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Advanced Healthcare Materials Mar 2024Structural and functional healing of peripheral nerves damaged by trauma or chronic disease remain major clinical challenges, requiring the development of an effective...
Structural and functional healing of peripheral nerves damaged by trauma or chronic disease remain major clinical challenges, requiring the development of an effective nerve guidance conduit (NGC). The present study investigates a NGC fabrication strategy based on bredigite (BRT, CaMgSiO) bioceramic for the treatment of peripheral nerve injury. Here, BRT bioceramic shows good biocompatibility and sustainable release of Ca, Mg, and Si ions. Both BRT extracts and BRT-incorporating electrospun membranes promote the proliferation and myelination potential of RSC96 cells, as well as accelerate vascular formation by human umbilical vein endothelial cells. Notably, BRT facilitates RAW 264.7 cell polarization to the pro-healing phenotype under LPS-induced inflammatory stimulation. More importantly, the macrophages activated by BRT in turn promote RSC96 cell migration and remyelination. In a rat sciatic nerve defect model, improved electrophysiological performance and alleviated gastrocnemius muscle atrophy are observed at 12 weeks post-implantation. Further experiments verify that BRT-loaded NGC facilitates axonal regrowth and revascularization with high M2-like macrophage infiltration. These findings support the beneficial effects of BRT for creating a pro-healing immune microenvironment and orchestrating multicellular processes associated with functional nerve regeneration, indicating the potential of rationally engineered bioceramics as safe, effective, and economical materials for peripheral nerve repair.
Topics: Rats; Humans; Animals; Rats, Sprague-Dawley; Endothelial Cells; Sciatic Nerve; Nerve Regeneration; Macrophages; Asbestos, Amphibole
PubMed: 37972314
DOI: 10.1002/adhm.202302994 -
Anesthesiology Dec 2023Continuous nerve block with ropivacaine is commonly performed after repair surgery for traumatic peripheral nerve injuries. After peripheral nerve injury,...
BACKGROUND
Continuous nerve block with ropivacaine is commonly performed after repair surgery for traumatic peripheral nerve injuries. After peripheral nerve injury, tetrodotoxin-resistant voltage-gated sodium channel Nav1.8 is upregulated and contributes to macrophage inflammation. This study investigated whether ropivacaine promotes peripheral nerve regeneration through Nav1.8-mediated macrophage signaling.
METHODS
A sciatic nerve transection-repair (SNT) model was established in adult Sprague-Dawley rats of both sexes. The rats received 0.2% ropivacaine or 10 μM Nav1.8-selective inhibitor A-803467 around the injured site or near the sacrum for 3 days. Nerve regeneration was evaluated using behavioral, electrophysiologic, and morphological examinations. Moreover, myelin debris removal, macrophage phenotype, Nav1.8 expression, and neuropeptide expression were assessed using immunostaining, enzyme-linked immunosorbent assay, and Western blotting.
RESULTS
Compared to the SNT-plus-vehicle group, the sensory, motor, and sensory-motor coordination functions of the two ropivacaine groups were significantly improved. Electrophysiologic (mean ± SD: recovery index of amplitude, vehicle 0.43 ± 0.17 vs. ropivacaine 0.83 ± 0.25, n = 11, P < 0.001) and histological analysis collectively indicated that ropivacaine significantly promoted axonal regrowth (percentage of neurofilament 200 [NF-200]-positive area: vehicle 19.88 ± 2.81 vs. ropivacaine 31.07 ± 2.62, n = 6, P < 0.001). The authors also found that, compared to the SNT-plus-vehicle group, the SNT-plus-ropivacaine group showed faster clearance of myelin debris, accompanied by significantly increased macrophage infiltration and transition from the M1 to M2 phenotype. Moreover, ropivacaine significantly attenuated Nav1.8 upregulation at 9 days after sciatic nerve transection (vehicle 4.12 ± 0.30-fold vs. ropivacaine 2.75 ± 0.36-fold, n = 5, P < 0.001), which coincided with the increased expression of chemokine ligand 2 and substance P. Similar changes were observed when using the selective Nav1.8 channel inhibitor A-803467.
CONCLUSIONS
Continuous nerve block with ropivacaine promotes the structural and functional recovery of injured sciatic nerves, possibly by regulating Nav1.8-mediated macrophage signaling.
Topics: Male; Female; Rats; Animals; Ropivacaine; Rats, Sprague-Dawley; Peripheral Nerve Injuries; Axons; Nerve Regeneration; Sciatic Nerve; Macrophages
PubMed: 37669448
DOI: 10.1097/ALN.0000000000004761 -
International Journal of Molecular... Feb 2024Oxygen is compulsory for mitochondrial function and energy supply, but it has numerous more nuanced roles. The different roles of oxygen in peripheral nerve regeneration... (Review)
Review
Oxygen is compulsory for mitochondrial function and energy supply, but it has numerous more nuanced roles. The different roles of oxygen in peripheral nerve regeneration range from energy supply, inflammation, phagocytosis, and oxidative cell destruction in the context of reperfusion injury to crucial redox signaling cascades that are necessary for effective axonal outgrowth. A fine balance between reactive oxygen species production and antioxidant activity draws the line between physiological and pathological nerve regeneration. There is compelling evidence that redox signaling mediated by the Nox family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases plays an important role in peripheral nerve regeneration. Further research is needed to better characterize the role of Nox in physiological and pathological circumstances, but the available data suggest that the modulation of Nox activity fosters great therapeutic potential. One of the promising approaches to enhance nerve regeneration by modulating the redox environment is hyperbaric oxygen therapy. In this review, we highlight the influence of various oxygenation states, i.e., hypoxia, physoxia, and hyperoxia, on peripheral nerve repair and regeneration. We summarize the currently available data and knowledge on the effectiveness of using hyperbaric oxygen therapy to treat nerve injuries and discuss future directions.
Topics: Humans; Oxygen; Hyperoxia; Reactive Oxygen Species; NADPH Oxidases; Hypoxia; Peripheral Nerves; Nerve Regeneration
PubMed: 38396709
DOI: 10.3390/ijms25042030 -
International Journal of Biological... Dec 2023The incidence of peripheral nerve injury (PNI) is high worldwide, and a poor prognosis is common. Surgical closure and repair of the affected area are crucial to ensure...
The incidence of peripheral nerve injury (PNI) is high worldwide, and a poor prognosis is common. Surgical closure and repair of the affected area are crucial to ensure the effective treatment of peripheral nerve injuries. Despite being the standard treatment approach, reliance on sutures to seal the severed nerve ends introduces several limitations and restrictions. This technique is intricate and time-consuming, and the application of threading and punctate sutures may lead to tissue damage and heightened tension concentrations, thus increasing the risk of fixation failure and local inflammation. This study aimed to develop easily implantable chitosan-based peripheral nerve repair conduits that combine acrylic acid and cleavable N-hydroxysuccinimide to reduce nerve damage during repair. In ex vivo tissue adhesion tests, the conduit achieved maximal interfacial toughness of 705 J m ± 30 J m, allowing continuous bridging of the severed nerve ends. Adhesive repair significantly reduces local inflammation caused by conventional sutures, and the positive charge of chitosan disrupts the bacterial cell wall and reduces implant-related infections. This promises to open new avenues for sutureless nerve repair and reliable medical implants.
Topics: Humans; Peripheral Nerve Injuries; Chitosan; Adhesives; Sutureless Surgical Procedures; Inflammation; Nerve Regeneration; Peripheral Nerves
PubMed: 37709238
DOI: 10.1016/j.ijbiomac.2023.126793 -
Advanced Materials (Deerfield Beach,... Aug 2023Trauma often results in peripheral nerve injuries (PNIs). These injuries are particularly challenging therapeutically because of variable nerve diameters, slow axonal...
Trauma often results in peripheral nerve injuries (PNIs). These injuries are particularly challenging therapeutically because of variable nerve diameters, slow axonal regeneration, infection of severed ends, fragility of the nerve tissue, and the intricacy of surgical intervention. Surgical suturing is likely to cause additional damage to peripheral nerves. Therefore, an ideal nerve scaffold should possess good biocompatibility, diameter adaptability, and a stable biological interface for seamless biointegration with tissues. Inspired by the curl of Mimosa pudica, this study aimed to design and develop a diameter-adaptable, suture-free, stimulated curling bioadhesive tape (SCT) hydrogel for repairing PNI. The hydrogel is fabricated from chitosan and acrylic acid-N-hydroxysuccinimide lipid via gradient crosslinking using glutaraldehyde. It closely matches the nerves of different individuals and regions, thereby providing a bionic scaffold for axonal regeneration. In addition, this hydrogel rapidly absorbs tissue fluid from the nerve surface achieving durable wet-interface adhesion. Furthermore, the chitosan-based SCT hydrogel loaded with insulin-like growth factor-I effectively promotes peripheral nerve regeneration with excellent bioactivity. This procedure for peripheral nerve injury repair using the SCT hydrogel is simple and reduces the difficulty and duration of surgery, thereby advancing adaptive biointerfaces and reliable materials for nerve repair.
Topics: Rats; Animals; Humans; Tissue Scaffolds; Chitosan; Rats, Sprague-Dawley; Peripheral Nerves; Peripheral Nerve Injuries; Hydrogels; Nerve Regeneration; Sciatic Nerve
PubMed: 37205796
DOI: 10.1002/adma.202212015 -
Canadian Journal of Surgery. Journal... 2024Understanding patterns of peripheral nerve injuries (PNIs) and brachial plexus injuries (BPIs) is essential to preventing and appropriately managing nerve injuries. We...
BACKGROUND
Understanding patterns of peripheral nerve injuries (PNIs) and brachial plexus injuries (BPIs) is essential to preventing and appropriately managing nerve injuries. We sought to assess the incidence, cause, and severity of PNIs and BPIs sustained by patients with trauma.
METHODS
We conducted a retrospective review of the Trauma Registry Database (January 2002 to December 2020) to identify patients with PNIs or BPIs.
RESULTS
We evaluated data from 24 905 patients with trauma; 335 (1.3%) sustained PNIs (81% male; mean age 36 yr, standard deviation [SD] 16 yr) and 64 (0.3%) sustained BPIs (84% male; mean age 35, SD 15 yr). Nerves in the upper extremities were more commonly affected than those in the lower extremities. Sharp injuries (39.4%) and motorcycle accidents (32.8%) were the most frequent causes of PNIs and BPIs, respectively. Other common causes of PNI were motor vehicle collisions (16.7%) and gunshot wounds (12.8%). Many patients with PNIs (69.0%) and BPIs (53%) underwent operative management. The most frequent reconstruction for PNI was primary nerve repair (66%), while nerve transfers (48%) were more frequently used for BPI.
CONCLUSION
Nerve injuries in the trauma population have decreased over the last 3 decades with shifts in mechanisms of injury and use of imaging, electrodiagnostic tests, and surgery. Nerve injuries are often complex and time-sensitive to treat; understanding changes in trends is important to ensure optimal patient management.
Topics: Humans; Male; Adult; Peripheral Nerve Injuries; Female; Retrospective Studies; Brachial Plexus; Middle Aged; Incidence; Young Adult; Registries; Accidents, Traffic; Adolescent
PubMed: 38925857
DOI: 10.1503/cjs.002424 -
Nature Methods Nov 2023We develop soft and stretchable fatigue-resistant hydrogel optical fibers that enable optogenetic modulation of peripheral nerves in naturally behaving animals during...
We develop soft and stretchable fatigue-resistant hydrogel optical fibers that enable optogenetic modulation of peripheral nerves in naturally behaving animals during persistent locomotion. The formation of polymeric nanocrystalline domains within the hydrogels yields fibers with low optical losses of 1.07 dB cm, Young's modulus of 1.6 MPa, stretchability of 200% and fatigue strength of 1.4 MPa against 30,000 stretch cycles. The hydrogel fibers permitted light delivery to the sciatic nerve, optogenetically activating hindlimb muscles in Thy1::ChR2 mice during 6-week voluntary wheel running assays while experiencing repeated deformation. The fibers additionally enabled optical inhibition of pain hypersensitivity in an inflammatory model in TRPV1::NpHR mice over an 8-week period. Our hydrogel fibers offer a motion-adaptable and robust solution to peripheral nerve optogenetics, facilitating the investigation of somatosensation.
Topics: Mice; Animals; Optical Fibers; Optogenetics; Hydrogels; Motor Activity; Sciatic Nerve; Locomotion
PubMed: 37857906
DOI: 10.1038/s41592-023-02020-9 -
Zhonghua Yi Xue Za Zhi Jul 2023To investigate the clinical and neuroelectrophysiological characteristics of patients with primary peripheral nerve hyperexcitability syndrome (PNHS). The clinical...
To investigate the clinical and neuroelectrophysiological characteristics of patients with primary peripheral nerve hyperexcitability syndrome (PNHS). The clinical data of 20 patients who were diagnosed with PNHS in Beijing Tiantan Hospital from April 2016 to January 2023 were retrospectively collected. All patients underwent neuroelectrophysiological examinations. Clinical and electrophysiological characteristics were compared between the antibody positive and antibody negative groups, according to serum and cerebrospinal fluid anti-contactin-associated protein-like 2 (CASPR2) and/or anti-leucine-rich glioma-inactivated protein 1 (LGI-1) antibodies. There were 12 males and 8 females, with a mean age of (44.0±17.2) years and the disease course of [ (, )] 2.3 (1.1, 11.5) months. Motor symptoms included fasciculations, myokymia, muscle pain, cramps, and stiffness. These symptoms were commonly seen in the lower limbs (17 patients), followed by upper limbs (11 patients), face (11 patients) and trunk (9 patients). Nineteen (19/20) patients had sensory abnormalities and/or autonomic dysfunction, 13 patients had central nervous system involvement, and 5 patients had concomitant lung cancer or thymic lesions. The characteristic spontaneous potentials on needle electromyography (EMG) were myokymia potential (19 patients), fasciculation potential (12 patients), spastic potential (3 patients), neuromyotonic potential (1 patients), etc, which were commonly seen in the lower limb muscles, especially the gastrocnemius muscle(12 patients). After-discharge potential was found in 8 patients, and 7 were in the tibial nerve. Seven patients had positive serum anti-CASPR2 antibodies, and 3 of them had concomitant anti-LGI1 antibodies. And 1 patient had positive serum anti-LGI1 antibody alone. Compared with patients in the antibody negative group (=12), the patients who had anti-VGKC complex antibodies (=8) had a shorter course of disease [ (, ): 1.8 (1, 2) months vs 9.5 (3.3, 20.3) months, =0.012], higher incidence of after-discharge potential (6/8 vs 2/12, =0.019). The immunotherapy regimen (multi-dru, single-drug, no immunotherapy: 6, 2, 0 patients) in antibody-positive patients was different from the antibody-negative group (3, 6, 3 patients, =21.00, =0.023). The symptoms of motor nerve hyperexcitation, characteristic EMG spontaneous potentials and after-discharge potentials in PNHS patients are most commonly seen in the lower limbs. Attention should be paid to concomitant sensory and autonomic nerve hyperexcitation. PNHS patients with positive serum anti-CASPR2 antibodies may require immunotherapy with multiple drugs.
Topics: Male; Female; Humans; Adult; Middle Aged; Intracellular Signaling Peptides and Proteins; Retrospective Studies; Myokymia; Autoantibodies; Fasciculation; Peripheral Nerves
PubMed: 37402674
DOI: 10.3760/cma.j.cn112137-20230303-00320 -
Journal of Materials Chemistry. B Dec 2023Low efficiency of nerve growth and unstable release of loaded drugs have become a major problem in repairing peripheral nerve injury. Many intervention strategies were...
An extracellular matrix mimicking alginate hydrogel scaffold manipulates an inflammatory microenvironment and improves peripheral nerve regeneration by controlled melatonin release.
Low efficiency of nerve growth and unstable release of loaded drugs have become a major problem in repairing peripheral nerve injury. Many intervention strategies were focused on simple drug loading, but have still been less effective. The key challenge is to establish a controlled release microenvironment to enable adequate nerve regeneration. In this study, we fabricate a multilayered compound nerve scaffold by electrospinning: with an anti-adhesive outer layer of polycaprolactone and an ECM-like inner layer consisting of a melatonin-loaded alginate hydrogel. We characterized the scaffold, and the loaded melatonin can be found to undergo controlled release. We applied them to a 15 mm rat model of sciatic nerve injury. After 16 weeks, the animals in each group were evaluated and compared for recovery of motor function, electrophysiology, target organ atrophy status, regenerative nerve morphology and relative protein expression levels of neural markers, inflammatory oxidative stress, and angiogenesis. We identify that the scaffold can improve functional ability evidenced by an increased sciatic functional index and nerve electrical conduction level. The antioxidant melatonin loaded in the scaffold reduces inflammation and oxidative stress in the reinnervated nerves, confirmed by increased HO-1 and decreased TNF-α levels in regenerating nerves. The relative expression of fast-type myosin was elevated in the target gastrocnemius muscle. An improvement in angiogenesis facilitates neurite extension and axonal sprouting. This scaffold can effectively restore the ECM-like microenvironment and improve the quality of nerve regeneration by controlled melatonin release, thus enlightening the design criteria on nerve scaffolds for peripheral nerve injury in the future.
Topics: Rats; Animals; Melatonin; Hydrogels; Sciatic Nerve; Delayed-Action Preparations; Peripheral Nerve Injuries; Tissue Scaffolds; Nerve Regeneration; Extracellular Matrix
PubMed: 37982207
DOI: 10.1039/d3tb01727c -
Progress in Neurobiology Aug 2023Myelin improves axonal conduction velocity and is essential for nerve development and regeneration. In peripheral nerves, Schwann cells depend on bidirectional...
Myelin improves axonal conduction velocity and is essential for nerve development and regeneration. In peripheral nerves, Schwann cells depend on bidirectional mechanical and biochemical signaling to form the myelin sheath but the mechanism underlying this process is not understood. Rho GTPases are integrators of "outside-in" signaling that link cytoskeletal dynamics with cellular architecture to regulate morphology and adhesion. Using Schwann cell-specific gene inactivation in the mouse, we discovered that RhoA promotes the initiation of myelination, and is required to both drive and terminate myelin growth at different stages of peripheral myelination, suggesting developmentally-specific modes of action. In Schwann cells, RhoA targets actin filament turnover, via Cofilin 1, actomyosin contractility and cortical actin-membrane attachments. This mechanism couples actin cortex mechanics with the molecular organization of the cell boundary to target specific signaling networks that regulate axon-Schwann cell interaction/adhesion and myelin growth. This work shows that RhoA is a key component of a biomechanical response required to control Schwann cell state transitions for proper myelination of peripheral nerves.
Topics: Mice; Animals; Actins; Schwann Cells; Myelin Sheath; Peripheral Nerves; Axons
PubMed: 37315917
DOI: 10.1016/j.pneurobio.2023.102481