Neuronal Cytoglobin in the Auditory Brainstem of Rat and Mouse: Distribution, Cochlear Projection, and Nitric Oxide Production.

Cytoglobin (Cygb), a hemoprotein of the globin family, is expressed in the supportive tissue cells of the fibroblast lineage and in distinct neuronal cell populations. The expression pattern and regulatory parameters of fibroblasts and related cells were studied in organs such as the kidney and liver in a variety of animal models. In contrast, knowledge about cytoglobin-expressing neurons is sparse. Only a few papers described the distribution in the brain as ubiquitous with a restricted number of neurons in focal regions. Although there is evidence for cytoglobin involvement in neuronal hypoxia tolerance, its presence in the auditory system was not studied despite high metabolism rates and oxygen demands of the cochlea and related brainstem centers. In a continuation of a previous study demonstrating Cygb-neurons in, inter alia, auditory regions of the mouse brain, we concentrated on the superior olivary complex (SOC) in the present study. We sought to investigate the distribution, projection pattern and neurochemistry of Cygb-neurons in the SOC. We conducted immunohistochemistry using a Cygb antibody and found that this brainstem region, functionally competent for bilateral hearing and providing cochlear hair cell innervation, contains a considerable number of Cygb-expressing neurons (averaging 2067 ± 211 making up 10 ±1% percent of total neuron number) in rats, and 514 ± 138 (6 ± 1%) in mice. They were observed in all regions of the SOC. Retrograde neuronal tract tracing with Fluorogold injected into the cochlea demonstrated that 1243 ± 100 (6 ± 1% of total neuron number in rat SOC)) were olivocochlear neurons. Approximately 56% of total Cygb neurons were retrogradely labelled, while the majority of olivocochlear neurons of both lateral and medial systems were Cygb-immunoreactive. We also conducted double immunofluorescence staining for Cygb and neuronal nitric oxide synthase (nNOS), the enzyme responsible for nitric oxide production, and observed that cytoglobin in the SOC frequently co-localized with nNOS. Our findings suggest that cytoglobin plays an important physiologic role in the oxygen homeostasis of the peripheral and central auditory nervous system. Further studies, also including transgenic animal models, are required to shed more light on the function(s) of Cygb in neurons, in particular of the auditory system.

Leiomyosarcoma of the Nasal Cavity.

Leiomyosarcoma (LMS) in the sinonasal tract (SNT) is a rarity that has been firstly described in 1958. Since then, there have been only a few articles about this entity. Most of the data available about LMS in the SNT is derived from case reports. We believe that our case will support the data set and help guiding the management of this rare condition. A 84-year-old female presented with nasal airway obstruction on the left side. She experienced several episodes of epistaxis from her left nostril, what made her to seek medical care. A rhinoscopy revealed an obstructing mass in the left nasal cavity. Computed tomography (CT) scan of the paranasal sinuses revealed a homogenous mass occupying the left nasal cavity, bone destruction of the left middle, and inferior nasal turbinates. An infiltration of the left nasolacrimal duct was also present. The patient refused to undergo open surgery and the mass was removed during an endoscopic approach. The histopathological analysis combined with immunohistochemistry was consistent with LMS. The resection margins were positive for tumor cells. A staging with CT-neck-thorax, abdomen ultrasound, and MRI of the head ruled out metastases. She underwent a second endoscopic tumor resection surgery with positive resection margins and obtained adjuvant radiotherapy. On 9 months of follow-up, there was no recurrence or metastases.

Not All Embolizations Are Created Equally in the Management of Posterior Epistaxis: Discussion of Safety Measures Avoiding Neurological Complications.

Today, there are still no uniform guidelines for the treatment of epistaxis. Furthermore, it is widely debated whether embolization or surgical approaches should be the first choice of treatment for intractable posterior epistaxis after conservative measures have failed. In several meta-analyses, it is reported that endoscopic sphenopalatine artery ligation and embolization have similar success rates, but embolization was associated with more severe neurological complications. Regarding existing literature, there are many comparative analyses of surgical methods but none for embolization protocols. Against this backdrop of a lack of uniform standards in embolization techniques, we present a retrospective evaluation of what has emerged to be best procedural practice for endovascular treatment of epistaxis in our department using microsphere particles and microcoils, in particular regarding precaution measures to avoid neurological complications. In our retrospective data analysis of 141 procedures in 123 patients, performed between 2008 and 2019, we find success rates very similar to those reported in other studies (95.1% immediate-stop-of-bleeding success and 90.2% overall embolization success) but did not encounter any major neurological complication opposed to other reports. We suggest some aspects of our protocol as precaution measure to avoid neurological complications. More generally and perhaps even more importantly, we make a strong case for standardization for embolization techniques to the level of details in surgical procedure standardization to enable an apples to apples comparison of embolization techniques to each other and of intervention vs. surgery.

Long-Term Quality of Life and Nutritional Status of Patients with Head and Neck Cancer.

Disease and therapy of head and neck cancer impair quality of life (QOL). QOL varies profoundly during therapy and follow-up. AIM: We sought to monitor QOL and nutritional status of patients before, during and after therapy (AT). PATIENTS AND METHODS: This study evaluates QOL by using the EORTC-questionnaires QLQ-C30 and H&N35, body weight and plasma albumin up to two years AT. RESULTS: Chemoradiotherapy is the period of the most profound QOL-impairment. Postoperative QOL almost reaches preoperative levels just before adjuvant therapy and does not differ significantly from pretherapeutic QOL. Long-term QOL is not significantly deteriorated. Patients have an average weight loss of 17%. Nutritional supplements are used continuously. Xerostomia and sticky saliva are chronic symptoms that persist AT. CONCLUSIONS: QOL is an important parameter for the evaluation of therapy success. Head and neck cancer and its therapy cause permanent xerostomia, sticky saliva and need of nutritional supplements. Adequate patient information, psychooncological counseling, analgesia and nutritional support may alleviate QOL impairment.

Neuroglobin Expression in the Mammalian Auditory System.

The energy-yielding pathways that provide the large amounts of metabolic energy required by inner ear sensorineural cells are poorly understood. Neuroglobin (Ngb) is a neuron-specific hemoprotein of the globin family, which is suggested to be involved in oxidative energy metabolism. Here, we present quantitative real-time reverse transcription PCR, in situ hybridization, immunohistochemical, and Western blot evidence that neuroglobin is highly expressed in the mouse and rat cochlea. For primary cochlea neurons, Ngb expression is limited to the subpopulation of type I spiral ganglion cells, those which innervate inner hair cells, while the subpopulation of type II spiral ganglion cells which innervate the outer hair cells do not express Ngb. We further investigated Ngb distribution in rat, mouse, and human auditory brainstem centers, and found that the cochlear nuclei and superior olivary complex (SOC) also express considerable amounts of Ngb. Notably, the majority of olivocochlear neurons, those which provide efferent innervation of outer hair cells as identified by neuronal tract tracing, were Ngb-immunoreactive. We also observed that neuroglobin in the SOC frequently co-localized with neuronal nitric oxide synthase, the enzyme responsible for nitric oxide production. Our findings suggest that neuroglobin is well positioned to play an important physiologic role in the oxygen homeostasis of the peripheral and central auditory nervous system, and provides the first evidence that Ngb signal differentiates the central projections of the inner and outer hair cells.

Absence of Early Neuronal Death in the Olivocochlear System Following Acoustic Overstimulation.

This study was conducted to examine possible effects of noise trauma on olivocochlear (OC) neurons. Anesthetized rats were exposed to a continuous 10 kHz pure tone at 120 dB sound pressure level for 2 hrs. The effects of treatment were verified by recordings of auditory brainstem response and distortion product otoacoustic emission. Three or 8 days after acoustic trauma, rats received unilateral injections of an aqueous solution of the retrograde neuronal tracer Fluorogold (FG) into the scala tympani to identify OC neurons (OCN). Five days after FG injection, brains were perfusion-fixed, and brainstem sections were cut and analyzed with respect to FG-labeled neurons. We found that, in both groups, numbers of OCN were similar to that of controls. The incubation of a second set of sections with antibodies against choline-acetyltransferase (the enzyme responsible for acetylcholine synthesis) showed the cholinergic neurons of the brainstem, however, without suggesting differences between groups. Our study, the first to investigate noise trauma effects on identified OCN, revealed that no visible alterations occurred in 2 weeks following trauma, neither in identified OCN nor in choline-acetyltransferase-immunofluorescence. At this time, auditory brainstem response and distortion product otoacoustic emission measurements showed severe signs of hearing loss. The mechanisms leading to hearing loss upon noise trauma apparently do not involve degeneration of OCN.

The rhinolith-a possible differential diagnosis of a unilateral nasal obstruction.

Rhinoliths are mineralised foreign bodies in the nasal cavity that are a chance finding at anterior rhinoscopy. Undiscovered, they grow appreciably in size and can cause a foul-smelling nasal discharge and breathing problems. Giant nasal stones are now a very rare occurrence, since improved diagnostic techniques, such as endoscopic/microscopic rhinoscopy, now make it possible to identify foreign bodies at an early stage of development. We report the case of a 37-year-old patient who, at the age of 5-6 years, introduced a foreign body, probably a stone, into his right nasal cavity. On presentation, he complained of difficulty in breathing through the right nostril that had persisted for the last 10 years. For the past four years a strong fetid smell from the nose had been apparent to those in his vicinity. Under general anaesthesia, the stone was removed in toto from the right nasal cavity. The possible genesis of the rhinolith is discussed, our case compared with those described in the literature, and possible differential diagnoses are considered.

The influence of nocturnal alcohol ingestion on snoring.

Nocturnal alcohol ingestion is known to increase obstructive sleep apnea. It is assumed that snoring also increases under the influence of alcohol although only few data are available to support this hypothesis. The aim of this study was to investigate the influence of nocturnal alcohol ingestion on the properties of snoring. Twenty healthy male reported non-snorers (n = 10) and snorers (n = 10) underwent night-time polysomnography at three randomly assigned nights with a blood alcohol concentration (BAC) of 0.0, 0.5 and 0.8 per thousand, respectively. Snoring events were recorded by a room and body contact microphone simultaneously. Loudness and incidence of snoring were calculated and correlated to the total sleep time (TST), body position and sleep stages. Snorers revealed an increase of the apnea-hypopnea-index (AHI) under increasing BAC, whereas no decrease in the nocturnal SAO(2) was detected. Non-snorers had no increase in the AHI but a decrease in SAO(2). Snoring individuals revealed a dose-dependent increase of incidence (TSI) and loudness (LSI) of snoring with regard to the TST. The TSI increased by a factor of 1.6 at 0.5 per thousand BAC and by 4.2 at 0.8 per thousand BAC compared to the 0.0 per thousand- BAC-night. The LSI increased threefold at 0.5 per thousand BAC and 14-fold at 0.8 per thousand BAC. Snoring increased to a bigger extent in a supine position compared to non supine and during REM stage as well as Non REM 3/4 stage. Non-snorers did not present any effect of alcohol on the snoring properties with regard to TST, body position and sleep stage. The results indicate that nocturnal alcohol ingestion affects individuals with a reported history of snoring to a greater extent than non-snorers. Non-snorers did not turn into snorers under increasing alcohol influence. The recommendation, to avoid alcohol intake prior to sleep, gains of special clinical importance for individuals already snoring.

Neurochemistry of olivocochlear neurons in the hamster.

The present study was conducted to characterize the superior olivary complex (SOC) of the lower brain stem in the pigmented Djungarian hamster Phodopus sungorus. Using Nissl-stained serial cryostat sections from fresh-frozen brains, we determined the borders of the SOC nuclei. We also identified olivocochlear (OC) neurons by retrograde neuronal tracing upon injection of Fluoro-Gold into the scala tympani. To evaluate the SOC as a putative source of neuronal nitric oxide synthase (nNOS), arginine-vasopressin (AVP), oxytocin (OT), vasoactive intestinal polypeptide (VIP), or pituitary adenylate cyclase-activating polypeptide (PACAP) that were all found in the cochlea, we conducted immunohistochemistry on sections exhibiting retrogradely labeled neurons. We did not observe AVP-, OT-, or VIP-immunoreactivity, neither in OC neurons nor in the SOC at all, revealing that cochlear AVP, OT, and VIP are of nonolivary origin. However, we found nNOS, the enzyme responsible for nitric oxide synthesis in neurons, and PACAP in neuronal perikarya of the SOC. Retrogradely labeled neurons of the lateral olivocochlear (LOC) system in the lateral superior olive did not contain PACAP and were only infrequently nNOS-immunoreactive. In contrast, some shell neurons and some of the medial OC (MOC) system exhibited immunofluorescence for either substance. Our data obtained from the dwarf hamster Phodopus sungorus confirm previous observations that a part of the LOC system is nitrergic. They further demonstrate that the medial olivocochlear system is partly nitrergic and use PACAP as neurotransmitter or modulator.

Neurochemistry of identified motoneurons of the tensor tympani muscle in rat middle ear.

The objective of the present study was to identify efferent and afferent transmitters of motoneurons of the tensor tympani muscle (MoTTM) to gain more insight into the neuronal regulation of the muscle. To identify MoTTM, we injected the fluorescent neuronal tracer Fluoro-Gold (FG) into the muscle after preparation of the middle ear in adult rats. Upon terminal uptake and retrograde neuronal transport, we observed FG in neurons located lateral and ventrolateral to the motor trigeminal nucleus ipsilateral to the injection site. Immunohistochemical studies of these motoneurons showed that apparently all contained choline acetyltransferase, demonstrating their motoneuronal character. Different portions of these cell bodies were immunoreactive to bombesin (33%), cholecystokinin (37%), endorphin (100%), leu-enkephalin (25%) or neuronal nitric oxide synthase (32%). MoTTM containing calcitonin gene-related peptide, tyrosine hydroxylase, substance P, neuropeptide Y or serotonin were not found. While calcitonin gene-related peptide was not detected in the region under study, nerve fibers immunoreactive to tyrosine hydroxylase, substance P, neuropeptide Y or serotonin were observed in close spatial relationship to MoTTM, suggesting that these neurons are under aminergic and neuropeptidergic influence. Our results demonstrating the neurochemistry of motoneuron input and output of the rat tensor tympany muscle may prove useful also for the general understanding of motoneuron function and regulation.

Motoneurons of the stapedius muscle in the guinea pig middle ear: afferent and efferent transmitters.

The objective of the present study was to identify efferent and afferent transmitters of motoneurons of the stapedius muscle of the middle ear in order to gain more insight into the neuronal regulation of the muscle. To identify motoneurons, we injected the fluorescent neuronal tracer Fluorogold (FG) into the muscle after preparation of the middle ear in adult guinea pigs. Upon terminal uptake and retrograde neuronal transport, we observed FG in neurons located medial and ventral to the nucleus of the facial nerve ipsilateral to the injection site. Immunohistochemical studies of these motoneurons showed that the majority contains calcitonin gene-related peptide. Our data further demonstrate close spatial relationships of motoneurons to structures immunoreactive to either serotonin, substance P or neuronal nitric oxide and reveal that these neurons are under neuropeptidergic and nitrergic influence.

Alcohol ingestion influences the nocturnal cardio-respiratory activity in snoring and non-snoring males.

Night time alcohol ingestion influences nocturnal breathing in patients with sleep apnea syndrome or respiratory diseases. To evaluate the influence of nocturnal alcohol ingestion on the cardio-respiratory activity of healthy men, 8 snoring and 13 non-snoring male subjects were measured for 3 nights after alcohol ingestion. Blood alcohol concentration was 0.0, 0.5 and 0.8%, respectively. During each night polysomnographic data were obtained and analyzed. The apnea-hypopnea index was significantly higher in snoring than in non-snoring participants and increased in both groups under the influence of alcohol. Non-snoring males showed a significant increase of hypopneas under nocturnal alcohol ingestion (0.96-1.65-2.06). Mean oxygen saturation (SAO(2)) was significantly higher in non-snoring compared to snoring males, and both groups showed a significant decrease (non-snoring: 96.06%-95.7%-95.52%; snoring: 95.54%-94.74%-94.53%). Snoring individuals had a significant decrease in SAO(2) during NREM4, whereas SAO(2) was reduced significantly in REM and NREM3 in non-snoring subjects. The nocturnal heart rate was significantly increased in both groups under the influence of alcohol. The study proves that snoring and non-snoring healthy males are affected by nocturnal alcohol ingestion. Under the effect of alcohol, these patients can develop signs of a sleep apnea syndrome, which should be considered clinically.

A nitrergic projection from the superior olivary complex to the inferior colliculus of the rat.

The present study was conducted to test whether the ascending auditory projection from the superior olivary complex (SOC) of the brainstem to the inferior colliculus (IC) may use nitric oxide (NO) as a neuroactive compound. We identified olivo-collicular projection neurons in subnuclei of the SOC by retrograde neuronal tracing with Fluoro-Gold (FG) injected into the central nucleus of the IC. Sections containing retrograde labelled neurons were subjected to immunohistochemical incubation in an antiserum directed against the enzyme responsible for NO production in nerve cells, neuronal NO synthase (nNOS). The analysis showed that FG-containing neurons as well as nNOS-immunoreactive neurons were present in the lateral superior olive (LSO), superior paraolivary nucleus (SPO), ventral nucleus of the trapezoid body (VNTB), medial superior olive (MSO) and in dorsal and ventral periolivary regions to different amounts. However, only in the LSO, SPO and VNTB double-labelled neurons were found. They made up to less than 10% of all nNOS neurons in the SOC. Considering that only about 5% of the nNOS cells in the SOC are olivocochlear neurons [Riemann and Reuss, 1999], it is still open whether the majority of nitrergic neurons of the SOC project to other sites or whether they rather have intrinsic actions in providing NO to the SOC.