Transgenic Schwann cells overexpressing POU6F1 promote sciatic nerve regeneration within acellular nerve allografts.

Objective.Acellular nerve allograft (ANA) is an effective surgical approach used to bridge the sciatic nerve gap. The molecular regulators of post-surgical recovery are not well-known. Here, we explored the effect of transgenic Schwann cells (SCs) overexpressing POU domain class 6, transcription factor 1 (POU6F1) on sciatic nerve regeneration within ANAs. We explored the functions of POU6F1 in nerve regeneration by using a cell model of H2O2-induced SCs injury and transplanting SCs overexpressing POU6F1 into ANA to repair sciatic nerve gaps.Approach.Using RNA-seq, Protein-Protein Interaction network analysis, gene ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway analysis, we identified a highly and differentially expressed transcription factor, POU6F1, following ANA treatment of sciatic nerve gap. Expressing a high degree of connectivity, POU6F1 was predicted to play a role in peripheral nervous system myelination.Main results.To test the role of POU6F1 in nerve regeneration after ANA, we infected SCs with adeno-associated virus-POU6F1, demonstrating that POU6F1 overexpression promotes proliferation, anti-apoptosis, and migration of SCsin vitro. We also found that POU6F1 significantly upregulated JNK1/2 and c-Jun phosphorylation and that selective JNK1/2 inhibition attenuated the effects of POU6F1 on proliferation, survival, migration, and JNK1/2 and c-Jun phosphorylation. The direct interaction of POU6F1 and activated JNK1/2 was subsequently confirmed by co-immunoprecipitation. In rat sciatic nerve injury model with a 10 mm gap, we confirmed the pattern of POU6F1 upregulation and co-localization with transplanted SCs. ANAs loaded with POU6F1-overexpressing SCs demonstrated the enhanced survival of transplanted SCs, axonal regeneration, myelination, and functional motor recovery compared to the ANA group loaded by SCs-only in line within vitrofindings.Significance.This study identifies POU6F1 as a novel regulator of post-injury sciatic nerve repair, acting through JNK/c-Jun signaling in SCs to optimize therapeutic outcomes in the ANA surgical approach.

Use of aerobic treadmill exercises on nerve regeneration after sciatic nerve injury in spontaneously hypertensive rats.

PURPOSE: Various postoperative protocols have been proposed to improve outcomes and accelerate nerve regeneration. Recently, the use of physical exercise in a post-surgical neurorraphy procedure has shown good results when started early. We experimentally investigated the hypothesis that post-operative exercise speeds up results and improves clinical and morphologic parameters. METHODS: Isogenic rats were randomly divided into four groups: 1 SHAM; 2 SHAM submitted to the exercise protocol (EP); 3 Grafting of the sciatic nerve; and 4 Grafting of the sciatic nerve associated with the EP. The EP was based on aerobic activities with a treadmill, with a progressive increase in time and intensity during 6 weeks. The results were evaluated by the sciatic functional index (SFI), morphometric and morphologic analysis of nerve distal to the lesion, and the number of spinal cord motor neurons, positive to the marker Fluoro-Gold (FG), captured retrogradely through neurorraphy. RESULTS: Functional analysis (SFI) did not show a statistical difference between the group grafted with (-50.94) and without exercise (-65.79) after 90 days. The motoneurons count (Spinal cord histology) also showed no diference between these groups (834.5 × 833 respectively). Although functionally there is no difference between these groups, morphometric study showed a greater density (53.62) and larger fibers (7.762) in GRAFT group. When comparing both operated groups with both SHAM groups, all values were much lower. CONCLUSIONS: The experimental model that this aerobic treadmill exercises protocol did not modify nerve regeneration after sciatic nerve injury and repair with nerve graft.

Open Sciatic Nerve Decompression for Compartment Syndrome after Prolonged Lithotomy Position: A Case Report.

Background: Position-related compressive nerve injury is a frequently reported complication of the lithotomy position. In contrast, compartment syndrome-induced neuropathy after lithotomy with prolonged surgery is rare and prone to misdiagnosis. This case describes the successful open decompression of sciatic neuropathy due to compartment syndrome after a prolonged lithotomy position. Case presentation: A 56-year-old male patient complained of an abnormal sensation in the lower leg and difficulty in dorsiflexion and plantarflexion of the left foot and toes after laparoscopic anterior hepatic sectionectomy for 16 h in a lithotomy position. Physical examination revealed severe pain and paresthesia below the distal left thigh. In manual muscle test grading, dorsiflexion and plantarflexion of the left ankle and toes were classified as grade 1. Computed tomography and magnetic resonance imaging showed ischemic changes in the mid-thigh posterior muscles, and the sciatic nerve was severely swollen at the distal thigh, which was compressed by the proximal edge of the well-leg holder. After debridement of the necrotic tissue and decompression of the sciatic nerve, the pain subsided immediately, and the ankle and toe dorsiflexion motor function improved to grade 4. Conclusions: Most case reports of compressive neuropathy associated with the lithotomy position have been related to conservative treatment. However, if a lesion compressing the nerve is confirmed in an imaging study and the correlation with the patient's symptoms is evident, early surgical intervention can be an effective treatment method to minimize neurological deficits.

Peripheral Blood Mononuclear Cells Regulate Differentially Expressed Proteins in the Proximal Sciatic Nerve of Rats after Transection Anastomosis.

Peripheral nerve injury (PNI) is a common disease that causes the partial loss of sensory, exercise, and autonomic nervous function. In clinical practice, accurate end-to-end neurorrhaphy of the epineurium without tension is the ideal treatment when there is no nerve defect. We have confirmed that peripheral blood mononuclear cells (PBMCs) can effectively improve nerve regeneration and motor function recovery after PNI. However, the global protein profile and signaling conduction pathways regulated by PBMCs remain unclear. This study employed the transection anastomosis model to detect the walking track analysis, gastrocnemius wet weight rate, and morphological examination in order to validate the effect of PBMCs on sciatic nerve injury in rats. Results showed that PBMCs improved nerve regeneration after sciatic nerve dissociation and anastomosis in rats, which reflected in the improvement of the sciatic nerve function index, wet weight rate of gastrocnemius muscles, muscle fiber structure, and the number of axons. We then used TMT labeling quantitative proteomics to explore the underlying mechanism by which PBMCs ameliorated sciatic nerve injury. Results showed that PBMCs regulated 40 differential proteins and the regulated proteins were primarily involved in the complement and coagulation cascade pathways, the notch signaling pathway, the renin angiotensin system, DNA replication, histidine metabolism, ß-alanine metabolism, and other types of O-glycan biosynthesis. Immunohistochemical results supported our findings on the changes in expression of Kininogen 1 and Psen1, the relationships between PNI and the notch pathway and the complement and coagulation level pathways.

"Floating Hip" and "Floating Knee" Associated with Hip Dislocation, Sciatic Nerve Palsy, and Patella Fracture: A Case Report.

CASE: We report a very rare case of simultaneous ipsilateral floating hip and floating knee (SIFHFK) injury with the neck of the femur and patella fracture and hip dislocation associated with sciatic nerve injury in a 45-year-old man after a road traffic accident. We adopted a staged approach for surgical fixation of the fractures after stabilization. At the latest 2 years follow-up, the patient was asymptomatic with satisfactory clinical outcome. CONCLUSION: SIFHFK injuries present a challenging and emergent clinical scenario and require extensive clinical experience, careful planning, and multidisciplinary teamwork because of the paucity of specific treatment protocols for the treatment of this complex injury.

Infección de heridas quirúrgicas en un paciente con neuropatía ciática: caso clínico / Surgical wound infection in a patient with sciatic neuropathy: a case report

La neuropatía ciática es una patología que se manifiesta en alteraciones mecánicas, funcionales y sensitivas de la extremidad afectada. Se presenta el caso de un paciente con neuropatía ciática iatrogénica que mostró evolución tórpida de las heridas quirúrgicas tras intervención de dedos en garra con inmovilización por agujas de Kirschner. Con un tratamiento basado en desbridamiento, cura húmeda y abordaje de la colonización crítica se consiguió alta en 45 días, con curas realizadas en domicilio por el paciente, y resolución completa en 60 días (AU)

Sciatic neuropathy is a pathology manifested in mechanical, functional and sensitive disorders in the affected limb. We report a case of iatrogenic sciatic neuropathy in a patient showing torpid evolution of postsurgical wounds after claw toes surgery with K-wire immobilization. Treatment was based in debridement, critical colonization contention and moist environment healing. The patient was released for self-treatment at home after 45 days and reported complete healing after 60 days (AU)

Functional Outcomes of Nerve Allografts Seeded with Undifferentiated and Differentiated Mesenchymal Stem Cells in a Rat Sciatic Nerve Defect Model.

BACKGROUND: Mesenchymal stem cells have the potential to produce neurotrophic growth factors and establish a supportive microenvironment for neural regeneration. The purpose of this study was to determine the effect of undifferentiated and differentiated mesenchymal stem cells dynamically seeded onto decellularized nerve allografts on functional outcomes when used in peripheral nerve repair. METHODS: In 80 Lewis rats, a 10-mm sciatic nerve defect was reconstructed with (1) autograft, (2) decellularized allograft, (3) decellularized allograft seeded with undifferentiated mesenchymal stem cells, or (4) decellularized allograft seeded with mesenchymal stem cells differentiated into Schwann cell-like cells. Nerve regeneration was evaluated over time by cross-sectional tibial muscle ultrasound measurements, and at 12 and 16 weeks by isometric tetanic force measurements, compound muscle action potentials, muscle mass, histology, and immunofluorescence analyses. RESULTS: At 12 weeks, undifferentiated mesenchymal stem cells significantly improved isometric tetanic force measurement and compound muscle action potential outcomes compared to decellularized allograft alone, whereas differentiated mesenchymal stem cells significantly improved compound muscle action potential outcomes. The autografts outperformed both stem cell groups histologically at 12 weeks. At 16 weeks, functional outcomes normalized between groups. At both time points, the effect of undifferentiated versus differentiated mesenchymal stem cells was not significantly different. CONCLUSIONS: Undifferentiated and differentiated mesenchymal stem cells significantly improved functional outcomes of decellularized allografts at 12 weeks and were similar to autograft results in the majority of measurements. At 16 weeks, outcomes normalized as expected. Although differences between both cell types were not statistically significant, undifferentiated mesenchymal stem cells improved functional outcomes of decellularized nerve allografts to a greater extent and had practical benefits for clinical translation by limiting preparation time and costs.

Administration of Purified Exosome Product in a Rat Sciatic Serve Reverse Autograft Model.

BACKGROUND: The nerve autograft remains the gold standard when reconstructing peripheral nerve defects. However, although autograft repair can result in useful functional recovery, poor outcomes are common, and better treatments are needed. The purpose of this study was to evaluate the effect of purified exosome product on functional motor recovery and nerve-related gene expression in a rat sciatic nerve reverse autograft model. METHODS: Ninety-six Sprague-Dawley rats were divided into three experimental groups. In each group, a unilateral 10-mm sciatic nerve defect was created. The excised nerve was reversed and used to reconstruct the defect. Group I animals received the reversed autograft alone, group II animals received the reversed autograft with fibrin glue, and group III animals received the reversed autograft with purified exosome product suspended in the fibrin glue. The animals were killed at 3 and 7 days and 12 and 16 weeks after surgery. Evaluation included compound muscle action potentials, isometric tetanic force, tibialis anterior muscle wet weight, nerve regeneration-related gene expression, and nerve histomorphometry. RESULTS: At 16 weeks, isometric tetanic force was significantly better in group III (p = 0.03). The average axon diameter of the peroneal nerve was significantly larger in group III at both 12 and 16 weeks (p = 0.015 at 12 weeks; p < 0.01 at 16 weeks). GAP43 and S100b gene expression was significantly up-regulated by purified exosome product. CONCLUSIONS: Local administration of purified exosome product demonstrated improved nerve regeneration profiles in the reverse sciatic nerve autograft rat model. Thus, purified exosome product may have beneficial effects on nerve regeneration, gene profiles, and motor outcomes.

Investigation of Neuropathology after Nerve Release in Chronic Constriction Injury of Rat Sciatic Nerve.

Peripheral compressive neuropathy causes significant neuropathic pain, muscle weakness and prolong neuroinflammation. Surgical decompression remains the gold standard of treatment but the outcome is suboptimal with a high recurrence rate. From mechanical compression to chemical propagation of the local inflammatory signals, little is known about the distinct neuropathologic patterns and the genetic signatures after nerve decompression. In this study, controllable mechanical constriction forces over rat sciatic nerve induces irreversible sensorimotor dysfunction with sustained local neuroinflammation, even 4 weeks after nerve release. Significant gene upregulations are found in the dorsal root ganglia, regarding inflammatory, proapoptotic and neuropathic pain signals. Genetic profiling of neuroinflammation at the local injured nerve reveals persistent upregulation of multiple genes involving oxysterol metabolism, neuronal apoptosis, and proliferation after nerve release. Further validation of the independent roles of each signal pathway will contribute to molecular therapies for compressive neuropathy in the future.

Efficacy of Silicone Conduit in the Rat Sciatic Nerve Repair Model: Journey of a Thousand Miles.

BACKGROUND: A lot of options have been tried for bridging the two ends of the injured nerves. Researchers have used decellularized nerve grafts, artificial materials and even nerve growth factors to augment functional recovery. These materials are either costly or inaccessible in developing world. OBJECTIVE: The study aimed to evaluate the efficacy of the silicone conduit in a rat sciatic nerve injury model. MATERIALS AND METHODS: 24 healthy Sprague-Dawley (SD) rats (250-300 grams; 8-10 weeks) were used and right sciatic nerve was exposed; transected and re-anastomosed by two different methods in 16 rats. In control group, n = 8 (Group I) the sciatic nerve was untouched; Group II (reverse nerve anastomosis, n = 8): 1-centimeter of nerve was cut and re-anastomosed by using 10-0 monofilament suture; Group III (silicone conduit, n = 8) 1-centimeter nerve segment was cut, replaced by silicone conduit and supplemented by fibrin glue]. Evaluation of nerve recovery was done functionally (pain threshold and sciatic functional index) over 3 months and histologically and electron microscopically. RESULTS: Functional results showed a trend of clinical improvement in Group III and II but recovery was poor and never reached up to normal. Histopathological and electron microscopic results showed an incomplete axonal regeneration in Groups II and III. Psychological analyses showed that no outwards signs of stress were present and none of the rats showed paw biting and teeth chattering. CONCLUSION: The silicone conduit graft may be an economical and effective alternative to presently available interposition grafts, however for short segments only.

Adipose tissue stem cells in peripheral nerve regeneration-In vitro and in vivo.

After peripheral nerve injury, Schwann cells (SCs) are crucially involved in several steps of the subsequent regenerative processes, such as the Wallerian degeneration. They promote lysis and phagocytosis of myelin, secrete numbers of neurotrophic factors and cytokines, and recruit macrophages for a biological debridement. However, nerve injuries with a defect size of >1 cm do not show proper tissue regeneration and require a surgical nerve gap reconstruction. To find a sufficient alternative to the current gold standard-the autologous nerve transplant-several cell-based therapies have been developed and were experimentally investigated. One approach aims on the use of adipose tissue stem cells (ASCs). These are multipotent mesenchymal stromal cells that can differentiate into multiple phenotypes along the mesodermal lineage, such as osteoblasts, chondrocytes, and myocytes. Furthermore, ASCs also possess neurotrophic features, that is, they secrete neurotrophic factors like the nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, ciliary neurotrophic factor, glial cell-derived neurotrophic factor, and artemin. They can also differentiate into the so-called Schwann cell-like cells (SCLCs). These cells share features with naturally occurring SCs, as they also promote nerve regeneration in the periphery. This review gives a comprehensive overview of the use of ASCs in peripheral nerve regeneration and peripheral nerve tissue engineering both in vitro and in vivo. While the sustainability of differentiation of ASCs to SCLCs in vivo is still questionable, ASCs used with different nerve conduits, such as hydrogels or silk fibers, have been shown to promote nerve regeneration.

[Treatment of sciatic posttraumatic neuropathy with chronic neuromodulation and endoscopic technics]. / Lechenie posttravmaticheskoi nevropatii sedalishchnogo nerva s ispol'zovaniem khronicheskoi neirostimulyatsii i endoskopicheskoi tekhniki.

OBJECTIVE: Sciatic nerve injury in the deep gluteal space is a major clinical problem due to microsurgical manipulations in this region are limited in scope. We offer new endoscopic approach to the sciatic nerve in the deep gluteal space which allows to perform microsurgical manipulations, neurophysiological mapping and electrode installation for the chronic nerve stimulation. MATERIAL AND METHOD: 3 patients with sciatic neuropathy have been operated. Before the operation they suffered from neuropathic pain in the the posterior thigh and calf, reaching 7-8 points on the visual analog scale (VAS). Paresis of triceps surae and biceps femur also was occurred. We performed endoscopic approach to the deep gluteal space through a small incision under the gluteal fold. Microsurgical external and internal decompression of sciatic nerve was performed under the endoscopic control. Next, intra-trunk nerve mapping was performed to visualize sensory fibers. Cylindrical electrodes for chronic neurostimulation were directly placed on the sensory fibers of sciatic nerve. RESULTS: Pain relief was obtained in all cases after activating the simulator, the patient noted a 50% reduction in pain. Muscle straight restoration was observed in all cases 2-3 months later. The clinical effect was stable in the follow up (6 months). CONCLUSION: This technique, combining minimal invasiveness and intraoperative neurophysiological control, makes it possible to optimally position the electrode, both to achieve positive analgesic effect and for potential restoration of nerve function.

Mechanical properties of the sciatic nerve following combined transplantation of analytically extracted acellular allogeneic nerve and adipose-derived mesenchymal stem cells.

PURPOSE: To investigate the effects of Chemically Extracted Acellular Nerves (CEANs) when combined with Adipose-Derived mesenchymal Stem Cell (ADSC) transplantation on the repair of sciatic nerve defects in rabbits. METHODS: A total of 71 six-month-old Japanese rabbit were used in this study. Twenty rabbits served as sciatic nerve donors, while the other 51 rabbits were randomly divided into Autologous Nerve Transplantation Group (ANT, n=17), CEAN group (n=17) and CEAN-ADSCs group (n=17). In all these groups, the rabbit's left sciatic nerves were injured before the experiment, and the uninjured sciatic nerves on their right side were used as the control (CON). Electrophysiological tests were carried out and sciatic nerves were prepared for histomorphology and stretch testing at 24 weeks post-transplant. RESULTS: There were significant differences between ANT and Con groups in amplitude (AMP): P=0.031; motor nerve conduction velocity (MNCV): P=0.029; Maximum stress: P=0.029; and Maximum strain P=0.027. There were also differences between the CEAN and CEAN+ADSCs groups in AMP: P=0.026, MNCV: P=0.024; Maximum stress: P=0.025 and Maximum strain: P=0.030. No significant differences in these parameters were observed when comparing the ANT and CEAN+SACN groups (MNCV: P=0.071) or the CEAN and ANT groups (Maximum stress: P=0.069; Maximum strain P=0.077). CONCLUSION: Addition of ADSCs has a significant impact on the recovery of nerve function, morphology, and tensile mechanical properties following sciatic nerve injury.

Effectiveness of electrical stimulation on nerve regeneration after crush injury: Comparison between invasive and non-invasive stimulation.

Several studies have investigated the use of invasive and non-invasive stimulation methods to enhance nerve regeneration, and varying degrees of effectiveness have been reported. However, due to the use of different parameters in these studies, a fair comparison between the effectiveness of invasive and non-invasive stimulation methods is not possible. The present study compared the effectiveness of invasive and non-invasive stimulation using similar parameters. Eighteen Sprague Dawley rats were classified into three groups: the iES group stimulated with fully implantable device, the tES group stimulated with transcutaneous electrical nerve stimulation (TENS), and the injury group (no stimulation). The iES and tES groups received stimulation for 6 weeks starting immediately after the injury. Motor function was evaluated using the sciatic functional index (SFI) every week. The SFI values increased over time in all groups; faster and superior functional recovery was observed in the iES group than in the tES group. Histological evaluation of the nerve sections and gastrocnemius muscle sections were performed every other week. The axon diameter and muscle fiber area in the iES group were larger, and the g-ratio in the iES group was closer to 0.6 than those in the tES group. To assess the cause of the difference in efficiency, a 3D rat anatomical model was used to simulate the induced electric fields in each group. A significantly higher concentration and intensity around the sciatic nerve was observed in the iES group than in the tES group. Vector field distribution showed that the field was orthogonal to the sciatic nerve spread in the tES group, whereas it was parallel in the iES group; this suggested that the tES group was less effective in nerve stimulation. The results indicated that even though rats in the TENS group showed better recovery than those in the injury group, it cannot replace direct stimulation yet because rats stimulated with the invasive method showed faster recovery and superior outcomes. This was likely attributable to the greater concentration and parallel distribution of electric field with respect to target nerve.

[Gluteal compartment syndrome after immobilization following opioid abuse]. / Gluteales Kompartmentsyndrom nach Liegetrauma bei Opiatabusus.

This article reports the case of a 42-year-old male patient, who sustained a gluteal compartment syndrome after drug-induced immobilization with subsequent rhabdomyolysis and sciatic nerve palsy. Unlike compartment syndrome of the forearm or lower leg, this is a rare condition. After immediate surgical decompression and installation of negative pressure wound treatment, hemofiltration in acute renal failure could be averted using forced diuresis. The sensorimotor function of the lower extremity improved already after the first treatment and secondary wound closure was possible after 1 week. The patient was discharged 11 days after admission with complete recovery of sensorimotor and renal functions.

Magnetic particle templating of hydrogels: engineering naturally derived hydrogel scaffolds with 3D aligned microarchitecture for nerve repair.

OBJECTIVE: Hydrogel scaffolds hold promise for a myriad of tissue engineering applications, but often lack tissue-mimetic architecture. Therefore, in this work, we sought to develop a new technology for the incorporation of aligned tubular architecture within hydrogel scaffolds engineered from the bottom-up. APPROACH: We report a platform fabrication technology-magnetic templating-distinct from other approaches in that it uses dissolvable magnetic alginate microparticles (MAMs) to form aligned columnar structures under an applied magnetic field. Removal of the MAMs yields scaffolds with aligned tubular microarchitecture that can promote cell remodeling for a variety of applications. This approach affords control of microstructure diameter and biological modification for advanced applications. Here, we sought to replicate the microarchitecture of the native nerve basal lamina using magnetic templating of hydrogels composed of glycidyl methacrylate hyaluronic acid and collagen I. MAIN RESULTS: Magnetically templated hydrogels were characterized for particle alignment and micro-porosity. Overall MAM removal efficacy was verified by 96.8% removal of iron oxide nanoparticles. Compressive mechanical properties were well-matched to peripheral nerve tissue at 0.93 kPa and 1.29 kPa, respectively. In vitro, templated hydrogels exhibited approximately 36% faster degradation over 12 h, and were found to guide axon extension from dorsal root ganglia. Finally, in a pilot in vivo study utilizing a 10 mm rat sciatic nerve defect model, magnetically templated hydrogels demonstrated promising results with qualitatively increased remodeling and axon regeneration compared to non-templated controls. SIGNIFICANCE: This simple and scalable technology has the flexibility to control tubular microstructure over long length scales, and thus the potential to meet the need for engineered scaffolds for tissue regeneration, including nerve guidance scaffolds.

Mechanical properties of the sciatic nerve following combined transplantation of analytically extracted acellular allogeneic nerve and adipose-derived mesenchymal stem cells

Abstract Purpose To investigate the effects of Chemically Extracted Acellular Nerves (CEANs) when combined with Adipose-Derived mesenchymal Stem Cell (ADSC) transplantation on the repair of sciatic nerve defects in rabbits. Methods A total of 71 six-month-old Japanese rabbit were used in this study. Twenty rabbits served as sciatic nerve donors, while the other 51 rabbits were randomly divided into Autologous Nerve Transplantation Group (ANT, n=17), CEAN group (n=17) and CEAN-ADSCs group (n=17). In all these groups, the rabbit's left sciatic nerves were injured before the experiment, and the uninjured sciatic nerves on their right side were used as the control (CON). Electrophysiological tests were carried out and sciatic nerves were prepared for histomorphology and stretch testing at 24 weeks post-transplant. Results There were significant differences between ANT and Con groups in amplitude (AMP): P=0.031; motor nerve conduction velocity (MNCV): P=0.029; Maximum stress: P=0.029; and Maximum strain P=0.027. There were also differences between the CEAN and CEAN+ADSCs groups in AMP: P=0.026, MNCV: P=0.024; Maximum stress: P=0.025 and Maximum strain: P=0.030. No significant differences in these parameters were observed when comparing the ANT and CEAN+SACN groups (MNCV: P=0.071) or the CEAN and ANT groups (Maximum stress: P=0.069; Maximum strain P=0.077). Conclusion Addition of ADSCs has a significant impact on the recovery of nerve function, morphology, and tensile mechanical properties following sciatic nerve injury.

Roles of Collagen XXV and Its Putative Receptors PTPσ/δ in Intramuscular Motor Innervation and Congenital Cranial Dysinnervation Disorder.

Intramuscular motor innervation is an essential process in neuromuscular development. Recently, mutations in COL25A1, encoding CLAC-P/collagen XXV, have been linked to the development of a congenital cranial dysinnervation disorder (CCDD). Yet the molecular mechanisms of intramuscular innervation and the etiology of CCDD related to COL25A1 have remained elusive. Here, we report that muscle-derived collagen XXV is indispensable for intramuscular innervation. In developing skeletal muscles, Col25a1 expression is tightly regulated by muscle excitation. In vitro and cell-based assays reveal a direct interaction between collagen XXV and receptor protein tyrosine phosphatases (PTPs) σ and δ. Motor explant assays show that expression of collagen XXV in target cells attracts motor axons, but this is inhibited by exogenous PTPσ/δ. CCDD mutations attenuate motor axon attraction by reducing collagen XXV-PTPσ/δ interaction. Overall, our study identifies PTPσ/δ as putative receptors for collagen XXV, implicating collagen XXV and PTPσ/δ in intramuscular innervation and a developmental ocular motor disorder.

Sciatic Nerve Intraneural Hematoma.

Intraneural hematomas are an uncommon cause of a focal mononeuropathy. When they do occur, it is usually in the setting of inherited or iatrogenic coagulopathies or as a consequence of injections targeting nerves. We report a man aged 68 years on warfarin therapy for a prior pulmonary embolism who presented with a 6-month history of progressive weakness of knee flexion and ankle movement, excruciating pain, and dense numbness in his posterior left thigh and below the knee, consistent with a severe high sciatic palsy. Imaging depicted a contiguous cystic mass of mixed T1 and T2 intensities involving the left sciatic nerve in the thigh, which was radiologically interpreted as a hip arthroplasty-associated pseudotumor. The patient underwent surgical exploration, which revealed a thick hemorrhagic pseudocompartment within the sciatic nerve. The histopathologic diagnosis was consistent with chronic hemorrhage. These impressive lesions should be included in the differential diagnosis of nerve masses.