Axis Of Nerve Research Articles

Three-dimensional molecular atlas highlights spatial and neurochemical complexity in the axial nerve cord of octopus arms

Octopus arms, notable for their complex anatomy and remarkable flexibility, have sparked significant interest within the neuroscience community. However, there remains a dearth of knowledge about the neurochemical organization of various cell types in the arm's nervous system. To address this gap, we used hybridization chain reaction (HCR) to identify distinct neuronal types in the axial nerve cords of the pygmy octopus, Octopus bocki, including putative dopaminergic, octopaminergic, serotonergic, GABAergic, glutamatergic, cholinergic, and peptidergic cells. We obtained high-resolution multiplexed fluorescent images at 0.28×0.28×1.0μm voxel size from 10 arm base and arm tip cross sections (each 50μm thick) and created three-dimensional reconstructions of the axial ganglia, illustrating the spatial distribution of multiple neuronal populations. Our analysis unveiled anatomically distinct and molecularly diverse scattered neurons, while also highlighting multiple populations of dense small neurons that appear uniformly distributed throughout the cortical layer and potential glial cells in the neuropil. Our data provide new insights into how different types of neurons may contribute to an octopus's ability to interact with its environment and execute complex tasks. In addition, our findings establish a benchmark for future studies, allowing pioneering exploration of octopus arm molecular neuroanatomy and offering exciting new avenues in invertebrate neuroscience research.

Relationships of the vidian nerve and internal carotid artery: MRI and intraoperative surgical evaluation.

Skull base anatomy around the internal carotid artery (ICA) is extremely complex. Among anatomical landmarks studied, the vidian canal has been thoroughly evaluated, unlike the vidian nerve (VN). Our aim is to evaluate the VN-ICA relationships, and understand their role in terms of surgical planning. Fifty MRI examinations of 100 healthy petro-spheno-clival regions were reviewed in order to evaluate the relationship between the vidian nerve axis (VNA) and the petrous ICA. Twenty-seven cases of expanded endonasal approaches to petrous apex region were evaluated to check the VN-ICA relationship intraoperatively. MRI evaluations showed that, in 23% of cases, the VNA was below the edge of the ICA, in 45% it was at the edge of the ICA and in 32% it ended up above the edge of the ICA. Surgically speaking, in 9 of 28 petrous apex approaches, the VN ended above the inferior edge of the petrous carotid. MRI evaluation adds useful information in planning the surgical approach to petro-spheno-clival regions, even if the identification of VNA, in these cases, may not be radiologically possible. Surgical experience confirms the importance of VN identification in guiding the surgeon in complex cases, and also outline the possible risks of relying only on this landmark.

Neuronal segmentation in cephalopod arms.

The prehensile arms of the cephalopod are among these animals' most remarkable features, but little is known about the neural circuitry governing arm and sucker movements1,2. Here, we investigated the cellular and molecular organization of the arm nervous system, focusing on the massive axial nerve cords (ANCs) in the octopus arms which collectively harbor four times as many neurons as the central brain3. We found that the ANC is segmented. In transverse cross sections, the ANC cell body layer wraps around the neuropil with no apparent segregation of sensory and motor neurons. In longitudinal sections, however, ANC neurons form segments, setting up a modular organization to the adjoining ANC neuropil. The septa between each segment are, in contrast, neuron-poor but contain nerve exits, vasculature and abundant collagen. Surprisingly, nerves exiting from neighboring septa differ in their fiber trajectories indicating that multiple adjoining segments must cooperate to innervate the arm musculature fully. The nerves for each sucker also exit through septa and set up a spatial "suckerotopy" in the ANC. A strong link between ANC segmentation and flexible sucker-laden arms was confirmed by comparative study of squid arms and tentacles. The ANC segmental modules represent a new template for understanding the motor control of octopus soft tissues. They also provide the first example of nervous system segmentation in a mollusc4.

Neuronal segmentation in cephalopod arms.

The prehensile arms of the cephalopod are among these animals most remarkable features, but the neural circuitry governing arm and sucker movements remains largely unknown. We studied the neuronal organization of the adult axial nerve cord (ANC) of Octopus bimaculoides with molecular and cellular methods. The ANCs, which lie in the center of every arm, are the largest neuronal structures in the octopus, containing four times as many neurons as found in the central brain. In transverse cross section, the cell body layer (CBL) of the ANC wraps around its neuropil (NP) with little apparent segregation of sensory and motor neurons or nerve exits. Strikingly, when studied in longitudinal sections, the ANC is segmented. ANC neuronal cell bodies form columns separated by septa, with 15 segments overlying each pair of suckers. The segments underlie a modular organization to the ANC neuropil: neuronal cell bodies within each segment send the bulk of their processes directly into the adjoining neuropil, with some reaching the contralateral side. In addition, some nerve processes branch upon entering the NP, forming short-range projections to neighboring segments and mid-range projections to the ANC segments of adjoining suckers. The septa between the segments are employed as ANC nerve exits and as channels for ANC vasculature. Cellular analysis establishes that adjoining septa issue nerves with distinct fiber trajectories, which across two segments (or three septa) fully innervate the arm musculature. Sucker nerves also use the septa, setting up a nerve fiber "suckerotopy" in the sucker-side of the ANC. Comparative anatomy suggests a strong link between segmentation and flexible sucker-laden arms. In the squid Doryteuthis pealeii, the arms and the sucker-rich club of the tentacles have segments, but the sucker-poor stalk of the tentacles does not. The neural modules described here provide a new template for understanding the motor control of octopus soft tissues. In addition, this finding represents the first demonstration of nervous system segmentation in a mollusc.

The pulmonary neuroepithelial body-vagal sensory nerve axis is altered in a mouse model of bronchopulmonary dysplasia (BPD)

Breathing control problems, like apnea of prematurity, are a common complication in preterm infants with bronchopulmonary dysplasia (BPD), but the underlying factors remain incompletely understood. A subpopulation of pulmonary vagal afferent nerve fibers (Calb1+) innervate CO2 and O2 sensitive clusters of lung neuroendocrine cells (neuroepithelial bodies (NEBs)) located along conducting airways. Calb1+ fibers provide direct sensory input to the brainstem that putatively limit tidal volume. NEBs are hyperplastic in BPD infants and may increase activity of inhibitory Calb1+ vagal fibers. Herein, we sought to determine if the NEB-Calb1 lung-brainstem axis is altered in association with breathing control in BPD. BPD in mice was established by exposure to chronic neonatal (postnatal day (P) 0-14) hyperoxia (Hx; 70% O2; n=20) or normoxia (Nx; n=17). Consistent with human BPD, Hx caused alveolar simplification supported by a reduction in alveolar density and alveoli (p<0.05; separate t-tests) in P22 H&E-stained lung sections (n=5-7/group). Like human infants at risk for BPD, Hx mice adapted to increased dead space (caused by reduction in alveoli) by hyperventilating (p<0.05; generalized linear modeling accounting for fat free mass and heat production, measured by NMR and respirometry; n=10-24/group). This was facilitated by an increase in tidal volume that was significantly reduced at P14 but increased at P17 and P21 (n=19-28) (Tukey’s post-hoc: p<0.05). NEBs and associated innervation (vagal and dorsal root ganglia) were next assessed in subsets of mice. First, IT instillation of WGA-594 lectin into subsets of mice (n=9 mice/18 ganglia per group) and subsequent quantification of 594+ neurons per vagal ganglia revealed fewer neurons (p=0.07; t-test) in Hx mice (110.8 ± 6.9 vs 95.2 ± 4.9). Second, CGRP+ innervation to NEBs is reduced in Hx mice (Quantification of CGRP+ nerve fibers only: 17740.4 +/- 4126 vs 10474.6 +/- 2140 +CGRP pixels; p=0.12 n=5-7/group). Third, there was greater frequency of NEBs per unit airway (p<0.05; 0.306 ± 0.03 vs 0.401 ± 0.03) with a tendency for larger NEBs (p=0.06; 9.14 ± 0.7 vs 11.93 ± 1.3) indicating NEB hyperplasia. Together, these data indicate individual NEB innervation is reduced in BPD but that total NEB innervation may remain unchanged. If this is true for Calb1+ vagal fibers remain untested. To functionally assess Calb1-vagal fibers we activated, with DCZ, the excitatory synthetic Gq-DREAD receptor (DTR) expressed in Calb1cre mice via microinjection of AAV-Cre-Gq-mCherry into the left vagal ganglia. DCZ but not vehicle caused a major increase in peak inspiratory flow during acute hypoxic challenges compared to vehicle treated mice (Pre-DMSO, Post-DMSO, Pre-DCZ = ~1ml/sec vs 4ml/sec post-DCZ; p<0.05, n=4/group). Collection of vagal ganglia confirms DTR expression but spillover of DTR is present. Repeating these studies with diluted AAV-Cre-Gq in control and BPD mice are ongoing. Together, our data verify that hyperoxia induced BPD in mice causes a similar reduction in alveoli and compensation to increased dead space by hyperventilation as observed in human BPD. Additionally, BPD structurally alters the NEB-vagal axis but whether these changes are functionally significant to nCOB is being addressed with ongoing studies. AHA 20CDA35310121, Advancing Healthier Wisconsin Endowment. This is the full abstract presented at the American Physiology Summit 2024 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.

Improved optic nerve visualization and treatment planning through a dedicated optic nerve MRI protocol.

This study describes an innovative optic nerve MRI protocol for better delineating optic nerve anatomy from neighboring pathology. Twenty-two patients undergoing MRI examination of the optic nerve with the dedicated protocol were identified and included for analysis of imaging, surgical strategy, and outcomes. T2-weighted and fat-suppressed T1-weighted gadolinium-enhanced images were acquired perpendicular and parallel to the long axis of the optic nerve to achieve en face and in-line views along the course of the nerve. Dedicated optic nerve MRI sequences provided enhanced visualization of the nerve, CSF within the nerve sheath, and local pathology. Optic nerve sequences leveraged the "CSF ring" within the optic nerve sheath to create contrast between pathology and normal tissue, highlighting areas of compression. Tumor was readily tracked along the longitudinal axis of the nerve by images obtained parallel to the nerve. The findings augmented treatment planning. The authors present a dedicated optic nerve MRI protocol that is simple to use and affords improved cross-sectional and longitudinal visualization of the nerve, surrounding CSF, and pathology. This improved visualization enhances radiological evaluation and treatment planning for optic nerve lesions.

‘Arm brains’ (axial nerves) of Jurassic coleoids and the evolution of coleoid neuroanatomy

Although patchy, the fossil record of coleoids bears a wealth of information on their soft part anatomy. Here, we describe remains of the axial nerve cord from both decabrachian (Acanthoteuthis, Belemnotheutis, Chondroteuthis) and octobrachian (Plesioteuthis, Proteroctopus, Vampyronassa) coleoids from the Jurassic. We discuss some hypotheses reflecting on possible evolutionary drivers behind the neuroanatomical differentiation of the coleoid arm crown. We also propose some hypotheses on potential links between habitat depth, mode of life and the evolution of the Coleoidea.

Huangqi Guizhi Wuwu decoction alleviates oxaliplatin-induced peripheral neuropathy via the gut-peripheral nerve axis

BackgroundOxaliplatin-induced peripheral neurotoxicity (OIPN) limits the dose of chemotherapy and seriously affects the quality of life. Huangqi Guizhi Wuwu Decoction (HGWD) is a classical Traditional Chinese Medicine (TCM) formula for the prevention of OIPN. However, its specific pharmacological mechanism of action remains unknown. Our study found that HGWD can effectively alleviate chronic OIPN and regulate intestinal flora. Therefore, we explored the mechanism of action of HGWD in alleviating chronic OIPN from the perspective of intestinal flora.MethodsIn this study, we established an OIPN model in C57BL/6 mice treated with different concentrations of HGWD. Mechanical pain and cold pain were assessed at certain time points, and samples of mice colon, dorsal root ganglion (DRG), serum, and feces were collected. Associated inflammation levels in the colon and DRG were detected using immunohistochemical techniques; the serum lipopolysaccharide (LPS) levels and associated inflammation were assessed using the appropriate kits; and 16S rRNA sequencing was used to examine the dynamic changes in gut microorganisms. Finally, established fecal microbiota transplantation (FMT) and antibiotic (ABX) pretreatment models were used to validate flora’s role in HGWD for chronic OIPN by pain scoring and related pathological analysis.ResultsHGWD treatment significantly alleviated pain sensitivity in chronic OIPN mice. Pathological results showed that HGWD treatment improved intestinal ZO-1 expression and reduced serum LPS levels and associated inflammatory factors in the colon, serum, and DRG. The 16S rRNA results showed that HGWD restored the composition of the intestinal flora in a time-dependent manner to alleviate OIPN. FMT and ABX experiments demonstrated that HGWD can alleviate chronic OIPN by regulating intestinal flora homeostasis.ConclusionsHGWD prevents chronic OIPN by dynamically regulating intestinal flora homeostasis, thereby ameliorating intestinal barrier damage and reducing serum LPS and relevant inflammatory factor levels in the colon, serum, and DRG.

Management of Proptosis in a Case of Sphenoid-Orbital Meningioma

Sphenoid-orbital meningiomas (SOMs) are difficult to completely resect because they involve the sphenoid wing, orbit, and cavernous sinus. As the tumor invades the optic canal, SOMs frequently present with visual deficits. The authors of this case report dealt with the case of a 65-year-old male patient who had right-sided proptosis. We diagnosed the patient, and his MRI revealed of him having SOM. The surgical approach was determined by the tumor's placement in the orbit and cranial cavity and its connections to the optic canal and optic nerve axis. Tumor was removed successfully by surgery. The patient retained a proptosis of less than 4 mm during the follow-up period. The visual acuity, visual field, and ocular fundus were examined during the follow-up. SOMs are notoriously difficult to treat surgically. The primary goal of surgery in symptomatic individuals with SOMs is to slow down the tumor's progression. Longer periods of post-operative follow-up is recommended to observe long-term results. Bang. J Neurosurgery 2022; 12(1): 65-68

Diabetes Insipidus Pascaoperasi pada Pasien dengan Reseksi Tumor Kraniofaringioma

Craniopharyngioma is an embryonic malformation in the sella and parasella areas. Craniopharyngioma has high survival rate, although the patient's quality of life is often compromised due to tumor’s location near important anatomical structures such as the optic nerve, optic chiasm, and hypothalamic-pituitary axis. Craniopharyngioma tumor resection can provoke diabetes insipidus. Diabetes insipidus (DI) is characterized by polyuria, dehydration and hypernatremia due to vasopressin or antidiuretic hormone (ADH) deficiency. A 20 years old male patient complained of polyuria, paresthesia in both hands, rapid body growth, and headaches. Brain magnetic resonance imaging (MRI) with contrast revealed cystic mass in the parasella cistern region suggested craniopharyngioma. This patient underwent craniotomy tumor resection under general anesthesia and additional scalp block. Postoperatively the patient experienced an increased urine volume up to 400 ml/hour and fluid replacement was performed with crystalloids Ringerfundin and D5 ¼ NS. The patient suffered DI and vasopressin was continued in the postoperative period until urine output reduced to <2 ml/kg/hour. Perioperative management of craniopharyngioma is controlling intracranial pressure, prevent secondary brain injury and postoperative monitoring in the intensive care unit to manage potential complications such as DI. In this case, patient suffered polyuria and increased plasma sodium levels which was safely treated by administration of vasopressin and rehydration to maintain fluid adequacy and balance of plasma sodium levels

Safety of continuous intraoperative vagus nerve neuromonitoring during thyroid surgery.

Continuous intraoperative neuromonitoring has successfully demonstrated to predict impending damage to the recurrent laryngeal nerve, by detecting changes in electromyographic recordings. Despite the apparent benefits associated with continuous intraoperative neuromonitoring, its safety is still a debate. The aim of this study was to investigate the electrophysiological impact of continuous intraoperative neuromonitoring on the vagus nerve. In this prospective study, the amplitude of the electromyographic wave of the vagus nerve-recurrent laryngeal nerve axis was measured both proximally and distally to the stimulation electrode placed upon the vagus nerve. Electromyographic signal amplitudes were collected at three distinct events during the operation: during the dissection of the vagus nerve, before application of the continuous stimulation electrode onto the vagus nerve and after its removal. In total, 169 vagus nerves were analysed, among 108 included patients undergoing continuous intraoperative neuromonitoring-enhanced endocrine neck surgeries. Electrode application resulted in a significant overall decrease in measured proximo-distal amplitudes of -10.94 µV (95 per cent c.i. -17.06 to -4.82 µV) (P < 0.005), corresponding to a mean(s.d.) decrease of -1.4(5.4) per cent. Before the removal of the electrode, the measured proximo-distal difference in amplitudes was -18.58 µV (95 per cent c.i. -28.31 to -8.86 µV) (P < 0.005), corresponding to a mean(s.d.) decrease of -2.50(9.59) per cent. Seven nerves suffered a loss of amplitude greater than 20 per cent of the baseline measurement. In addition to supporting claims that continuous intraoperative neuromonitoring exposes the vagus nerve to injury, this study shows a mild electrophysiological impact of continuous intraoperative neuromonitoring electrode placement on the vagus nerve-recurrent laryngeal nerve axis. However, the small observed differences are negligible and were not associated with a clinically relevant outcome, making continuous intraoperative neuromonitoring a safe adjunct in selected thyroid surgeries.

Mechanosensory signal transmission in the arms and the nerve ring, an interarm connective, of Octopus bimaculoides

Octopuses coordinate their arms in a range of complex behaviors. In addition to brain-based sensorimotor integration and control, interarm coordination also occurs through a nerve ring at the arms' base. Here, we examine responses to mechanosensory stimulation of the arms by recording neural activity in the stimulated arm, the nerve ring, and other arms in a preparation of only the ring and arms. Arm axial nerve cords show graded responses to mechanosensory input and activity is transmitted proximally and distally in the arm. Mechanostimulation of one arm generates spiking in the nerve ring and in other arms. Activity in the nerve ring decreases with distance from the stimulated arm. Spontaneous activity with a range of spiking patterns occurs in the axial nerve cords and the nerve ring. These data show rich interarm signaling that supports arm control and coordination occurring outside of the brain.

Noninvasive intracranial pressure assessment by optic nerve sheath diameter: Automated measurements as an alternative to clinician-performed measurements.

Optic nerve sheath diameter (ONSD) has shown promise as a noninvasive parameter for estimating intracranial pressure (ICP). In this study, we evaluated a novel automated method of measuring the ONSD in transorbital ultrasound imaging. From adult traumatic brain injury (TBI) patients with invasive ICP monitoring, bedside manual ONSD measurements and ultrasound videos of the optic nerve sheath complex were simultaneously acquired. Automatic ONSD measurements were obtained by the processing of the ultrasound videos by a novel software based on a machine learning approach for segmentation of the optic nerve sheath. Agreement between manual and automated measurements, as well as their correlation to invasive ICP, was evaluated. Furthermore, the ability to distinguish dichotomized ICP for manual and automatic measurements of ONSD was compared, both for ICP dichotomized at ≥20 mmHg and at the 50th percentile (≥14 mmHg). Finally, we performed an exploratory subgroup analysis based on the software's judgment of optic nerve axis alignment to elucidate the reasons for variation in the agreement between automatic and manual measurements. A total of 43 ultrasound examinations were performed on 25 adult patients with TBI, resulting in 86 image sequences covering the right and left eyes. The median pairwise difference between automatically and manually measured ONSD was 0.06 mm (IQR -0.44 to 0.38 mm; p = 0.80). The manually measured ONSD showed a positive correlation with ICP, while automatically measured ONSD showed a trend toward, but not a statistically significant correlation with ICP. When examining the ability to distinguish dichotomized ICP, manual and automatic measurements performed with similar accuracy both for an ICP cutoff at 20 mmHg (manual: AUC 0.74, 95% CI 0.58-0.88; automatic: AUC 0.83, 95% CI 0.66-0.93) and for an ICP cutoff at 14 mmHg (manual: AUC 0.70, 95% CI 0.52-0.85; automatic: AUC 0.68, 95% CI 0.48-0.83). In the exploratory subgroup analysis, we found that the agreement between measurements was higher in the subgroup where the automatic software evaluated the optic nerve axis alignment as good as compared to intermediate/poor. The novel automated method of measuring the ONSD on the ultrasound videos using segmentation of the optic nerve sheath showed a reasonable agreement with manual measurements and performed equally well in distinguishing high and low ICP.

MR microneurography of human peripheral fascicles using a clinical 3T MR scanner

Background and purposeKnowledge of nerve fascicular structures is essential for managing peripheral nerve disorders. This study aimed to investigate the feasibility of z-axis high-resolution magnetic resonance (MR) microneurography (zH-MRMN) in displaying the three-dimensional structures of tibial nerve fascicles in vivo using a 3T MR scanner. Materials and methodsTwelve volunteers underwent z-axis conventional-resolution MR microneurography (zC-MRMN) and zH-MRMN of tibial nerves. The visibility scores of the nerve fascicles (VSNFs) on axial zC-MRMN images and axial zH-MRMN multiplanar reformation (MPR) images were compared. The nerve fascicle appearances on the longitudinal zH-MRMN MPR images were described. ResultsIn the nerve segments whose long axes were perpendicular to the imaging planes of both zC-MRMN and zH-MRMN, the VSNFs were not significantly different between the axial images of the two modalities (P = 0.083). In the nerve segments whose long axes were not perpendicular to the imaging planes of zC-MRMN, the VSNFs on the axial zC-MRMN images were significantly lower than those on the axial zH-MRMN MPR images that were angled perpendicular to the long axis of the tibial nerve (P < 0.001). ConclusionsThe longitudinal zH-MRMN MPR images clearly displayed the changing features of the intraneural fascicles as well as the gross morphology of the tibial nerves. zH-MRMN can clearly delineate the topography of the tibial nerve fascicles in vivo through use of a 3T MR scanner.

Management of Proptosis in a Case of Sphenoid-Orbital Meningioma

Sphenoid-orbital meningiomas (SOMs) are difficult to completely resect because they involve the sphenoid wing, orbit, and cavernous sinus. As the tumor invades the optic canal, SOMs frequently appear with visual deficits. The authors of this case report dealt with the case of a 65-year-old male patient who had right-sided proptosis. We diagnosed the patient, and his MRI revealed of having SOMs. The surgical approach was determined by the tumor’s placement in the orbit and cranial cavity and its connections to the optic canal and optic nerve axis. Surgical excision was used to successfully remove the SOM. The patient maintained a proptosis of less than 4 mm during the follow-up period. The visual acuity, visual field, and ocular fundus were examined during the optical follow-up. SOMs are notoriously difficult to treat surgically. The primary goal of surgery in symptomatic individuals with SOMs is to slow down the tumor’s progression. Longer periods of post-operative observation and follow-up are recommended to observe long-term advantages. Bang. J Neurosurgery 2022; 11(2): 145-149

Segmental formation of the main nerves of the sacral plexus

The study of segmental innervation may be of practical interest, as pathological processes involving organs and tissues can be caused by damage to both peripheral and individual segmental nerves. Also, the occurrence of a pathological condition of the pelvic limb structures can be associated with various injuries, damage to the spinal cord, roots and segmental nerves of the sacral spine. The aim of the experimental research was to study the segmental formation of the main nerves of the sacral plexus – n. ischiadicus, n. tibialis, n. peroneus communis in cats. Unilateral extravertebral ganglioectomy of the lumbosacral segments – L 4, L5, L6, L7, S1, S2 was performed for the study. Samples of the main nerves were examined in polarized light to detect signs of Wallerian's degeneration at x400 magnification. This method allows you to easily distinguish degenerated nerve fibers at different stages of degeneration from normal. The micromorphology of the initial stages of degeneration is characterized by uneven thickening of the fibers, smoothing of the Ranvier nodes, dilated Schmidt-Lanterman notches, an increasein the number of myelin segments. At later stages of Wallerian's degeneration, the following are observed: edema and significant thickening of the myelin sheath, smoothing of fiber contours, formation of ovoids and fragmentary glow of myelin. Statistical analysis of the results was performed using Student's t-test. In the course of research, it was found that in the formation of the main nerves of the sacral plexus: n. ischiadicus, n. tibialis, n. peroneus communis involves 6 segments of the lumbosacral spine - from L4 to S2. These nerves of the sacral plexus are polysegmental, which indicates their compensatory properties. The highest percentage of degenerated nerve fibers for the main nerves of the sacral plexus gives the 6th lumbar segment L6, which is the axial nerve. The obtained results can expand the knowledge of principles of segmentation in anatomy, to become a reference point for sacral regional epidural anesthesia for orthopedic operations on the pelvic limbs, nerve blockade to increase patient comfort in the postoperative period, lumbar puncture, neurotherapy. The method of polarization microscopy can be used as a clinically useful test for peripheral nerve biopsy to assess the state of neurodegenerative changes, monitoring regenerative and neuroprotective effects. Key words: Wallerian degeneration, segmental innervation, sacral plexus, polarization microscopy, cats.

Ubiquitin-Specific Protease 2 in the Ventromedial Hypothalamus Modifies Blood Glucose Levels by Controlling Sympathetic Nervous Activation.

Ubiquitin-specific protease 2 (USP2) participates in glucose metabolism in peripheral tissues such as the liver and skeletal muscles. However, the glucoregulatory role of USP2 in the CNS is not well known. In this study, we focus on USP2 in the ventromedial hypothalamus (VMH), which has dominant control over systemic glucose homeostasis. ISH, using a Usp2-specific probe, showed that Usp2 mRNA is present in VMH neurons, as well as other glucoregulatory nuclei, in the hypothalamus of male mice. Administration of a USP2-selective inhibitor ML364 (20 ng/head), into the VMH elicited a rapid increase in the circulating glucose level in male mice, suggesting USP2 has a suppressive role on glucose mobilization. ML364 treatment also increased serum norepinephrine concentration, whereas it negligibly affected serum levels of insulin and corticosterone. ML364 perturbated mitochondrial oxidative phosphorylation in neural SH-SY5Y cells and subsequently promoted the phosphorylation of AMP-activated protein kinase (AMPK). Consistent with these findings, hypothalamic ML364 treatment stimulated AMPKα phosphorylation in the VMH. Inhibition of hypothalamic AMPK prevented ML364 from increasing serum norepinephrine and blood glucose. Removal of ROS restored the ML364-evoked mitochondrial dysfunction in SH-SY5Y cells and impeded the ML364-induced hypothalamic AMPKα phosphorylation as well as prevented the elevation of serum norepinephrine and blood glucose levels in male mice. These results indicate hypothalamic USP2 attenuates perturbations in blood glucose levels by modifying the ROS-AMPK-sympathetic nerve axis.SIGNIFICANCE STATEMENT Under normal conditions (excluding hyperglycemia or hypoglycemia), blood glucose levels are maintained at a constant level. In this study, we used a mouse model to identify a hypothalamic protease controlling blood glucose levels. Pharmacological inhibition of USP2 in the VMH caused a deviation in blood glucose levels under a nonstressed condition, indicating that USP2 determines the set point of the blood glucose level. Modification of sympathetic nervous activity accounts for the USP2-mediated glucoregulation. Mechanistically, USP2 mitigates the accumulation of ROS in the VMH, resulting in attenuation of the phosphorylation of AMPK. Based on these findings, we uncovered a novel glucoregulatory axis consisting of hypothalamic USP2, ROS, AMPK, and the sympathetic nervous system.

Diagnosis of Cubital Tunnel Syndrome Using Deep Learning on Ultrasonographic Images.

Although electromyography is the routine diagnostic method for cubital tunnel syndrome (CuTS), imaging diagnosis by measuring cross-sectional area (CSA) with ultrasonography (US) has also been attempted in recent years. In this study, deep learning (DL), an artificial intelligence (AI) method, was used on US images, and its diagnostic performance for detecting CuTS was investigated. Elbow images of 30 healthy volunteers and 30 patients diagnosed with CuTS were used. Three thousand US images were prepared per each group to visualize the short axis of the ulnar nerve. Transfer learning was performed on 5000 randomly selected training images using three pre-trained models, and the remaining images were used for testing. The model was evaluated by analyzing a confusion matrix and the area under the receiver operating characteristic curve. Occlusion sensitivity and locally interpretable model-agnostic explanations were used to visualize the features deemed important by the AI. The highest score had an accuracy of 0.90, a precision of 0.86, a recall of 1.00, and an F-measure of 0.92. Visualization results show that the DL models focused on the epineurium of the ulnar nerve and the surrounding soft tissue. The proposed technique enables the accurate prediction of CuTS without the need to measure CSA.

Unbiased immune profiling reveals a natural killer cell-peripheral nerve axis in fibromyalgia.

The pathophysiology of fibromyalgia syndrome (FMS) remains elusive, leading to a lack of objective diagnostic criteria and targeted treatment. We globally evaluated immune system changes in FMS by conducting multiparametric flow cytometry analyses of peripheral blood mononuclear cells and identified a natural killer (NK) cell decrease in patients with FMS. Circulating NK cells in FMS were exhausted yet activated, evidenced by lower surface expression of CD16, CD96, and CD226 and more CD107a and TIGIT. These NK cells were hyperresponsive, with increased CCL4 production and expression of CD107a when co-cultured with human leukocyte antigen null target cells. Genetic and transcriptomic pathway analyses identified significant enrichment of cell activation pathways in FMS driven by NK cells. Skin biopsies showed increased expression of NK activation ligand, unique long 16-binding protein, on subepidermal nerves of patients FMS and the presence of NK cells near peripheral nerves. Collectively, our results suggest that chronic activation and redistribution of circulating NK cells to the peripheral nerves contribute to the immunopathology associated with FMS.

Quantification of Optic Nerve Cross Sectional Area on MRI: A Novel Protocol using Fiji Software.

Optic nerve assessment is an important aspect of glaucoma diagnosis and follow-up. This project describes a protocol for a unified methodology of optic nerve cross-sectional assessment and quantification using 3 T MRI for image acquisition and ImageJ's Fiji software for image processing quantification. Image acquisition was performed using 3 T MRI, with proper instructions for the patient to ensure straight fixation during imaging. A T2-weighted fat suppressed sequence was used. A coronal cut taken 3 mm behind the globe and perpendicular to the optic nerve axis should be uploaded to the software. Using the threshold function, the white matter area of the optic nerve is selected and quantified, thus, eliminating inter-individual measurement bias. We also described the normal limits for the optic nerve cross-sectional area according to age, based on previously published literature. We used the described protocol to assess optic nerve of a suspected glaucoma patient. The optic nerve cross-sectional area was found to be within the normal limits, a finding further confirmed via optical coherence tomography of the optic nerve.