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Scientific Reports Jun 2022Understanding peripheral nerve micro-anatomy can assist in the development of safe and effective neuromodulation devices. However, current approaches for imaging nerve...
Understanding peripheral nerve micro-anatomy can assist in the development of safe and effective neuromodulation devices. However, current approaches for imaging nerve morphology at the fiber level are either cumbersome, require substantial instrumentation, have a limited volume of view, or are limited in resolution/contrast. We present alternative methods based on MUSE (Microscopy with Ultraviolet Surface Excitation) imaging to investigate peripheral nerve morphology, both in 2D and 3D. For 2D imaging, fixed samples are imaged on a conventional MUSE system either label free (via auto-fluorescence) or after staining with fluorescent dyes. This method provides a simple and rapid technique to visualize myelinated nerve fibers at specific locations along the length of the nerve and perform measurements of fiber morphology (e.g., axon diameter and g-ratio). For 3D imaging, a whole-mount staining and MUSE block-face imaging method is developed that can be used to characterize peripheral nerve micro-anatomy and improve the accuracy of computational models in neuromodulation. Images of rat sciatic and human cadaver tibial nerves are presented, illustrating the applicability of the method in different preclinical models.
Topics: Alprostadil; Animals; Axons; Imaging, Three-Dimensional; Nerve Fibers, Myelinated; Peripheral Nerves; Rats; Sciatic Nerve
PubMed: 35715554
DOI: 10.1038/s41598-022-14166-1 -
Muscle & Nerve Apr 2020Peripheral nerve injury remains a major cause of morbidity in trauma patients. Despite advances in microsurgical techniques and improved understanding of nerve... (Review)
Review
Peripheral nerve injury remains a major cause of morbidity in trauma patients. Despite advances in microsurgical techniques and improved understanding of nerve regeneration, obtaining satisfactory outcomes after peripheral nerve injury remains a difficult clinical problem. There is a growing body of evidence in preclinical animal studies demonstrating the supportive role of stem cells in peripheral nerve regeneration after injury. The characteristics of both mesoderm-derived and ectoderm-derived stem cell types and their role in peripheral nerve regeneration are discussed, specifically focusing on the presentation of both foundational laboratory studies and translational applications. The current state of clinical translation is presented, with an emphasis on both ethical considerations of using stems cells in humans and current governmental regulatory policies. Current advancements in cell-based therapies represent a promising future with regard to supporting nerve regeneration and achieving significant functional recovery after debilitating nerve injuries.
Topics: Humans; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Recovery of Function; Stem Cell Transplantation
PubMed: 31725911
DOI: 10.1002/mus.26760 -
Cells, Tissues, Organs 2023Peripheral nerve injury results in loss of motor and sensory function distal to the nerve injury and is often permanent in nerve gaps longer than 5 cm. Autologous nerve...
Peripheral nerve injury results in loss of motor and sensory function distal to the nerve injury and is often permanent in nerve gaps longer than 5 cm. Autologous nerve grafts (nerve autografts) utilize patients' own nerve tissue from another part of their body to repair the defect and are the gold standard in care. However, there is a limited autologous tissue supply, size mismatch between donor nerve and injured nerve, and morbidity at the site of nerve donation. Decellularized cadaveric nerve tissue alleviates some of these limitations and has demonstrated success clinically. We previously developed an alternative apoptosis-assisted decellularization process for nerve tissue. This new process may result in an ideal scaffold for peripheral nerve regeneration by gently removing cells and antigens while preserving delicate topographical cues. In addition, the apoptosis-assisted process requires less active processing time and is inexpensive. This study examines the utility of apoptosis-decellularized peripheral nerve scaffolds compared to detergent-decellularized peripheral nerve scaffolds and isograft controls in a rat nerve gap model. Results indicate that, at 8 weeks post-injury, apoptosis-decellularized peripheral nerve scaffolds perform similarly to detergent-decellularized and isograft controls in both functional (muscle weight recovery, gait analysis) and histological measures (neurofilament staining, macrophage infiltration). These new apoptosis-decellularized scaffolds hold great promise to provide a less expensive scaffold for nerve injury repair, with the potential to improve nerve regeneration and functional outcomes compared to current detergent-decellularized scaffolds.
Topics: Humans; Rats; Animals; Detergents; Peripheral Nerves; Nerve Tissue; Macrophages; Apoptosis; Nerve Regeneration; Tissue Scaffolds; Tissue Engineering; Sciatic Nerve
PubMed: 36030771
DOI: 10.1159/000525704 -
Anaesthesia Jan 2021The accuracy and reliability of ultrasound are still insufficient to guarantee complete and safe nerve block for all patients. Injection of local anaesthetic close to,... (Review)
Review
The accuracy and reliability of ultrasound are still insufficient to guarantee complete and safe nerve block for all patients. Injection of local anaesthetic close to, but not touching, the nerve is key to outcomes, but the exact relationship between the needle tip and nerve epineurium is difficult to evaluate, even with ultrasound. Ultrasound has insufficient resolution, tissues are difficult to discern due to acoustic impedance and needles are more difficult to see with increased angulation. The limitations of ultrasound have shifted the focus of innovation towards bio-markers that help detect needle tip position by utilising the physical properties of tissues, (e.g. pressure, electrical, optics, acoustic and elastic). Although most are at the laboratory stage and results are as yet only available from phantom or cadaver studies, clinical trials are imminent. For example, fine optical fibres placed within the lumen of block needles can measure needle tip pressure. Electrical impedance differentiates between intraneural and perineural needle tip placement. A new tip tracker needle has a piezo element embedded at its distal end that tracks the needle tip in-plane and out-of-plane as a blue/red or green circle depending on its relative location within the beam. Micro-ultrasound at the tip of the needle is in development. Early images using 40MHz in anaesthetised pigs reveal muscle striation, distinct epineurium and 30-40 fascicles > 75 micron in diameter. The next few years will see a technological revolution in tip-tracking technology that has the potential to improve patient safety and, in doing so, change practice.
Topics: Anesthetics, Local; Animals; Needles; Nerve Block; Peripheral Nerves; Ultrasonography, Interventional
PubMed: 33426657
DOI: 10.1111/anae.15232 -
International Journal of Nanomedicine 2022Peripheral nerve injury (PNI) is a worldwide problem which hugely affects the quality of patients' life. Nerve conduits are now the alternative for treatment of PNI to... (Review)
Review
Peripheral nerve injury (PNI) is a worldwide problem which hugely affects the quality of patients' life. Nerve conduits are now the alternative for treatment of PNI to mimic the gold standard, autologous nerve graft. In that case, with the advantages of electrospun micro- or nano-fibers nerve conduit, the peripheral nerve growth can be escalated, in a better way. In this systematic review, we focused on 39 preclinical studies of electrospun nerve conduit, which include the in vitro and in vivo evaluation from animal peripheral nerve defect models, to provide an update on the progress of the development of electrospun nerve conduit over the last 5 years (2016-2021). The physical characteristics, biocompatibility, functional and morphological outcomes of nerve conduits from different studies would be compared, to give a better strategy for treatment of PNI.
Topics: Animals; Peripheral Nerves; Prostheses and Implants; Nerve Regeneration; Sciatic Nerve; Tissue Scaffolds
PubMed: 36600878
DOI: 10.2147/IJN.S362144 -
Anesthesiology Nov 2020Two regional analgesic modalities currently cleared by the U.S. Food and Drug Administration hold promise to provide postoperative analgesia free of many of the... (Review)
Review
Two regional analgesic modalities currently cleared by the U.S. Food and Drug Administration hold promise to provide postoperative analgesia free of many of the limitations of both opioids and local anesthetic-based techniques. Cryoneurolysis uses exceptionally low temperature to reversibly ablate a peripheral nerve, resulting in temporary analgesia. Where applicable, it offers a unique option given its extended duration of action measured in weeks to months after a single application. Percutaneous peripheral nerve stimulation involves inserting an insulated lead through a needle to lie adjacent to a peripheral nerve. Analgesia is produced by introducing electrical current with an external pulse generator. It is a unique regional analgesic in that it does not induce sensory, motor, or proprioception deficits and is cleared for up to 60 days of use. However, both modalities have limited validation when applied to acute pain, and randomized, controlled trials are required to define both benefits and risks.
Topics: Acute Pain; Analgesia; Cryotherapy; Electric Stimulation Therapy; Humans; Pain Management; Peripheral Nerves
PubMed: 32898231
DOI: 10.1097/ALN.0000000000003532 -
Ulusal Travma Ve Acil Cerrahi Dergisi =... Aug 2022Delayed autologous nerve graft reconstruction is inevitable in devastating injuries. Delayed or prolonged repair time has deleterious effects on nerve grafts. We aimed...
BACKGROUND
Delayed autologous nerve graft reconstruction is inevitable in devastating injuries. Delayed or prolonged repair time has deleterious effects on nerve grafts. We aimed improving and accelerating nerve graft reconstruction process in a rat long nerve defect model with loop nerve graft prefabrication particularly to utilize for injuries with tissue loss.
METHODS
Twenty-four Sprague-Dawley rats were allocated into three groups. 1.5 cm long peroneal nerve segment was excised, reversed in orientation, and used as autologous nerve graft. In conventional interpositional nerve graft group (Group 1), nerve defects were repaired in single-stage. In loop nerve graft prefabrication group (Group 2), grafts were sutured end-to-end (ETE) to the proximal peroneal nerve stumps. Distal ends of the grafts were sutured end-to-side to the peroneal nerve stumps 5 mm proximal to the ETE repair sites in first stage. In second stage, distal ends of the prefabricated grafts were transposed and sutured to distal nerve stumps. In staged conventional interpositional nerve graft group (Group 3), grafts were sutured ETE to proximal peroneal nerve stumps in first stage. Distal ends of the grafts and nerve stumps were tacked to the surrounding muscles until the final repair in second stage. Follow-up period was 4 weeks for each stage in Groups 2 and 3, and 8 weeks for Group 1. Peroneal function index (PFI), electrophysiology, and histological assessments were conducted after 8 weeks. P<0.05 was considered significant for statistical analysis.
RESULTS
PFI results of Group 1 (-22.75±5.76) and 2 (-22.08±6) did not show statistical difference (p>0.05). Group 3 (-33.64±6.4) had a statistical difference compared to other groups (p<0.05). Electrophysiology results of Group 1 (16.19±2.15 mV/1.16±0.21 ms) and 2 (15.95±2.82 mV/1.17±0.16 ms) did not present statistical difference (p>0.05), whereas both groups had a statistical difference compared to Group 3 (10.44±1.96 mV/1.51±0.15 ms) (p<0.05). Axon counts of Group 1 (2227±260.4) and 3 (2194±201.1) did not have statistical difference (p>0.05), whereas both groups had significantly poor axon counts compared to Group 2 (2531±91.18) (p<0.05).
CONCLUSION
Loop nerve graft prefabrication improved axonal regeneration without delay. Loop prefabrication can accelerate prolonged regeneration time for the injuries indicating a delayed nerve reconstruction. Higher axon counts derived with loop nerve prefabrication may even foster its investigation in immediate long nerve defect reconstructions in further studies.
Topics: Animals; Nerve Regeneration; Neurosurgical Procedures; Peripheral Nerves; Peroneal Nerve; Rats; Rats, Sprague-Dawley; Sciatic Nerve
PubMed: 35920436
DOI: 10.14744/tjtes.2022.68353 -
Diabetologia Dec 2023Our aim was to investigate structural changes of cutaneous Schwann cells (SCs), including nociceptive Schwann cells (nSCs) and axons, in individuals with diabetic...
AIMS/HYPOTHESIS
Our aim was to investigate structural changes of cutaneous Schwann cells (SCs), including nociceptive Schwann cells (nSCs) and axons, in individuals with diabetic polyneuropathy. We also aimed to investigate the relationship between these changes and peripheral neuropathic symptoms in type 1 diabetes.
METHODS
Skin biopsies (3 mm) taken from carefully phenotyped participants with type 1 diabetes without polyneuropathy (T1D, n=25), type 1 diabetes with painless diabetic polyneuropathy (T1DPN, n=30) and type 1 diabetes with painful diabetic polyneuropathy (P-T1DPN, n=27), and from healthy control individuals (n=25) were immunostained with relevant antibodies to visualise SCs and nerve fibres. Stereological methods were used to quantify the expression of cutaneous SCs and nerve fibres.
RESULTS
There was a difference in the number density of nSCs not abutting to nerve fibres between the groups (p=0.004) but not in the number density of nSCs abutting to nerve fibres, nor in solitary or total subepidermal SC soma number density. The overall dermal SC expression (measured by dermal SC area fraction and subepidermal SC process density) and peripheral nerve fibre expression (measured by intraepidermal nerve fibre density, dermal nerve fibre area fraction and subepidermal nerve fibre density) differed between the groups (all p<0.05): significant differences were seen in participants with T1DPN and P-T1DPN compared with those without diabetic polyneuropathy (healthy control and T1D groups) (all p<0.05). No difference was found between participants in the T1DPN and P-T1DPN group, nor between participants in the T1D and healthy control group (all p>0.05). Correlational analysis showed that cutaneous SC processes and nerve fibres were highly associated, and they were weakly negatively correlated with different neuropathy measures.
CONCLUSIONS/INTERPRETATION
Cutaneous SC processes and nerves, but not SC soma, are degenerated and interdependent in individuals with diabetic polyneuropathy. However, an increase in structurally damaged nSCs was seen in individuals with diabetic polyneuropathy. Furthermore, dermal SC processes and nerve fibres correlate weakly with clinical measures of neuropathy and may play a partial role in the pathophysiology of diabetic polyneuropathy in type 1 diabetes.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus, Type 1; Nerve Fibers; Peripheral Nerves; Schwann Cells
PubMed: 37728731
DOI: 10.1007/s00125-023-06009-z -
British Journal of Hospital Medicine... Oct 2022Peripheral regional blockade is a type of regional anaesthesia involving depositing local anaesthetics around a specific nerve or bundle of nerves that help transmit... (Review)
Review
Peripheral regional blockade is a type of regional anaesthesia involving depositing local anaesthetics around a specific nerve or bundle of nerves that help transmit nociceptive signals to higher centres, such as the thalamus and somatosensory cortex. It is not only a widely used technique that provides surgical anaesthesia, but also acts as an essential part of the armamentarium against postoperative pain and pain following major skeletal trauma. This article discusses the structure and function of peripheral nerves, the classification and pathophysiology of peripheral nerve injury and, finally, how practising anaesthetists are committed to maximising success and minimising harm when performing peripheral nerve blockade in the operating theatre.
Topics: Humans; Nerve Block; Anesthesia, Conduction; Anesthetics, Local; Pain, Postoperative; Anesthesia, Local; Peripheral Nerves
PubMed: 36322433
DOI: 10.12968/hmed.2022.0304 -
Acta Bio-medica : Atenei Parmensis Apr 2021Muscle in vein (MIV ) conduits have gradually been employed in the last 20 years as a valuable technique in bridging peripheral nerve gaps after nerve lesions who cannot...
Muscle in vein (MIV ) conduits have gradually been employed in the last 20 years as a valuable technique in bridging peripheral nerve gaps after nerve lesions who cannot undergo a direct tension-free coaptation. The advantages of this procedure comparing to the actual benchmark (autograft) is the sparing of the donor site, and the huge availability of both components (i.e. muscle and veins). Here we present a case serie of four MIV performed at our hospital from 2018 to 2019. The results we obtained in our experi-ence confirmed its effectiveness both in nerve regeneration (as sensibility recovery) and in neuropathic pain eradication. Our positive outcomes encourage its use in selected cases of residual nerve gaps up to 30 mm.
Topics: Humans; Muscles; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Veins
PubMed: 33944845
DOI: 10.23750/abm.v92iS1.9202