Intact Nerve Research Articles

Electrical stimulation of the dorsal motor nucleus of the vagus in male mice can regulate inflammation without affecting the heart rate

BackgroundThe vagus nerve plays an important role in neuroimmune interactions and in the regulation of inflammation. A major source of efferent vagus nerve fibers that contribute to the regulation of inflammation is the brainstem dorsal motor nucleus of the vagus (DMN), as recently shown using optogenetics. In contrast to optogenetics, electrical neuromodulation has broad therapeutic implications. However, the anti-inflammatory effectiveness of electrical stimulation of the DMN (eDMNS) and the possible heart rate (HR) alterations associated with this approach have not been investigated. Here, we examined the effects of eDMNS on HR and cytokine levels in mice administered with lipopolysaccharide (LPS, endotoxin) and in mice subjected to cecal ligation and puncture (CLP) sepsis. MethodsAnesthetized male 8–10-week-old C57BL/6 mice on a stereotaxic frame were subjected to eDMNS using a concentric bipolar electrode inserted into the left or right DMN or sham stimulation. eDMNS (500, 250 or 50 μA at 30 Hz, for 1 min) was performed and HR recorded. In endotoxemia experiments, sham or eDMNS utilizing 250 μA or 50 μA was performed for 5 mins and was followed by LPS (0.5 mg/kg) i.p. administration. eDMNS was also applied in mice with cervical unilateral vagotomy or sham operation. In CLP experiments sham or left eDMNS was performed immediately post CLP. Cytokines and corticosterone were analyzed 90 mins after LPS administration or 24 h after CLP. CLP survival was monitored for 14 days. ResultsEither left or right eDMNS at 500 μA and 250 μA decreased HR, compared with baseline pre-stimulation. This effect was not observed at 50 μA. Left side eDMNS at 50 μA, compared with sham stimulation, significantly decreased serum and splenic levels of the pro-inflammatory cytokine TNF and increased serum levels of the anti-inflammatory cytokine IL-10 during endotoxemia. The anti-inflammatory effect of eDMNS was abrogated in mice with unilateral vagotomy and was not associated with serum corticosterone alterations. Right side eDMNS in endotoxemic mice suppressed serum TNF and increased serum IL-10 levels but had no effects on splenic cytokines. In mice with CLP, left side eDMNS suppressed serum IL-6, as well as splenic IL-6 and increased splenic IL-10 and significantly improved the survival rate of CLP mice. ConclusionsFor the first time we show that a regimen of eDMNS which does not cause bradycardia alleviates LPS-induced inflammation. These eDMNS anti-inflammatory effects require an intact vagus nerve and are not associated with corticosteroid alterations. eDMNS also decreases inflammation and improves survival in a model of polymicrobial sepsis. These findings are of interest for further studies exploring bioelectronic anti-inflammatory approaches targeting the brainstem DMN.

Open Exploration and Reduction of Paediatric Supracondylar Humerus Fracture with Pink, Pulseless Hand in Resource-Limited Settings.

Background: Supracondylar humerus fractures (SHFs) are common paediatric injuries, with high risk of vascular compromise. Some patients present with a 'pink, pulseless hand', caused by occlusion of brachial artery flow but with collateral circulation preserving distal perfusion. Management of these patients remains controversial, especially when resources may be limited for prolonged hospitalisation and serial monitoring by skilled staff. The aim of this study is to present the intraoperative findings, surgical procedures done and outcomes at 6 weeks for patients with paediatric supracondylar fractures with a pink pulseless hand. Methods: We retrospectively identified 13 patients who presented to a public hospital between January 2019 and May 2023 with a displaced SHF and pink, pulseless hand. All patients underwent an open reduction with an anterior approach allowing for exploration, protection and repair of neurovascular structures. Distal flow was restored in the brachial artery either with topical lidocaine application, thrombectomy or artery reconstruction. Results: Out of 13 patients, all had intact median nerves and 10 had intact arteries (69%), of which seven were interposed at the fracture site and four were in vasospasm. Of the three patients with true arterial injury (23%), two had a crushed artery and one had thrombosis of the artery. Peripheral pulses were restored within an hour of fracture open reduction in all patients. At final follow-up, a mean 6 weeks postoperatively, all patients had recovered without neurovascular deficit, compartment syndrome or Volkmann ischemic contracture. Conclusions: In resource-limited settings, we recommend performing open exploration and reduction for patients with SHFs with pink, pulseless hand. This approach prevents iatrogenic neurovascular injury during closed reduction attempts, allows for immediate repair of a brachial artery injury and avoids unnecessary hospitalisation and serial monitoring. Level of Evidence: Level IV (Therapeutic).

(059) Effects of a Red-Light–Controllable Nitric Oxide Donor, NORD-1, on Diabetes Mellitus-Induced Erectile Dysfunction in Rats

Abstract Introduction Diabetes mellitus (DM) often causes erectile dysfunction (ED). Phosphodiesterase-5 inhibitor has limited effects on diabetes mellitus-induced erectile dysfunction (DMED). One contributing factor to this reduced effect is the decreased production of nitric oxide owing to neuropathy and endothelial impairment. To address this issue, we developed a red-light–controllable nitric oxide donor, NORD-1, that successfully enhanced erectile function in intact and cavernous nerve injury model rats. Objective In this study, we investigated whether NORD-1 and red-light irradiation could improve DMED in rats. Methods Seven-week-old Sprague–Dawley male rats were used. Rats in the DM and sham groups were intravenously administered streptozotocin 50 mg/kg and saline, respectively. One week after treatment, the blood glucose levels of rats in the DM group were found to be over 250 mg/dL. Five weeks after the treatment, we performed a functional study using the measurements of intracavernous pressure (ICP) under the stimulation of the cavernous nerve. The study was performed before and after NORD-1 treatment, both with and without light irradiation. Additionally, we performed an isometric tension study using corpus cavernosum from rats treated with either NORD-1 or a control compound, SiR650. Results The ICP/MAP ratio of the DM group was significantly lower than that of the sham group before and after NORD-1 treatment without light irradiation (both P<0.05). However, after NORD-1 treatment with light irradiation, the ICP/MAP ratios of the Sham and DM groups were substantially enhanced compared with that before and after NORD-1 treatment without light irradiation (all P<0.05). The ICP/MAP ratio of the DM group was similar to that of the Sham group under the normal condition before NORD-1 treatment by light irradiation. Moreover, systemic blood pressure was not affected by NORD-1 and light irradiation. In the isometric tension study, rat corpus cavernosum from rats treated with SiR650 showed no changes under red light in both the Sham and DM groups. However, the corpus cavernosum from rats treated with NORD-1 was strongly relaxed by red light in both groups. Conclusions NORD-1 and red-light irradiation could improve DMED in STZ-induced DM rats without lowering blood pressure. Disclosure No.

Validation of the Root Analysis Score for C5 Viability in Patients With Pan–Brachial Plexus Injury

Pan-brachial plexus injury patients present a reconstructive challenge. The root analysis score, developed from parsimonious multivariable modeling of 311 pan-brachial plexus injury patients, determines the probability of having a viable C5 nerve based on four categories: positive C5 Tinel test, intact C5 nerve on computed tomography myelogram, lack of hemidiaphragmatic elevation, and absence of midcervical paraspinal fibrillations. Root analysis scores were calculated for a separate cohort of patients with pan-brachial plexus injuries. Scores were validated by the presence or absence of a graftable C5 root, based on supraclavicular exploration and intraoperative electrophysiologic testing. Receiver operating characteristic curve, accuracy, and concordance statistic of the scores were calculated. Patients were divided into three root analysis score cohorts: less than 50 (low), 50-75 (average), and 75-100 points (high) based on dividing the score into quartiles and combining the lowest two. The probability, sensitivity, and specificity of each cohort having an available C5 nerve were based on the intraoperative assessment. Eighty patients (mean age, 33.1 years; 15 women and 65 men) were included. Thirty-one patients (39%) had a viable C5 nerve. The root analysis calculator had an overall accuracy of 82.5%, a receiver operating characteristic of 0.87, and a concordance statistic of 0.87, demonstrating high overall predictive value; 6.5% of patients with a score of less than 50 (94% sensitivity and 43% specificity), 16.1% of patients with a score of 50-75 (94% sensitivity and 67% specificity), and 77.4% of patients with a score of 75-100 (77% sensitivity and 90% specificity) had a graftable C5 nerve. The root analysis score demonstrated high accuracy and predictive power for a viable C5 nerve. In patients with a score of less than 50, the necessity of supraclavicular root exploration should balance patient factors, presentation timing, and concomitant injuries. Diagnosis II.

Radiation-Induced Sensorineural Hearing Loss and Potential Management

The cochlear apparatus is one of the major organs at risk when considering radiation therapy (RT) for brain, head, and neck tumors. Radiation oncologists currently consider mean dose constraints of <35 Gy for conventionally fractioned radiation therapy (RT), <4 Gy for single fraction stereotactic radiosurgery, and <17.1 or 25 Gy for 3- or 5-fraction stereotactic radiosurgery, respectively, as the standard of care. Indeed, dose adjustments are made in the setting of concurrent platinum-based chemotherapy or when prioritizing tumor coverage during treatment planning. Despite guidelines, in many patients, RT to the cochlea may still cause sensorineural hearing loss through progressive degeneration and ossification of the inner ear. There are several audiologic and otolaryngologic interventions for incident RT-induced hearing loss, including hearing aids, cochlear implants, or, in the context of vestibular schwannoma due to neurofibromatosis type 2, auditory brain stem implantation. Cochlear implants are the most effective at restoring hearing and improving quality of life for those with an intact cochlear nerve. An early multidisciplinary approach is essential to optimally manage RT-induced hearing loss, and this topic discussion serves as a guide for radiation oncologists on cochlear dosimetric considerations as well as how to address potential RT-induced adverse effects.

Brief Electrical Stimulation Promotes Recovery after Surgical Repair of Injured Peripheral Nerves.

Injured peripheral nerves regenerate their axons in contrast to those in the central nervous system. Yet, functional recovery after surgical repair is often disappointing. The basis for poor recovery is progressive deterioration with time and distance of the growth capacity of the neurons that lose their contact with targets (chronic axotomy) and the growth support of the chronically denervated Schwann cells (SC) in the distal nerve stumps. Nonetheless, chronically denervated atrophic muscle retains the capacity for reinnervation. Declining electrical activity of motoneurons accompanies the progressive fall in axotomized neuronal and denervated SC expression of regeneration-associated-genes and declining regenerative success. Reduced motoneuronal activity is due to the withdrawal of synaptic contacts from the soma. Exogenous neurotrophic factors that promote nerve regeneration can replace the endogenous factors whose expression declines with time. But the profuse axonal outgrowth they provoke and the difficulties in their delivery hinder their efficacy. Brief (1 h) low-frequency (20 Hz) electrical stimulation (ES) proximal to the injury site promotes the expression of endogenous growth factors and, in turn, dramatically accelerates axon outgrowth and target reinnervation. The latter ES effect has been demonstrated in both rats and humans. A conditioning ES of intact nerve days prior to nerve injury increases axonal outgrowth and regeneration rate. Thereby, this form of ES is amenable for nerve transfer surgeries and end-to-side neurorrhaphies. However, additional surgery for applying the required electrodes may be a hurdle. ES is applicable in all surgeries with excellent outcomes.

Clinical associations of corneal neuromas with ocular surface diseases.

Corneal neuromas, also termed microneuromas, refer to microscopic, irregularly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury. The formation of corneal neuromas results from damage to corneal nerves, such as following corneal pathology or corneal or intraocular surgeries. Initially, denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers, and later injured axons regenerate and new sprouts called neuromas develop. In recent years, analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy, a non-invasive imaging technique with microscopic resolution, has been used to evaluate corneal neuropathy and ocular surface dysfunction. Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes, and are a promising surrogate biomarker for ocular surface diseases, such as neuropathic corneal pain, dry eye disease, diabetic corneal neuropathy, neurotrophic keratopathy, Sjögren's syndrome, bullous keratopathy, post-refractive surgery, and others. In this review, we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas, as well as elaborated on their pathogenesis, visualization via in vivo confocal microscopy, and utility in monitoring treatment efficacy. As current quantitative analysis on neuromas mainly relies on manual annotation and quantification, which is user-dependent and labor-intensive, future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner, allowing it to be applied in clinical settings more efficiently. Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.

Differential Protein Expression between the Motor and Sensory Fascicles in Rat Femoral Nerve Injury.

It is important to distinguish between motor and sensory fascicles of the peripheral nerves for nerve alignment in surgery. However, there are no biomarkers currently available for effective identification of motor or sensory fascicles. The objective of this study was to identify differentially expressed proteins between motor and sensory fascicles of rats in response to injury. The study was carried out using a rat femoral nerve injury model. A proteomic analysis was performed to detect differential protein expression using samples of bilateral motor and sensory branches of intact and injured rat femoral nerves through fluorescent two-dimensional difference gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectrometry. Chi-square tests and t-tests were performed for comparison between motor or sensory nerve groups. The data identified six proteins that were differentially expressed between motor and sensory fascicles (>1.5-fold, P < 0.05), including apolipoprotein E, neurofilament light polypepticle, TEC kinase, serine protease inhibitor A3N, peroxiredoxin-2, and TPM1. The proteomic results were consistent with the mRNA expression levels of these genes as determined by quantitative reverse transcription polymerase chain reaction. Our study suggests that these proteins may play roles in nerve regeneration and repair. Importantly, apolipoprotein E and Serpina3n may serve as specific biomarkers for distinguishing motor and sensory fascicles of the peripheral nerves for nerve alignment in surgery.

Molecular and cellular changes underlying plasticity and regeneration of intact, injured and aged cold corneal nerves

The peripheral nerve endings from trigeminal neurons that innervate the cornea are key neural structures to detect and encode the features of the physical and chemical external stimuli at the ocular surface. These neurons are functionally diverse and have been classified into polymodal nociceptors, mechano‐nociceptors and cold thermoreceptors. Each functional type evokes qualitative different conscious sensations. The sensory modality that is generated from a nerve ending is determined by the type and specific characteristics of the ion channels involved in stimulus transduction and encoding. Among them, TRPM8 channels transduce both cold and osmotic stimuli in corneal cold nerve terminals. These cold thermoreceptors mediate sensations of ocular surface cooling and dryness, and play an important role in the regulation of basal tearing and blinking. Morphologically, cold thermosensitive neurons display a more complex branching of their peripheral nerve endings innervating the cornea in comparison to the other functional classes of sensory neurons.With aging, TRPM8‐expressing cold sensory neurons innervating the mouse cornea experience morphological and functional alterations. These changes occur earlier and are more prominent at the nerve terminal than at the neuron cell body. A drastic reduction of the nerve terminal branching complexity in addition to lower background impulse activity is observed in cold nerves of aged mice. Similarly, after performing photorefractive keratectomy (PRK) in the adult mouse cornea, both the nerve terminal branching and background activity are reduced in a fraction of the cold nerve terminals. An altered morphological configuration along with an aberrant transducing and coding ion channels expression at corneal cold nerve terminals are likely to contribute to the discomfort sensations experienced after corneal surgery and to the age‐related abnormal tearing in the elderly.(Supported by PID2021‐124460OB‐I00 from DOI: MCIN/AEI/ 10.13039/501100011033, and CIPROM/2021/48 from the Generalitat Valenciana, Spain)

Voice Changes Without Laryngeal Nerve Alterations After Thyroidectomy: The Need For Prospective Trials - A Review Study.

Thyroidectomy is a commonly performed surgical procedure that is offered for different thyroid pathologies. The most frequent complication after total thyroidectomy is transient or permanent hypoparathyroidism followed by transient or permanent recurrent laryngeal nerve palsy. Patients may experience voice impairment despite intact laryngeal nerve function. These patients are of special interest because they experience subjective symptoms which are difficult to measure and therefore to treat. The Voice Handicap Index (VHI) and VHI-10 are the most commonly used subjective questionnaires. Their results correlate with objective findings. Female sex, in particular after menopause, is a dominant factor for developing voice impairment after thyroidectomy. The extent of neck surgery and the weight and volume of the removed thyroid correlates directly with both objective and subjective voice impairment after surgery. Videolaryngostroboscopy should be considered to examine vocal cord pathologies in this patient group. Surprisingly, there are no studies showing that speech and voice therapy are beneficial for patients with voice alterations but with intact laryngeal nerves. While recurrent laryngeal nerve (RLN) paralysis can be evaluated by objective exams postoperatively, we are still left with the issue of possible partial or complete external branch of superior laryngeal nerve (EBSLN) injury. It is therefore quite difficult to segregate neural (RLN and EBSLN) and non-neural voice change populations, regardless of the method of literature evaluation. Perhaps patients' perspectives on how they experience voice functionality should play a superior role in deciding which patients should be investigated further with laryngoscopy, acoustic or perceptual analysis, and which patients should be offered treatment.

Suprascapular nerve injury after reverse total shoulder arthroplasty. Correlation with screw out of vault penetration and functional situation. Prospective study.

Baseplate screws have been suggested as a possible cause of suprascapular neuropathy after reverse total shoulder arthroplasty (RTSA). This study aims to investigate the association between screw penetration out of the vault, electromyographic study and the clinical outcomes. 31 patients who underwent RTSA for cuff tear arthropathy were prospectively enrolled. They were followed up for a minimum of 24 months. All underwent computed tomography 6 months postoperatively in order to determine the extraosseous position of the screws (perforation of the second bone cortex and protrusion into the supra or infraspinatus fossa). Electrodiagnostic evaluation was performed preoperatively and postoperatively to stablish any relation between cortex perforation of the screw and SSN injury. Clinical outcomes pre and postoperatively (Constant score, ranges of motion, and VAS) of patients with and without documented injury were recorded. 14 patients (45.2%) had abnormal preoperative SSN electrodiagnostic study (chronic or disuse injuries) and 6 patients (19.4%) abnormal postoperative study (acute injury. Of these last 6 patients: 2 cases appeared over the pre-existing lesion and 4 appeared over an intact preoperative nerve, all of them affecting the infraspinatus branch of the SSN. Perforation of the second cortex was detected for 60% of superior screws and 40% of posterior screws. The mean lengths of the superior and posterior screws were 30 and 18.2 mm, respectively. Patients with screw perforation of the second cortex were assessed as having a high risk of nerve injury (40% vs. 9.5%). Preoperative SSN injuries do not have a significant clinical impact and do not predispose to an acute postoperative SSN lesion. The Constant Score and VAS scale for patients with acute SSN injuries were not statistically different than those without SSN injury. Extraosseous position of the screw increases the probability of a SSN injury to 31%. This risk is higher with the posterior screw, which leads us to question whether it is really necessary to use it.

A multivariate physiological model of vagus nerve signalling during metabolic challenges in anaesthetised rats for diabetes treatment

Objective. This study aims to develop a comprehensive decoding framework to create a multivariate physiological model of vagus nerve transmission that reveals the complex interactions between the nervous and metabolic systems. Approach. Vagus nerve activity was recorded in female Sprague-Dawley rats using gold hook microwires implanted around the left cervical vagus nerve. The rats were divided into three experimental cohorts (intact nerve, ligation nerve for recording afferent activation, and ligation for recording efferent activation) and metabolic challenges were administered to change glucose levels while recording the nerve activity. The decoding methodology involved various techniques, including continuous wavelet transformation, extraction of breathing rate (BR), and correlation of neural metrics with physiological signals. Main results. Decrease in glucose level was consistently negatively correlated with an increase in the firing activity of the intact vagus nerve that was found to be conveyed by both afferent and efferent pathways, with the afferent response being more similar to the one on the intact nerve. A larger variability was observed in the sensory and motor responses to hyperglycaemia. A novel strategy to extract the BR over time based on inter-burst-interval is also presented. The vagus afferent was found to encode breathing information through amplitude and firing rate modulation. Modulations of the signal amplitude were also observed due to changes in heart rate in the intact and efferent recordings, highlighting the parasympathetic control of the heart. Significance. The analytical framework presented in this study provides an integrative understanding that considers the relationship between metabolic, cardiac, and breathing signals and contributes to the development of a multivariable physiological model for the transmission of vagus nerve signals. This work progresses toward the development of closed-loop neuro-metabolic therapeutic systems for diabetes.

Modulation of the tissue composition of regenerative neuroma by dexamethasone and granulocyte colony-stimulating factor

Aim. To evaluate the change of the content of mesenchymal (vimentin-positive) and reparative Schwann (GFAP-positive) cells in the regenerative neuroma of the rat sciatic nerve, taking into account the activity of local homeostasis regulation (CD73 expression) under the influence of dexamethasone (Dex) and granulocyte colony-stimulating factor (GCSF). Materials and methods. Vimentin-, GFAP-, and CD73-positive cells were detected immunohistochemically in the regenerative neuroma of 168 male Wistar rats, and their presence was quantified using statistical methods. Results. The regenerative neuroma of the sciatic nerve is characterized by a stereotypical cellular composition kinetics. Dexamethasone, during the initial stage of neuroma formation (1–7 days), led to a reduction in inflammatory infiltration and accumulation of vimentin+ mesenchymal cells. It significantly accelerated the accumulation of neural GFAP+ reparative Schwann cells and suppressed the expression of CD73. The granulocyte colony-stimulating factor (1–3 days) in the regenerative neuroma resulted in a slight reduction in inflammatory infiltration and an increase in the number of blood vessels penetrating into it. Under these conditions, the speed and quantity of vimentin+ cell accumulation and CD73 expression noticeably increased, as well as the speed of GFAP+ cell accumulation. The deviations in the expression of vimentin, GFAP, and CD73 in the neuroma under the administration of the mentioned substances gradually decreased and, after 8 weeks of the experiment, did not differ significantly from the control. When combined, dexamethasone and granulocyte colony-stimulating factor potentiated each other’s effects and, in addition, led to long-term maintenance of high CD73 expression. At the same time, the most pronounced approximation of the structure of the newly formed part of the nerve to the structure of the intact nerve trunk was observed. Conclusions. The simultaneous action of Dex and GCSF during the initial stages of regenerative neuroma formation, in contrast to their individual actions, not only alters the dynamics of mesenchymal and neural cell accumulation but also modifies the newly formed part of the nerve, bringing its structure closer to the intact state. This phenomenon is accompanied by increased reactivity of neurolemocytes during the axial cylinder germination stage of neuroma regeneration.

On-site detection and laboratory verification of the presence of nerve agent biomarkers using dried blood spots

The analysis of biomedical samples is important for the investigation of the alleged exposure to chemical warfare agents. The present study aims to use dried blood spots for portable detection and laboratory verification of organophosphate poisoning. After in-vitro incubation of blood with Novichok A-230, A-232 and A-234 and sarin, a volume of 25 and 50 µL was spotted on a protein saver card. Subsequently, the dried spots were extracted and analyzed by a mobile cholinesterase test kit. In addition, butyrylcholinesterase (BChE) was isolated and digested by pepsin followed by analysis with liquid chromatography tandem mass spectrometry (LC-MS/MS). The fluoride-activated samples were analyzed by gas chromatography tandem mass spectrometry (GC–MS/MS) and LC-MS/MS. It was found that the CWA induced cholinesterase inhibition was remarkably stable in dried blood spots. Even after at least one month storage under ambient conditions, the same linear reduction was visible as function of nerve agent exposure. Additionally, nonapeptide adducts were identified by LC-MS/MS one month after exposure. Also, intact Novichok nerve agents and regenerated sarin were observed by GC–MS/MS. In addition to the stability of the sample, important benefits of the proposed method include the less invasive sample collection and safer and easier shipping and storage conditions. In conclusion, this study shows the feasibility of using on-site detection and state-of-the-art laboratory analysis of dried blood spots for unambiguous verification of nerve agent exposure.

Impedance spectroscopy of enlarged cochlear implant stimulation electrodes – FEM simulations considering the perilymph

Abstract Cochlear implants are hearing prostheses for patients with severe to total hearing loss but intact auditory nerve. An external speech processor captures sound from the environment, which is subsequently converted into electrical signals and transmitted to an electrode array in the patient’s inner ear. The metallic stimulation electrodes of the electrode array electrically stimulate the spiral ganglion cells of the auditory nerve. The functionality of cochlear implants strongly depends on the possible maximum current stimulating the spiral ganglion cells, which can be affected by, e.g., cell growth around the stimulation electrodes. This in turn decreases the stimulation efficiency leading to decreased hearing. Cell growth, implant position and other changes in the surrounding medium are reflected in a change of the impedance of the stimulation electrodes. The impedance measurement of the stimulation electrodes is already implemented in all common cochlear implant systems to check functionality of the stimulation electrodes after implantation, but the frequency spectrum is normally not analyzed. Although this method can detect cell growth on the stimulation electrodes, it faces limitations when other interfering effects, such as changes in the perilymph and implant position, influence the impedance. This work shows impedance spectroscopic measurements using enlarged cochlear implant models to electrically analyze the surrounding medium, the perilymph, to understand changes in electrode impedance and to later monitor the stimulation efficiency of cochlear implants and to identify possible reasons for decreased hearing ability by impedance spectroscopy. In addition, we use FEM simulations to numerically model the influence of the perilymph composition on the impedance measurement. As shown by a final validation, this model can serve as a basis for an extended simulation model including implant position and cell growth monitoring to predict hearing deterioration in cochlear implant patients. In this context, this work serves as a basis for the development of a holistic prediction model and considers in the first step exclusively the influence of the perilymph composition on the impedance between two stimulation electrodes.

A Comparison of Outcomes between the Wiltse Approach with Pedicle Screw Fixation and the Percutaneous Pedicle Screw Fixation for Multi-Segmental Thoracolumbar Fractures.

Multi-segmental thoracolumbar fracture (MSF) generally refers to fractures occurring in two or more segments of the thoracolumbar spine. With the development of minimally invasive concept, there is little research on its application in the field of MSF. The purpose of this study is to compare two minimally invasive surgical techniques and determine which one is more suitable for treating patients with neurologically intact MSF. We retrospectively analyzed the clinical data of 49 MSF patients with intact nerves who were admitted from January 2017 to February 2019. Among them, 25 cases underwent percutaneous pedicle screw fixation (PPSF), and 24 cases underwent Wiltse approach pedicle screw fixation (WAPSF). The operation time, number of fixed segments, blood loss, length of incision, postoperative ambulation time, accuracy of pedicle screw placement, facet joint violation (FJV), number of C-arm exposures, as well as pre- and postoperative visual analogue scale (VAS), Oswestry disability index (ODI), local Cobb's angle (LCA), and percentage of anterior vertebral body height (PAVBH) were recorded for both groups. Paired sample t-test was used for intra-group comparison before and after surgery while independent sample t-test was used for inter-group comparison. The differences in the number of fixed segments, intraoperative bleeding, postoperative bed time, accuracy rate of pedicle screw placement, VAS, and ODI between the two groups were not statistically significant (p > 0.05). However, the operative time and total surgical incision length were significantly shorter in the WAPSF group than in the PPSF group (p < 0.05), and the FJV was significantly higher in the PPSF group than in the WAPSF group (p < 0.05). Also, the PPSF group received more intraoperative fluoroscopy (p < 0.05). The result of LCA and PAVBH in the WAPSF group were significantly better than in the PPSF group (p < 0.05). Both PPSF and WAPSF were found to be safe and effective in the treatment of MSF without neurological deficits through our study. However, considering radiation exposure, FJV, vertebral height restoration, correction of kyphosis, and learning curve, WAPSF may be a better choice for neurologically intact MSF.

Clinical Predictors of C5 Spinal Nerve Viability in Pan-Brachial Plexus Injuries.

In pan-brachial plexus injury, distinguishing between preganglionic and postganglionic injuries is crucial to reconstructive planning. This study aimed to identify preoperative factors that would accurately predict a reconstructible C5 spinal nerve. Patients with pan-brachial plexus injury from a single institution between 2001 and 2018 were reviewed. Patient demographics, clinical examination, diagnostic imaging, and electrodiagnostic results were recorded. C5 viability was determined based on supraclavicular exploration and intraoperative electrophysiologic testing. Univariate analysis identified significant factors for regression analysis. A multivariable parsimonious model was created using stepwise high-performance logistic regression. A total of 311 patients (mean age, 29.9 years; 46 women and 265 men; mean Injury Severity Score, 17.2) were included. A total of 134 patients (43%) had a viable C5 nerve, and 50 patients (12%) had a viable C6 nerve. Intact C5 spinal nerve on computed tomographic (CT) myelogram (OR, 5.4), positive Tinel test (OR, 2.6), muscle strength greater than or equal to 4 (according to the modified British Medical Research Council scale) for the rhomboid (OR, 1.3) or greater than or equal to 4 for the serratus anterior (OR, 1.4), and rhomboid needle electromyography (OR, 1.8) were predictive of having a viable C5 spinal nerve. The multivariable parsimonious stepwise model (area under the curve, 0.77) included four factors: positive Tinel test, intact C5 spinal nerve on CT myelogram, hemidiaphragmatic elevation, and midcervical paraspinal fibrillations. In this cohort of pan-brachial plexus patients with major polytrauma, there was a 43% incidence of viable C5 spinal nerve. A positive Tinel test (OR, 2.1) and intact C5 spinal nerve on CT myelogram (OR, 4.9) predicted a viable C5 nerve. In contrast, hemidiaphragmatic elevation (OR, 3.1) and midcervical paraspinal fibrillations (OR, 2.92) predicted root avulsion. Risk, III.

Erythropoietin Protects against Retinal Damage in A Rat Model of Optic Neuropathy via Glial Suppression.

Traumatic optic neuropathy (TON) causes partial or complete blindness because death of irreplaceable retinal ganglion cells (RGCs). Neuroprotective functions of erythropoietin (EPO) in the nervous system have been considered by many studies investigating effectiveness of this cytokine in various retinal disease models. It has been found that changes in retinal neurons under conditions of glial cells are effective in vision loss, therefore, the present study hypothesized that EPO neuroprotective effect could be mediated through glial cells in TON model. In this experiment study, 72 rats were assessed in the following groups: intact and optic nerve crush which received either the 4000 IU EPO or saline. Visual evoked potential and optomotor response and RGC number were assessed and regenerated axons evaluated by anterograde test. Cytokines gene expression changes were compared by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Density of astrocytes cells, assessed by fluorescence intensity, in addition, possible cytotoxic effect of EPO was measured on mouse astrocyte culture in vitro. in vitro data showed that EPO was not toxic for mouse astrocytes. Intravenous injection of EPO improved vision, in terms of visual behavioral tests. RGCs protection was more than two times in EPO, compared to the vehicle group. More regenerated axons were determined by anterograde tracing in the EPO group compared to the vehicle. Moreover, GFAP immunostaining showed while the intensity of reactive astrocytes was increased in injured retina, systemic EPO decreased it. In the treatment group, expression of GFAP was down-regulated, while CNTF was upregulated as assessed by qRT-PCR in the 60th day post-crush. Our study showed that systemic administration of EPO can protect degenerating RGCs. Indeed, exogenous EPO exerted neuroprotective and neurotrophic functions by reducing reactive astrocytic gliosis. Therefore, reduction of gliosis by EPO may be considered as therapeutic targets for TON.

Electrical promontory stimulation test using a portable peripheral nerve stimulator with an ear canal electrode

ObjectiveAn intact cochlear nerve is necessary for successful cochlear implantation (CI). Although the promontory stimulation test (PST) using a promontory stimulator (PS) and a transtympanic needle electrode is invasive, it is still commonly used to verify cochlear nerve function. PSs are currently unavailable because they are no longer manufactured; however, considering that PST continues to be beneficial in certain situations, alternative equipment is needed. The PNS-7000® (PNS) was developed as a neurologic instrument for stimulating the peripheral nerves. This study investigated the usefulness of the ear canal stimulation test (ECST) using PNS with a silver ball ear canal electrode, which is a new noninvasive alternative technique to the PST. MethodsECST was performed from November 2013 to December 2018 using PS and PNS for patients with severe to profound sensorineural hearing loss. The electrical threshold, most comfortable loudness level, uncomfortable loudness level, dynamic range, and gap detection were measured in the ECST. The results of these measured PNS items were compared with PS. ResultsECST was performed in 61 ears of 35 patients (age, 59.9 ± 20.1 years) using PS and PNS. The sound sensation was elicited in 51 (83.6%) and 52 (85.2%) ears with PS and PNS, respectively. All items excluding GAP were measured in 46 (75%) and 43 (70%) ears at 50 and 100 Hz, respectively. GAP was measured in 33 ears by the ascending and descending methods using PS and PNS. Spearman's rank-order correlation coefficient revealed a significant positive linear correlation between the PS and PNS results in all measurements. No significant difference was found between the PS and PNS thresholds in all measured items. ConclusionsPNS is a useful instrument for performing ECST as a new alternative to PS. ECST using a silver ball electrode is a less invasive and easier test than PST.

Chronic Vagotomy Alters Glutamate Transmission in the Nucleus Tractus Solitarii (nTS)

The nTS is the first site of integration and processing of sensory afferent information and is one of the crucial brainstem nuclei involved in cardiorespiratory reflexes. This nucleus receives afferent information from many visceral structures in the thorax and abdomen via the peripheral branches of the vagus nerve. Vagal afferents release glutamate (Glu) which initiates signaling processes that leads to chemo- and baroreflex-mediated changes in sympathetic and phrenic nerve activity. Previous studies by us have shown that decreasing afferent input via unilateral vagotomy augmented nTS astrocyte complexity. Astrocytes contribute to regulation of Glu concentration by removing Glu from the synaptic cleft via excitatory amino acid transporters (EAATs). We hypothesized that vagotomy attenuates Glu signaling in the nTS due to increased Glu uptake by greater EAAT expression or function. Surgical transection or sham surgery of the right cervical vagus nerve caudal to the nodose ganglion was performed in male Sprague-Dawley rats. One week after surgery, mean arterial pressure (MAP), heart rate (HR), and splanchnic sympathetic and phrenic nerve activity (SSNA and PhrNA) were recorded in anesthetized and ventilated rats. Intact vagus nerves and the right phrenic nerve were acutely transected. Nanoinjections of Glu (30 nl, 1-10 mM) into the nTS decreased MAP, HR, SSNA and PhNA in both sham and vagotomy groups. Vagotomy blunted the HR, SSNA and PhrNA responses, indicating that Glu signaling was attenuated. To determine if increased EAAT function contributed to blunted Glu responses, the EAAT blocker TFB-TBOA (10nM, 60nl) was nanoinjected into the nTS. EAAT blockade mimicked the effect of Glu, producing similar depressor, bradycardic, and apneic responses in both groups. TBOA also enhanced the cardiorespiratory responses to Glu injection in both groups. EAAT blockade did not restore Glu responses in the vagotomy group compared to sham. Taken together, these data suggest that increased EAAT function did not account for the attenuated Glu signaling in the nTS. Further studies are needed to uncover the mechanisms by which vagotomy affects Glu signaling in the nTS. NIH R01 HL098602 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.