bleeding. METHODS: Between 2012 and 2016, among the patients referred to the authors' Radiology Department from the Department of Otolaringology for the evaluation of the temporal region for various indications, the authors reported this anomaly in 6 patients and multidetector computerized tomography of these 6 patients and magnetic resonance imaging of 2 were assessed in detail. RESULTS: The mean age of the 6 patients was 28.8 and aberrant ICA abnormality was observed in 2 patients bilaterally and 4 patients unilaterally on the right side. In 1 patient ICA was not totally regressed and observed as hypoplastic. In one of the patients, dehiscence was evident between ICA and the cochlea. Moreover, in 1 patient the contralateral ICA was not observed. CONCLUSION: Although rare, aberrant ICA is an abnormality that should be kept in mind by the clinicians and the radiologists, since it leads to abundant bleeding when undiagnosed before the surgical interventions.

The effect of propofol infusion with topical epinephrine on cochlear blood flow and hearing: An experimental study.

BACKGROUND AND OBJECTIVE: Propofol is the most commonly used intravenous (IV) anesthetic agent and is associated with hypotension upon induction of anesthesia. Intravenous propofol infusion has several properties that may be beneficial to patients undergoing middle ear surgery. Topical application of concentrated epinephrine is a valuable tool for achieving hemostasis in the middle ear and during mastoid surgery. The purpose of the present study was to determine the effects of propofol infusion with topical epinephrine on cochlear blood flow (CBF) and hearing in rats. MATERIALS AND METHODS: Twenty one male Sprague-Dawley rats were divided into three groups. The rate of intravenous infusion of propofol was 4-6 ml/kg/hour. The first group (control group, n = 7) was given IV infusion of phosphate buffered saline (PBS) with topical application of PBS in the round window. In study group A (n = 7), the effect of topical phosphate buffered saline with IV infusion of propofol on CBF and hearing was evaluated. In study group B (n = 7), additional effects of topical epinephrine with IV infusion of propofol on CBF and hearing were evaluated. The laser Doppler blood flowmeter, CBF, and the mean arterial blood pressure (MAP) were measured and analyzed. Additionally, hearing test using auditory brainstem response (ABR) was performed in both groups. RESULTS: In both groups, infusion of propofol induced a time-dependent decrease in MAP. Approximately 30 min after the start of the propofol infusion, the CBF started to decrease slowly. The decrease in CBF was significantly greater in the study group compared to the control group. The threshold was elevated in the study group relative to the control group. CONCLUSION: During middle ear surgery, use of IV infusion of propofol with topical epinephrine cotton ball or cottonoid application is not recommended.

Tumor Necrosis Factor-induced Decrease of Cochlear Blood Flow Can Be Reversed by Etanercept or JTE-013.

HYPOTHESIS: This study aimed to quantify the effects of tumor necrosis factor (TNF) inhibitor Etanercept and sphingosine-1-phosphate receptor 2 antagonist JTE-013 on cochlear blood flow in guinea pigs after TNF-induced decrease. BACKGROUND: Sudden sensorineural hearing loss is a common cause for disability and reduced quality of life. Good understanding of the pathophysiology and strong evidence-based therapy concepts are still missing. In various inner ear disorders, inflammation and impairment of cochlear blood flow (CBF) have been considered factors in the pathophysiology. A central mediator of inflammation and microcirculation in the cochlea is TNF. S1P acts downstream in one TNF pathway. METHODS: Cochlea lateral wall vessels were exposed surgically and assessed by intravital microscopy in guinea pigs in vivo. Twenty-eight animals were randomly distributed into four groups of seven each. Exposed vessels were superfused by TNF (5.0 ng/ml) and afterward repeatedly either by Etanercept (1.0 µg/ml), JTE-013 (10 µmol/L), or vehicle (0.9 % NaCl solution or ethanol: phosphate-buffered saline buffer, respectively). RESULTS: After decreasing CBF with TNF (p <0.001, two-way RM ANOVA), both treatments reversed CBF, compared with vehicle (p <0.001, two-way RM ANOVA). The comparison of the vehicle groups showed no difference (p = 0.969, two-way RM ANOVA), while there was also no difference between the treatment groups (p = 0.850, two-way RM ANOVA). CONCLUSION: Both Etanercept and JTE-013 reverse the decreasing effect of TNF on cochlear blood flow and, therefore, TNF and the S1P-signalling pathway might be targets for treatment of microcirculation-related hearing loss.