Functional outcomes of nerve allografts augmented with mesenchymal stem cells and surgical angiogenesis in a rat sciatic nerve defect model.

BACKGROUND: Motor function recovery following acellular nerve allograft (ANA) repair remains inferior to autologous nerve reconstruction. We investigated the functional recovery of ANAs after combined mesenchymal stem cell (MSC) delivery and surgical angiogenesis in a rat sciatic nerve defect model. METHODS: In 100 Lewis rats, unilateral sciatic nerve defects were reconstructed with (I) autografts, (II) ANAs, (III) ANAs wrapped with a superficial inferior epigastric artery fascial (SIEF) flap, combined with either (IV) undifferentiated MSCs or (V) Schwann cell-like differentiated MSCs. The tibialis anterior muscle area was evaluated during the survival period using ultrasonography. Functional recovery, histomorphometry, and immunofluorescence were assessed at 12 and 16 weeks. RESULTS: At 12 weeks, the addition of surgical angiogenesis and MSCs improved ankle contractures. The SIEF flap also significantly improved compound muscle action potential (CMAP) outcomes compared with ANAs. Autografts outperformed all groups in muscle force and weight. At 16 weeks, ankle contractures of ANAs remained inferior to autografts and SIEF, whereas the CMAP amplitude was comparable between groups. The muscle force of autografts remained superior to all other groups, and the muscle weight of ANAs remained inferior to autografts. No differences were found in histomorphometry outcomes between SIEF groups and ANAs. Vascularity, determined by CD34 staining, was significantly higher in SIEF groups compared with ANAs. CONCLUSIONS: The combination of surgical angiogenesis and MSCs did not result in a synergistic improvement in functional outcomes. In a short nerve gap model, the adipofascial flap may provide sufficient MSCs to ANAs without additional ex vivo MSC seeding.

Curcumin reduces blood-nerve barrier abnormalities and cytotoxicity to endothelial cells and pericytes induced by cisplatin.

BACKGROUND: Cisplatin is a platinum-based antineoplastic agent used to treat cancers of solid organs. Neuropathy is one of its major side effects, necessitating dose reduction or cessation. Previous studies suggested that cisplatin causes microvascular toxicity, including pericyte detachment. This study aimed to clarify whether these alterations occurred in the blood-nerve barrier (BNB) of capillaries after cisplatin treatment. MATERIALS AND METHODS AND RESULTS: Electron microscopic analysis of rat sciatic nerves with cisplatin neuropathy showed increased frequency and severity of pericyte detachment. Moreover, the vascular basement membrane did not tightly encircle around the endothelial cells and pericytes. Cultured human umbilical vein endothelial cells and human brain vascular pericytes showed reduced viability, increased caspase-3 activity and enhanced oxidative stress following cisplatin treatment. In addition, cisplatin decreased transendothelial electrical resistance (TEER) and the expression of the tight junction proteins occludin and zonula occludens-1. Curcumin, a polyphenol found in the root of Curcuma longa, had favourable effects on cisplatin neuropathy in previous work. Therefore, curcumin was tested to determine whether it had any effect on these abnormalities. Curcumin alleviated pericyte detachment, cytotoxicity, oxidative stress, TEER reduction and tight junction protein expression. CONCLUSIONS: These data indicate that cisplatin causes BNB disruption in the nerves and might result in neuropathy. Curcumin might improve neuropathy via the restoration of BNB. Whether alterations in the BNB occur and curcumin is effective in patients with cisplatin neuropathy remain to be investigated.

Morphometric analysis of the epineurial and endoneurial blood vessels of the human sciatic nerve in relation to aging.

The aim of this research is to perform an analysis of the epineurial and endoneurial blood vessels in relation to aging. The research is conducted on samples of the human sciatic nerve of 12 case (age from 27 to 89). The histological sections are stained by streptavidin-biotin method of detecting the presence of Type IV collagen. After morphometric analysis the following stereological parameters have been calculated: the number of blood vessels per unit of area, the volume density of the blood vessels and the surface density of the blood vessels of the epineurium and endoneurium. An additional diameter measurement is performed for the endoneural blood vessels. In order to perform a more detailed analysis, the cases were classified into three age groups, the first (27-48 years), the second (49-70 years) and, the third (over 70 years). The bivariate correlation analysis showed that the number of blood vessels of the endoneurium, their volume and surface densities in relation to age produced a statistically significant positive correlation. One Way ANOVA test demonstrated a statistically significant increase in the number of endoneurial blood vessels in the age group III when compared the age group I and, in addition, it showed a significant decrease in the diameter of the age group II when compared to the age group I. Paired t - test shows a statistically significant higher number of endoneurial blood vessels in relation to the epineurial, namely, in the age group III. The volume and surface density of the epineurial blood vessels is significantly higher than the endoneurial in both the I and II age group. Age brings about significant changes of the endoneurial vascular network of the sciatic nerve due to the increase in density of the endoneurial blood vessels, their volume and surface densities. Consequently, in the cases older than 70 years, the number of endoneurial blood vessels significantly exceeds the number of epineurial blood vessels.

Direct Comparison of Therapeutic Effects on Diabetic Polyneuropathy between Transplantation of Dental Pulp Stem Cells and Administration of Dental Pulp Stem Cell-Secreted Factors.

Stem cell transplantation is a potential novel therapy for diabetic polyneuropathy. Dental pulp stem cells (DPSCs) are attractive stem cell sources because DPSCs can be isolated from extracted teeth and cryopreserved while retaining viability. In this study, we directly compared the efficacy of the transplantation of DPSCs and the administration of the secreted factors from DPSCs (DPSC-SFs) on diabetic polyneuropathy. Eight weeks after streptozotocin injection, DPSCs (1.0 × 106 cells/rat) or DPSC-SFs (1.0 mL/rat) were administered into the unilateral hindlimb skeletal muscles of diabetic Sprague-Dawley rats. DPSC transplantation and DPSC-SF administration did not affect blood glucose levels and body weights in the diabetic rats. Both DPSC transplantation and DPSC-SF administration significantly ameliorated sciatic nerve conduction velocity and sciatic nerve blood flow, accompanied by increases in muscle bundle size, vascular density in the skeletal muscles and intraepidermal nerve fiber density in the diabetic rats, while there was no difference between the results for DPSCs and DPSC-SFs. These results suggest that the efficacy of both DPSC transplantation and DPSC-SF administration for diabetic polyneuropathy four weeks after transplantation/administration was mainly due to the multiple secretomes secreted from transplanted DPSCs or directly injected DPSC-SFs in the early phase of transplantation/administration.

Revascularization patterns of nerve allografts in a rat sciatic nerve defect model.

INTRODUCTION: The specific patterns of revascularization of allograft nerves after the addition of vascularization remain unknown. The aim of this study was to determine the revascularization patterns of optimized processed allografts (OPA) after surgically induced angiogenesis to the wound bed in a rat sciatic nerve model. MATERIALS AND METHODS: In 51 Lewis rats, sciatic nerve gaps were repaired with (i) autografts, (ii) OPA and (iii) OPA wrapped in a pedicled superficial inferior epigastric artery fascia flap (SIEF) to provide vascularization to the wound bed. At 2, 12, and 16 weeks, the vascular volume and vascular surface area in nerve samples were measured using micro CT and photography. Cross-sectional images were obtained and the number of vessels was quantified in the proximal, mid, and distal sections of the nerve samples. RESULTS: At 2 weeks, the vascular volume of SIEF nerves was comparable to control (P = 0.1). The vascular surface area in SIEF nerves was superior to other groups (P<0.05). At 12 weeks, vascularity in SIEF nerves was significantly higher than allografts (P<0.05) and superior compared to all other groups (P<0.0001) at 16 weeks. SIEF nerves had a significantly increased number of vessels compared to allografts alone in the proximal (P<0.05) and mid-section of the graft (P<0.05). CONCLUSIONS: Addition of surgical angiogenesis to the wound bed greatly improves revascularization. It was demonstrated that revascularization occurs primarily from proximal to distal (proximal inosculation) and not from both ends as previously believed and confirms the theory of centripetal revascularization.

New methods for objective angiogenesis evaluation of rat nerves using microcomputed tomography scanning and conventional photography.

INTRODUCTION: Nerve regeneration involves multiple processes, which enhance blood supply that can be promoted by growth factors. Currently, tools are lacking to visualize the vascularization patterns in transplanted nerves in vivo. The purpose of this study was to describe three-dimensional visualization of the vascular system in the rat sciatic nerve and to quantify angiogenesis of nerve reconstruction. MATERIALS AND METHODS: In 12 Lewis rats (weighing 250-300 g), 10 mm sciatic nerve gaps were repaired with ipsilateral reversed autologous nerve grafts. At 12 and 16 weeks of sacrifice, Microfil® contrast compound was injected in the aorta. Nerve autografts (N = 12) and contralateral untreated nerves (N = 12) were harvested and cleared while preserving the vasculature. The amount of vascularization was measured by quantifying the vascular surface area using conventional photography (two-dimensional) and the vascular volume was calculated with microcomputed tomography (three-dimensional). For each measurement, a vessel/nerve area ratio was calculated and expressed in percentages (vessel%). RESULTS: The vascular volume measured 3.53 ± 0.43% in autografts and 4.83 ± 0.45% vessels in controls at 12 weeks and 4.95 ± 0.44% and 6.19 ± 0.29% vessels at 16 weeks, respectively. The vascular surface area measured 25.04 ± 2.77% in autografts and 26.87 ± 2.13% vessels in controls at 12 weeks, and 28.11 ± 3.47% and 33.71 ± 2.60% vessels at 16 weeks, respectively. The correlation between both methods was statistically significant (p = .049). CONCLUSIONS: Both methods are considered to successfully reflect the degree of vascularization. Application of this technique could be used to visualize and objectively quantify angiogenesis of the transplanted nerve graft. Moreover, this simple method is easily reproducible and could be extrapolated to any other desired target organ ex vivo in small animals to investigate the vascular network.

Evolutionary aspects on the origin, distribution and ramifications of the ischiadicus nerve in the giant anteater (Myrmecophaga tridactyla) / Aspectos evolutivos sobre as origens, distribuições e ramificações dos nervos isquiáticos do tamanduá-bandeira (Myrmecophaga tridactyla)

This work aimed to describe the origin, distribution, and ramifications of the ischiadicus nerve in the giant anteater and to provide anatomical data which could explain not only the evolutionary aspects but also provide important information for other related works. For the present study, four specimens were used, prepared by perfusion of 10% formaldehyde solution via the femoral artery, for conservation and dissection. The origin of the right and left ischiadicus nerves in the giant anteater from the ventral ramification of the third lumbar (L3) and the first (S1), second (S2), and third (S3) sacral spinal nerves. These nerves were symmetrical in all animals studied. The distribution and ramification occurred to the superficial, middle, and deep gluteal, gemelli, piriform, quadratus femoris, tensor fasciae latae, caudal crural abductor, cranial and caudal parts of the biceps femoris, adductor, semitendinous, and cranial and caudal parts of the semimembranous muscles. Based on the origins of the ischiadicus nerves, there is a caudal migration in the nerve location in animals in a more recent position on the evolutionary scale due to reconfiguration of the lumbosacral plexus, resulting from the increase in a number of lumbar vertebrae. There is no complete homology of the muscle innervation.(AU)

Objetivou-se descrever as origens, distribuições e ramificações dos nervos isquiáticos no tamanduá-bandeira, disponibilizando, assim, dados anatômicos que possam não só elucidar os aspectos evolutivos como também fornecer informações importantes para áreas afins. Foram utilizados quatro espécimes preparados por meio da perfusão de formaldeído 10% via artéria femoral, para conservação e dissecação. As origens dos nervos isquiáticos direito e esquerdo no tamanduá-bandeira foram provenientes dos ramos ventrais dos nervos espinhais lombares três e sacrais um, dois e três, sendo simétricos em todos os animais estudados. As distribuições e ramificações ocorreram nos músculos glúteos superficial, médio e profundo; gêmeo; piriforme; quadrado femoral; tensor da fáscia lata; abdutor crural caudal; bíceps femoral parte cranial; bíceps femoral parte caudal; adutor; semitendíneo; semimembranáceo parte cranial e semimembranáceo parte caudal. Notou-se que houve uma migração caudal na localização deste nervo nos animais mais recentes na escala evolutiva, devido a uma reconfiguração do plexo lombossacral decorrente do aumento no número de vértebras lombares, não havendo uma homologia total quanto à inervação dos músculos.(AU)

Conditioned media from dental pulp stem cells improved diabetic polyneuropathy through anti-inflammatory, neuroprotective and angiogenic actions: Cell-free regenerative medicine for diabetic polyneuropathy.

AIMS/INTRODUCTION: Dental pulp stem cells (DPSCs) can be easily obtained from teeth for general orthodontic reasons. We have previously reported the therapeutic effects of DPSC transplantation for diabetic polyneuropathy. As abundant secretomes from DPSCs are considered to play a central role in the improvement of diabetic polyneuropathy, we investigated whether direct injection of DPSC-conditioned media (DPSC-CM) into hindlimb skeletal muscles ameliorates diabetic polyneuropathy in diabetic rats. MATERIALS AND METHODS: DPSCs were isolated from the dental pulp of Sprague-Dawley rats. Eight weeks after the induction of diabetes, DPSC-CM was injected into the unilateral hindlimb skeletal muscles in both normal and diabetic rats. The effects of DPSC-CM on diabetic polyneuropathy were assessed 4 weeks after DPSC-CM injection. To confirm the angiogenic effect of DPSC-CM, the effect of DPSC-CM on cultured human umbilical vascular endothelial cell proliferation was investigated. RESULTS: The administration of DPSC-CM into the hindlimb skeletal muscles significantly ameliorated sciatic motor/sensory nerve conduction velocity, sciatic nerve blood flow and intraepidermal nerve fiber density in the footpads of diabetic rats. We also showed that DPSC-CM injection significantly increased the capillary density of the skeletal muscles, and suppressed pro-inflammatory reactions in the sciatic nerves of diabetic rats. Furthermore, an in vitro study showed that DPSC-CM significantly increased the proliferation of umbilical vascular endothelial cells. CONCLUSIONS: We showed that DPSC-CM injection into hindlimb skeletal muscles has a therapeutic effect on diabetic polyneuropathy through neuroprotective, angiogenic and anti-inflammatory actions. DPSC-CM could be a novel cell-free regenerative medicine treatment for diabetic polyneuropathy.

Angiopoietin-1/Tie2 signaling pathway contributes to the therapeutic effect of thymosin ß4 on diabetic peripheral neuropathy.

Angiopoietin-1 (Ang1) and its receptor Tie2 regulate vascular function. Our previous study demonstrated that thymosin beta 4 (Tß4) ameliorates neurological function of diabetic peripheral neuropathy. Mechanisms underlying the therapeutic effect of Tß4 on diabetic peripheral neuropathy have not been fully investigated. The present in vivo study investigated whether the Ang1/Tie2 signaling pathway is involved in Tß4-improved neurovascular remodeling in diabetic peripheral neuropathy. Diabetic BKS. Cg-m+/+Leprdb/J (db/db) mice at age 20 weeks were treated with Tß4 and neutralizing antibody against mouse Tie2 for 4 consecutive weeks. Neurological functional and neurovascular remodeling were measured. Administration of the neutralizing antibody against Tie2 attenuated the therapeutic effect of Tß4 on improved diabetic peripheral neuropathy as measured by motor and sensory nerve conduction velocity and thermal hypoesthesia compared to diabetic db/db mice treated with Tß4 only. Histopathological analysis revealed that the neutralizing antibody against Tie2 abolished Tß4-increased microvascular density in sciatic nerve and intraepidermal nerve fiber density, which were associated with suppression of Tß4-upregulated occludin expression and Tß4-reduced protein levels of nuclear factor-κB (NF-κB) and vascular cell adhesion molecule-1 (VCAM1). Our data provide in vivo evidence that the Ang1/Tie2 pathway contributes to the therapeutic effect of Tß4 on diabetic peripheral neuropathy.

Netrin-1 improves adipose-derived stem cell proliferation, migration, and treatment effect in type 2 diabetic mice with sciatic denervation.

BACKGROUND: Diabetic peripheral neurovascular diseases (DPNVs) are complex, lacking effective treatment. Autologous/allogeneic transplantation of adipose-derived stem cells (ADSCs) is a promising strategy for DPNVs. Nonetheless, the transplanted ADSCs demonstrate unsatisfying viability, migration, adhesion, and differentiation in vivo, which reduce the treatment efficiency. Netrin-1 secreted as an axon guidance molecule and served as an angiogenic factor, demonstrating its ability in enhancing cell proliferation, migration, adhesion, and neovascularization. METHODS: ADSCs acquired from adipose tissue were modified by Netrin-1 gene (NTN-1) using the adenovirus method (N-ADSCs) and proliferation, migration, adhesion, and apoptosis examined under high-glucose condition. The sciatic denervated mice (db/db) with type 2 diabetes mellitus (T2DM) were transplanted with N-ADSCs and treatment efficiency assessed based on the laser Doppler perfusion index, immunofluorescence, and histopathological assay. Also, the molecular mechanisms underlying Netrin-1-mediated proliferation, migration, adhesion, differentiation, proangiogenic capacity, and apoptosis of ADSCs were explored. RESULTS: N-ADSCs improved the proliferation, migration, and adhesion and inhibited the apoptosis of ADSCs in vitro in the condition of high glucose. The N-ADSCs group demonstrated an elevated laser Doppler perfusion index in the ADSCs and control groups. N-ADSCs analyzed by immunofluorescence and histopathological staining demonstrated the distribution of the cells in the injected limb muscles, indicating chronic ischemia; capillaries and endothelium were formed by differentiation of N-ADSCs. The N-ADSCs group showed a significantly high density of the microvessels than the ADSCs group. The upregulation of AKT/PI3K/eNOS/P-38/NF-κB signaling pathways and secretion of multiple growth factors might explain the positive effects of Netrin-1 on ADSCs. CONCLUSION: The overexpression of Netrin-1 in ADSCs improves proliferation, migration, and treatment effect in type 2 diabetic mice with sciatic denervation, which directs the clinical treatment of patients with DPNVs.

Blood flow index as an indicator of successful sciatic nerve block: a prospective observational study using laser speckle contrast imaging.

BACKGROUND: Laser speckle contrast imaging allows real-time, non-invasive, quantitative measurements of regional blood flow. The objectives of this prospective observational study were to use laser speckle contrast imaging to evaluate blood flow changes after sciatic nerve block, and to determine whether this novel optical technique can evaluate block success. METHODS: This observational study included 63 adult patients undergoing elective lower limb surgery with sciatic nerve block. Blood flow images and blood flow index (BFI) values of toes were recorded using laser speckle contrast imaging 5 min before nerve block and at 5 min intervals until 30 min after sciatic block. The sensitivity, specificity, and cut-off value of laser speckle contrast imaging for predicting successful sciatic block were determined by receiver operator characteristic (ROC) curve analysis. RESULTS: The BFI values of toes were significantly increased at each time point after successful sciatic block, compared with the baseline value obtained 5 min before nerve block; in failed sciatic block, there were no significant differences. For successful sciatic block, the highest increase of BFI value was at the big toe. BFI increase of the big toe at 10 min after sciatic block has great potential as an indicator of block success. The area under the ROC curve was 0.954 at a cut-off value of 8.48 perfusion units (PU) with a sensitivity of 89% and a specificity of 100%. CONCLUSIONS: Laser speckle contrast imaging might be an early, objective, quantitative, and reliable indicator of successful sciatic block. BFI increase of the big toe not reaching 8.48 PU within 10 min after sciatic block indicates block failure. CLINICAL TRIAL REGISTRATION: NCT03169517.

Wide-Field Functional Microscopy of Peripheral Nerve Injury and Regeneration.

Severe peripheral nerve injuries often result in partial repair and lifelong disabilities in patients. New surgical techniques and better graft tissues are being studied to accelerate regeneration and improve functional recovery. Currently, limited tools are available to provide in vivo monitoring of changes in nerve physiology such as myelination and vascularization, and this has impeded the development of new therapeutic options. We have developed a wide-field and label-free functional microscopy platform based on angiographic and vectorial birefringence methods in optical coherence tomography (OCT). By incorporating the directionality of the birefringence, which was neglected in the previously reported polarization-sensitive OCT techniques for nerve imaging, vectorial birefringence contrast reveals internal nerve microanatomy and allows for quantification of local myelination with superior sensitivity. Advanced OCT angiography is applied in parallel to image the three-dimensional vascular networks within the nerve over wide-fields. Furthermore, by combining vectorial birefringence and angiography, intraneural vessels can be discriminated from those of the surrounding tissues. The technique is used to provide longitudinal imaging of myelination and revascularization in the rodent sciatic nerve model, i.e. imaged at certain sequential time-points during regeneration. The animals were exposed to either crush or transection injuries, and in the case of transection, were repaired using an autologous nerve graft or acellular nerve allograft. Such label-free functional imaging by the platform can provide new insights into the mechanisms that limit regeneration and functional recovery, and may ultimately provide intraoperative assessment in human subjects.

The contribution of muscarinic-receptor-mediated responses to epineurial vascular diameter at the sciatic nerve.

This study used an anaesthetized rat model to directly observe changes in diameter of the vessels supplying the sciatic nerve in response to acetylcholine (10-4 M), a muscarinic receptor agonist, and atropine (10-5 M), a muscarinic receptor antagonist. Topical application of acetylcholine resulted in increases in vessel diameter (baseline: 22.0 ± 2.5 µm, acetylcholine: 28.8 ± 3.3 µm), while topical application of atropine resulted in a decrease in diameter (baseline: 26.6 ± 3.2 µm, atropine: 15.5 ± 3.6 µm) of the epineurial vessels. Mean arterial pressure was not affected by either acetylcholine (baseline: 103.8 ± 1.8 mm Hg, acetylcholine: 102.8 ± 3.2 mm Hg) or atropine (baseline: 104.0 ± 1.9 mm Hg, atropine: 105.2 ± 2.2 mm Hg). These data suggest that muscarinic-receptor-mediated responses can affect the diameter of the epineurial vessels at the sciatic nerve. In addition, muscarinic-receptor-mediated responses appear to contribute to baseline diameter of epineurial vessels at the sciatic nerve.

Anti-VEGF treatment improves neurological function in tumors of the nervous system.

Research of various diseases of the nervous system has shown that VEGF has direct neuroprotective effects in the central and peripheral nervous systems, and indirect effects on improving neuronal vessel perfusion which leads to nerve protection. In the tumors of the nervous system, VEGF plays a critical role in tumor angiogenesis and tumor progression. The effect of anti-VEGF treatment on nerve protection and function has been recently reported - by normalizing the tumor vasculature, anti-VEGF treatment is able to relieve nerve edema and deliver oxygen more efficiently into the nerve, thus reducing nerve damage and improving nerve function. This review aims to summarize the divergent roles of VEGF in diseases of the nervous system and the recent findings of anti-VEGF therapy in nerve damage/regeneration and function in tumors, specifically, in Neurofibromatosis type 2 associated schwannomas.

MicroRNA-146a Mimics Reduce the Peripheral Neuropathy in Type 2 Diabetic Mice.

MicroRNA-146a (miR-146a) regulates multiple immune diseases. However, the role of miR-146a in diabetic peripheral neuropathy (DPN) has not been investigated. We found that mice (db/db) with type 2 diabetes exhibited substantial downregulation of miR-146a in sciatic nerve tissue. Systemic administration of miR-146a mimics to diabetic mice elevated miR-146a levels in plasma and sciatic nerve tissue and substantially increased motor and sensory nerve conduction velocities by 29 and 11%, respectively, and regional blood flow by 50% in sciatic nerve tissue. Treatment with miR-146a mimics also considerably decreased the response in db/db mice to thermal stimuli thresholds. Histopathological analysis showed that miR-146a mimics markedly augmented the density of fluorescein isothiocyanate-dextran-perfused blood vessels and increased the number of intraepidermal nerve fibers, myelin thickness, and axonal diameters of sciatic nerves. In addition, miR-146a treatment reduced and increased classically and alternatively activated macrophage phenotype markers, respectively. Analysis of miRNA target array revealed that miR-146a mimics greatly suppressed expression of many proinflammatory genes and downstream related cytokines. Collectively, our data indicate that treatment of diabetic mice with miR-146a mimics robustly reduces DPN and that suppression of hyperglycemia-induced proinflammatory genes by miR-146a mimics may underlie its therapeutic effect.

Anatomical and MR correlative study of the proximal sciatic nerve vasculature.

OBJECTIVE: The aim of our study is to demonstrate that increased T2 signal on MRI could be due to intraneural vessels in asymptomatic individuals, and may therefore be a normal finding. METHODS: An initial anatomic cadaveric study was undertaken to gain a better understanding of the vascular supply of the proximal sciatic nerve. Secondly, a retrospective study of MR imaging of patients without sciatic symptoms was performed to assess the prevalence of intraneural vessels, defined as hyperintensity on at least three consecutive slices on both T2 and gadolinium enhanced T1 weighted imaging, visible on routine MSK pelvic imaging. RESULTS: The anatomical study demonstrated a relatively abundant blood supply in the peri-ischiatic region. In the MR study, 20/76 (26%) patients showed visible intraneural vessels. More than one intraneural vessel was depicted in two of the sciatic nerves. Direct branching between the extrinsic and intrinsic systems was seen in only five cases. CONCLUSION: Normal intraneural vessels can frequently be seen within the sciatic nerve on routine musculoskeletal pelvic imaging. Advances in knowledge: T2 hyperintensity in the proximal sciatic nerve can be due to intraneural vessels and should not necessarily be reported as abnormal.

A potential contribution of tenascin-X to blood vessel formation in peripheral nerves.

Tenascin-X (TNX), an extracellular matrix protein, is abundantly expressed in peripheral nerves. However, the physiological role of TNX in peripheral nerves remains unknown. In this study, we found that actin levels in sciatic nerves of TNX-deficient mice were markedly decreased. Since actin was highly expressed in endothelial cells in wild-type sciatic nerves, we assessed morphological alterations of blood vessels in TNX-null sciatic nerves. The density of blood vessels was significantly decreased and the size of blood vessels was larger than those in wild-type sciatic nerves. Immunofluorescence showed that TNX was expressed by Schwann cells and fibroblasts in sciatic nerves. The results suggest that TNX secreted from Schwann cells and/or fibroblasts is involved in blood vessel formation in peripheral nerves.

The protective effect of the active components of ERPC on diabetic peripheral neuropathy in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Euonymus alatus, Radix trichosanthis, Panax notoginseng and Coptis chinensis are popular plants used in traditional Chinese medicine to treat diabetes. AIM OF THE STUDY: The aim of the study is to investigate the therapeutic effect of the active components of Euonymus alatus, Radix trichosanthis, Panax notoginseng and Coptis chinensis (cERPC) on diabetic peripheral neuropathy in the rats and explore the underlying mechanism involved. METHODS: After diabetes was induced in rats for 20 weeks, cERPC or water was administered for 12 weeks. After a hot plate test, motor nerve conduction velocity and sciatic nerve blood flow were determined; the sciatic nerves were isolated for toluidine blue staining; and the fibre area, fibre diameter, axon area, axon diameter and myelin thickness were evaluated. The levels of the myelin basic protein, myelin protein zero, Oct6 and Krox20 were measured by western blot or immunofluorescence. RESULTS: cERPC was efficient in reducing the response latency, increasing motor nerve conduction velocity, enhancing sciatic nerve blood flow and ameliorating the pathological changes in diabetic rats. cERPC also had a role in increasing the levels of myelin basic protein and myelin protein zero and improving the expression of Oct6 and Krox20 in sciatic nerves of diabetic rats. CONCLUSIONS: cERPC ameliorates diabetic peripheral neuropathy by attenuating electrophysiological, circulatory and morphological alterations, which is mediated by the Oct6-Krox20 pathway.