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PloS One 2024Orexin-mediated stimulation of orexin receptors 1/2 (OX[1/2]R) may stimulate the diaphragm and genioglossus muscle via activation of inspiratory neurons in the...
Orexin receptor 2 agonist activates diaphragm and genioglossus muscle through stimulating inspiratory neurons in the pre-Bötzinger complex, and phrenic and hypoglossal motoneurons in rodents.
Orexin-mediated stimulation of orexin receptors 1/2 (OX[1/2]R) may stimulate the diaphragm and genioglossus muscle via activation of inspiratory neurons in the pre-Bötzinger complex, which are critical for the generation of inspiratory rhythm, and phrenic and hypoglossal motoneurons. Herein, we assessed the effects of OX2R-selective agonists TAK-925 (danavorexton) and OX-201 on respiratory function. In in vitro electrophysiologic analyses using rat medullary slices, danavorexton and OX-201 showed tendency and significant effect, respectively, in increasing the frequency of inspiratory synaptic currents of inspiratory neurons in the pre-Bötzinger complex. In rat medullary slices, both danavorexton and OX-201 significantly increased the frequency of inspiratory synaptic currents of hypoglossal motoneurons. Danavorexton and OX-201 also showed significant effect and tendency, respectively, in increasing the frequency of burst activity recorded from the cervical (C3-C5) ventral root, which contains axons of phrenic motoneurons, in in vitro electrophysiologic analyses from rat isolated brainstem-spinal cord preparations. Electromyogram recordings revealed that intravenous administration of OX-201 increased burst frequency of the diaphragm and burst amplitude of the genioglossus muscle in isoflurane- and urethane-anesthetized rats, respectively. In whole-body plethysmography analyses, oral administration of OX-201 increased respiratory activity in free-moving mice. Overall, these results suggest that OX2R-selective agonists enhance respiratory function via activation of the diaphragm and genioglossus muscle through stimulation of inspiratory neurons in the pre-Bötzinger complex, and phrenic and hypoglossal motoneurons. OX2R-selective agonists could be promising drugs for various conditions with respiratory dysfunction.
Topics: Animals; Diaphragm; Motor Neurons; Orexin Receptors; Rats; Phrenic Nerve; Mice; Male; Hypoglossal Nerve; Rats, Sprague-Dawley; Inhalation; Medulla Oblongata; Isoquinolines; Pyridines
PubMed: 38917189
DOI: 10.1371/journal.pone.0306099 -
Drug Design, Development and Therapy 2024Nerve injury is a serious complication of percutaneous endoscopic transforaminal lumbar discectomy due to nerve root contact. The maximum tolerable concentration (MTC)...
Determining the Maximum Tolerable Concentration of Ropivacaine to Maintain Sensation of the Nerve Root in Percutaneous Endoscopic Transforaminal Lumbar Discectomy: Can Epidural Anaesthesia Achieve Pain-Tactile Separation Block to Avoid Nerve Injury?
INTRODUCTION
Nerve injury is a serious complication of percutaneous endoscopic transforaminal lumbar discectomy due to nerve root contact. The maximum tolerable concentration (MTC) of ropivacaine concentration for epidural anaesthesia, is defined as the concentration that minimises pain while preserving the sensation of the nerve roots. This distinct advantage allows the patient to provide feedback to the surgeon when the nerve roots are contacted.
METHODS
We used a biased-coin design to determine the MTC, which was estimated by the 10% effective concentration (EC), ie, the concentration at which 10% of patients lost sensation in the nerve roots. The determinant for positive response was lack of sensory feedback upon contact with the nerve root, and the feedback from occurrence of sensations in the innervation area upon contact with the nerve root was defined as a negative response. Primary outcome was the response from contact nerve root. Secondary outcomes were the type and number of statements of negative response and each patient's pain score during surgery.
RESULTS
Fifty-four patients were included in this study. The EC was 0.434% (95% CI: 0.410%, 0.440%) using isotonic regression in comparison with 0.431% (95% CI: 0.399%, 0.444%) using probit regression. Three type statements of negative response were reported including "tactile sensation", radiculalgia, and numbness.
CONCLUSION
The MTC of ropivacaine used for epidural anaesthesia was 0.434% to avoid nerve injury in percutaneous endoscopic transforaminal lumbar discectomy.
Topics: Ropivacaine; Humans; Male; Middle Aged; Female; Lumbar Vertebrae; Adult; Anesthetics, Local; Anesthesia, Epidural; Diskectomy, Percutaneous; Endoscopy; Spinal Nerve Roots; Dose-Response Relationship, Drug; Sensation; Aged
PubMed: 38915867
DOI: 10.2147/DDDT.S451980 -
BioRxiv : the Preprint Server For... Jun 2024Spinal cord stimulation (SCS) has emerged as a therapeutic tool for improving motor function following spinal cord injury. While many studies focus on restoring...
Spinal cord stimulation (SCS) has emerged as a therapeutic tool for improving motor function following spinal cord injury. While many studies focus on restoring locomotion, little attention is paid to enabling standing which is a prerequisite of walking. In this study, we fully characterize a new type of response to SCS, a long extension activated post-stimulation (LEAP). LEAP is primarily directed to ankle extensors and hence has great clinical potential to assist postural movements. To characterize this new response, we used the decerebrate cat model to avoid the suppressive effects of anesthesia, and combined EMG and force measurement in the hindlimb with intracellular recordings in the lumbar spinal cord. Stimulation was delivered as five-second trains via bipolar electrodes placed on the cord surface, and multiple combinations of stimulation locations (L4 to S2), amplitudes (50-600 uA), and frequencies (10-40 Hz) were tested. While the optimum stimulation location and frequency differed slightly among animals, the stimulation amplitude was key for controlling LEAP duration and amplitude. To study the mechanism of LEAP, we performed in vivo intracellular recordings of motoneurons. In 70% of motoneurons, LEAP increased at hyperpolarized membrane potentials indicating a synaptic origin. Furthermore, spinal interneurons exhibited changes in firing during LEAP, confirming the circuit origin of this behavior. Finally, to identify the type of afferents involved in generating LEAP, we used shorter stimulation pulses (more selective for proprioceptive afferents), as well as peripheral stimulation of the sural nerve (cutaneous afferents). The data indicates that LEAP primarily relies on proprioceptive afferents and has major differences from pain or withdrawal reflexes mediated by cutaneous afferents. Our study has thus identified and characterized a novel postural motor response to SCS which has the potential to expand the applications of SCS for patients with motor disorders.
PubMed: 38915687
DOI: 10.1101/2024.06.13.598885 -
Nature Communications Jun 2024Neuromuscular control of bionic arms has constantly improved over the past years, however, restoration of sensation remains elusive. Previous approaches to reestablish...
Neuromuscular control of bionic arms has constantly improved over the past years, however, restoration of sensation remains elusive. Previous approaches to reestablish sensory feedback include tactile, electrical, and peripheral nerve stimulation, however, they cannot recreate natural, intuitive sensations. Here, we establish an experimental biological sensorimotor interface and demonstrate its potential use in neuroprosthetics. We transfer a mixed nerve to a skeletal muscle combined with glabrous dermal skin transplantation, thus forming a bi-directional communication unit in a rat model. Morphological analyses indicate reinnervation of the skin, mechanoreceptors, NMJs, and muscle spindles. Furthermore, sequential retrograde labeling reveals specific sensory reinnervation at the level of the dorsal root ganglia. Electrophysiological recordings show reproducible afferent signals upon tactile stimulation and tendon manipulation. The results demonstrate the possibility of surgically creating an interface for both decoding efferent motor control, as well as encoding afferent tactile and proprioceptive feedback, and may indicate the way forward regarding clinical translation of biological communication pathways for neuroprosthetic applications.
Topics: Animals; Bionics; Rats; Muscle, Skeletal; Feedback, Sensory; Proprioception; Ganglia, Spinal; Mechanoreceptors; Muscle Spindles; Male; Female; Touch; Skin
PubMed: 38914540
DOI: 10.1038/s41467-024-49580-8 -
PloS One 2024Although a common injury there is a lack of published primary data to inform clinical management of sports related brachial plexus injuries. (Review)
Review
BACKGROUND
Although a common injury there is a lack of published primary data to inform clinical management of sports related brachial plexus injuries.
METHODS
A systematic search was completed in Medline, CINAHL, PubMed, SPORTDiscus and Web of Science databases and Google Scholar from inception to August 2023 according to the PRISMA-ScR guidelines. Methodological quality assessment of included articles was with the Joanna Briggs Institute tool. Studies providing primary data as to the rehabilitative management of diagnosed or suspected brachial plexus injuries sustained when playing contact sports were included.
RESULTS
Sixty-five studies were identified and screened, of which, 8 case reports were included, incorporating 10 participants with a mean age of 19.8 (±4.09) years. There was wide heterogeneity in injury severity, injury reporting, physical examination and imaging approaches documented. 9 of 10 participants returned to competitive sports, though follow-up periods also varied widely. Whilst return to play criteria varied between studies, the most consistent indicator was pain-free shoulder range of motion and strength.
CONCLUSIONS
There is a distinct lack of data available to inform evidence-based rehabilitation management of sports related brachial plexus injury. Only 8 individual case reports contain published data reporting on 10 athletes. Further reporting is critical to inform clinical management.
Topics: Humans; Brachial Plexus; Athletic Injuries; Young Adult; Male; Female; Range of Motion, Articular; Adult; Return to Sport; Brachial Plexus Neuropathies; Adolescent
PubMed: 38913647
DOI: 10.1371/journal.pone.0298317 -
JCI Insight May 2024Peripheral nerve injury-induced neuronal hyperactivity in the dorsal root ganglion (DRG) participates in neuropathic pain. The calcium-activated potassium channel...
Peripheral nerve injury-induced neuronal hyperactivity in the dorsal root ganglion (DRG) participates in neuropathic pain. The calcium-activated potassium channel subfamily N member 1 (KCNN1) mediates action potential afterhyperpolarization (AHP) and gates neuronal excitability. However, the specific contribution of DRG KCNN1 to neuropathic pain is not yet clear. We report that chronic constriction injury (CCI) of the unilateral sciatic nerve or unilateral ligation of the fourth lumbar nerve produced the downregulation of Kcnn1 mRNA and KCNN1 protein in the injured DRG. This downregulation was partially attributed to a decrease in DRG estrogen-related receptor gamma (ESRRG), a transcription factor, which led to reduced binding to the Kcnn1 promoter. Rescuing this downregulation prevented CCI-induced decreases in total potassium voltage currents and AHP currents, reduced excitability in the injured DRG neurons, and alleviated CCI-induced development and maintenance of nociceptive hypersensitivities, without affecting locomotor function and acute pain. Mimicking the CCI-induced DRG KCNN1 downregulation resulted in augmented responses to mechanical, heat, and cold stimuli in naive mice. Our findings indicate that ESRRG-controlled downregulation of DRG KCNN1 is likely essential for the development and maintenance of neuropathic pain. Thus, KCNN1 may serve as a potential target for managing this disorder.
Topics: Animals; Neuralgia; Ganglia, Spinal; Mice; Down-Regulation; Sensory Receptor Cells; Male; Peripheral Nerve Injuries; Mice, Inbred C57BL; Sciatic Nerve; Disease Models, Animal; Intermediate-Conductance Calcium-Activated Potassium Channels; Action Potentials
PubMed: 38912580
DOI: 10.1172/jci.insight.180085 -
Journal of Biomedical Optics Jul 2024Information about the spatial organization of fibers within a nerve is crucial to our understanding of nerve anatomy and its response to neuromodulation therapies. A...
NerveTracker: a Python-based software toolkit for visualizing and tracking groups of nerve fibers in serial block-face microscopy with ultraviolet surface excitation images.
SIGNIFICANCE
Information about the spatial organization of fibers within a nerve is crucial to our understanding of nerve anatomy and its response to neuromodulation therapies. A serial block-face microscopy method [three-dimensional microscopy with ultraviolet surface excitation (3D-MUSE)] has been developed to image nerves over extended depths . To routinely visualize and track nerve fibers in these datasets, a dedicated and customizable software tool is required.
AIM
Our objective was to develop custom software that includes image processing and visualization methods to perform microscopic tractography along the length of a peripheral nerve sample.
APPROACH
We modified common computer vision algorithms (optic flow and structure tensor) to track groups of peripheral nerve fibers along the length of the nerve. Interactive streamline visualization and manual editing tools are provided. Optionally, deep learning segmentation of fascicles (fiber bundles) can be applied to constrain the tracts from inadvertently crossing into the epineurium. As an example, we performed tractography on vagus and tibial nerve datasets and assessed accuracy by comparing the resulting nerve tracts with segmentations of fascicles as they split and merge with each other in the nerve sample stack.
RESULTS
We found that a normalized Dice overlap ( ) metric had a mean value above 0.75 across several millimeters along the nerve. We also found that the tractograms were robust to changes in certain image properties (e.g., downsampling in-plane and out-of-plane), which resulted in only a 2% to 9% change to the mean values. In a vagus nerve sample, tractography allowed us to readily identify that subsets of fibers from four distinct fascicles merge into a single fascicle as we move along the nerve's length.
CONCLUSIONS
Overall, we demonstrated the feasibility of performing automated microscopic tractography on 3D-MUSE datasets of peripheral nerves. The software should be applicable to other imaging approaches. The code is available at https://github.com/ckolluru/NerveTracker.
Topics: Software; Nerve Fibers; Imaging, Three-Dimensional; Algorithms; Animals; Image Processing, Computer-Assisted; Tibial Nerve; Vagus Nerve; Microscopy, Ultraviolet; Microscopy
PubMed: 38912214
DOI: 10.1117/1.JBO.29.7.076501 -
Cureus Jun 2024Background Postpartum peripheral nerve injuries can impact recovery. Elastic stockings are recommended for thromboembolism prevention, although concerns about entrapment...
Background Postpartum peripheral nerve injuries can impact recovery. Elastic stockings are recommended for thromboembolism prevention, although concerns about entrapment neuropathy exist. In this prospective observational study, we investigated the differential compressions caused by wearing elastic stockings before and after anesthesia, as well as changes in the diameters of the lower leg and ankle in parturient women undergoing spinal anesthesia for elective cesarean section (CS). Methods Eighteen pregnant women, classified by the American Society of Anesthesiologists as having physical status 2, underwent lower leg measurements taken before a CS. Elastic stockings were applied, and compression pressure was measured at pre-anesthesia, post-surgery, and six hours post-return to a hospital room. Fluid, blood loss, urine output, and neuropathy presence were recorded. For all parameters, changes at the three time points were compared for the primary analysis. For secondary analysis, participants were categorized as having intraoperative blood loss greater than (group P) or less than 1,000 g (group N), and factors were compared with pre-anesthesia and six hours post-return to a room. Data were analyzed and presented using a one-way analysis of variance with Bonferroni correction for multiple comparisons or unpaired two-tailed t-tests for pairwise comparison. Results None of the women had postoperative entrapment neuropathy. Six patients had >1,000 g of blood loss. Compression significantly increased from pre-anesthesia (left 13.6 ± 2.4, 95% CI: 12.18 to 14.52; right 13.4 ± 2.4, 95% CI: 12.41 to 14.69) to post-surgery (left, 17.4 ± 2.6, 95% CI: 15.68 to 18.12; right, 16.9 ± 2.6, 95% CI: 16.20 to 18.70) (p < 0.01). Compression pressure at post-surgery differed significantly between group P (left, 15.3 ± 1.3; right, 14.7 ± 1.8; 95% CI: -4.98 to -0.32) and group N (left, 18.1 ± 2.9; right, 17.8 ± 2.4; 95% CI: -5.38 to -0.26) (p < 0.05). The results are expressed as mean ± standard deviation, with P-values <0.05 indicating statistical significance. Conclusions In this study, no neuropathy occurred; however, over-compression risk with elastic stockings, especially when exceeding recommended pressure levels, was highlighted. Balancing thromboembolism prevention and over-compression risks is crucial for patients undergoing CSs with spinal anesthesia.
PubMed: 38912079
DOI: 10.7759/cureus.62809 -
ENeurologicalSci Jun 2024Intractable hiccups, persisting beyond 48 h, pose a clinical challenge, particularly in demyelinating diseases like Neuromyelitis Optica (NMO) and Multiple Sclerosis...
BACKGROUND
Intractable hiccups, persisting beyond 48 h, pose a clinical challenge, particularly in demyelinating diseases like Neuromyelitis Optica (NMO) and Multiple Sclerosis (MS). Understanding the complex neural pathways of the hiccup reflex and the impact of high-dose steroid therapy is crucial for managing this rare but distressing symptom. The hiccup reflex involves afferents from the vagus, phrenic, and sympathetic nerves, with the reflex center in the anterior horns at the C3 to 5 level and the medulla oblongata. The potential interplay between demyelination and corticosteroid therapy in triggering persistent hiccups requires exploration.
CASE REPORT
This case report details a 21-year-old male with undiagnosed demyelinating disorder, presenting persistent hiccups following high-dose steroid therapy for an acute disease flare. The patient's history included vertigo and progressive neurological symptoms, leading to an MS diagnosis with significant brain and spinal lesions. Persistent hiccups, initiated by steroid administration, were recurrent but responsive to metoclopramide after other measures failed.
DISCUSSION
The discussion centers on investigating the cause of hiccups in a patient with demyelination following steroid administration. Steroids' impact on neurological systems, including neurotransmitter function, and the potential disruption of neurological pathways due to demyelination may contribute to hiccups. Successful hiccup resolution with metoclopramide suggests a potential pharmacological approach for corticosteroid-induced hiccups in demyelinating diseases. This case emphasizes the need for further research into the intricate relationship between demyelination, steroid therapy, and hiccups to enhance management strategies for this uncommon yet impactful symptom.
PubMed: 38911508
DOI: 10.1016/j.ensci.2024.100509 -
Wellcome Open Research 2023Schwannoma is a nerve sheath tumour arising from differentiated Schwann cells, and melanocytic schwannoma (MS) is a rare variant where the Schwan cells produce melanin...
Schwannoma is a nerve sheath tumour arising from differentiated Schwann cells, and melanocytic schwannoma (MS) is a rare variant where the Schwan cells produce melanin pigment. MS is typically associated with spinal nerve roots and there have been only ~20 reports of cutaneous or subcutaneous MS to-date in humans. In canines, there have only been two reports of MS, both associated with spinal root nerves. In this report, we describe a 7-year-old Weimaraner cross breed dog that presented with two pigmented lesions on the eyelids. The lesions were surgically removed and histological analysis revealed well-circumscribed, non-encapsulated, expansile, neoplasms that were displacing most of the dermis and adnexa. The first lesion was composed of spindloid cells arranged in short interlacing streams with large amounts of pale eosinophilic cytoplasm that sometimes contained fine melanin granules. In areas there were spindle cells arranged in verocay bodies which led to a diagnosis of MS. In contrast, the second lesion was composed of polygonal cells arranged in thick sheets with large amounts of pale eosinophilic cytoplasm that sometimes contained fine melanin granules. The diagnosis was melanocytoma (which is one of the macroscopic differential diagnoses for MS). Whilst melanocytoma is a commonly occurring cutaneous lesion in canines and surgical removal is considered curative, due to little being known about MS in dogs, the outcome remained guarded, as MS in humans has an unpredictable nature, and recurrence and metastasis have been reported.
PubMed: 38911282
DOI: 10.12688/wellcomeopenres.19694.2