Fascicular Structure Research Articles

Enhancing facial nerve regeneration with scaffold-free conduits engineered using dental pulp stem cells and their endogenous, aligned extracellular matrix.

Objective. Engineered nerve conduits must simultaneously enhance axon regeneration and orient axon extension to effectively restore function of severely injured peripheral nerves. The dental pulp contains a population of stem/progenitor cells that endogenously express neurotrophic factors (NTFs), growth factors known to induce axon repair. We have previously generated scaffold-free dental pulp stem/progenitor cell (DPSC) sheets comprising an aligned extracellular matrix (ECM). Through the intrinsic NTF expression of DPSCs and the topography of the aligned ECM, these sheets both induce and guide axon regeneration. Here, the capacity of bioactive conduits generated using these aligned DPSC sheets to restore function in critical-sized nerve injuries in rodents was evaluated.Approach. Scaffold-free nerve conduits were formed by culturing DPSCs on a substrate with aligned microgrooves, inducing the cells to align and deposit an aligned ECM. The sheets were then detached from the substrate and assembled into scaffold-free cylindrical tissues.Main results. In vitroanalyses confirmed that scaffold-free DPSC conduits maintained an aligned ECM and had uniformly distributed NTF expression. Implanting the aligned DPSC conduits across critical-sized defects in the buccal branch of rat facial nerves resulted in the regeneration of a fascicular nerve-like structure and myelinated axon extension across the injury site. Furthermore, compound muscle action potential and stimulated whisker movement measurements revealed that the DPSC conduit treatment promoted similar functional recovery compared to the clinical standard of care, autografts. Significance. This study demonstrates that scaffold-free aligned DPSC conduits supply trophic and guidance cues, key design elements needed to successfully promote and orient axon regeneration. Consequently, these conduits restore function in nerve injuries to similar levels as autograft treatments. These conduits offer a novel bioactive approach to nerve repair capable of improving clinical outcomes and patient quality of life.

Ultrasound morphometry of the cervical vagus nerve for daily clinical practice: Reference values for cross sectional area and fascicle count

IntroductionHigh resolution ultrasound (US) of the cervical vagus nerve (CVN) is clinically relevant in the diagnostic workup and during neurostimulation therapy of several neurologic diseases. This prospective study aims to provide reference data of the cross-sectional area (CSA) and fascicle count of the normal CVN and to investigate their possible association with anthropometric data in a large cohort of patients. MethodsA total of 657 CVNs in 330 individuals without history of neurological disease were examined using US (7–15Mhz). The CVN fascicle count and CSA inside the hyperechoic epineurium at the level of the thyroid lobes were measured. Three CSA measurements were performed to calculate the mean value. Anthropometric data were recorded. ResultsThe mean fascicle count was 2.4 ± 1.1 (right) and 2 ± 1 (left) (paired t- test, p < 0.001). Two CVN patterns were identified: A single hypoechoic fascicular structure (26.2 % right, 36.3 % left) and a honeycomb structure of 2–6 discrete fascicles (72.3 % right, 63.7 % left). Right CVN mean CSA was larger compared to left (2.3 ± 1 mm2 and 1.8 ± 0.8 mm2 respectively, t-test, p-0.000). There was no difference in the CSA values between sex and no correlation to age or height. A positive correlation between the CSA and weight and BMI was found (Pearson’s correlation, p = 0.01 right and p = 0.05 left). ConclusionThe right CVN has larger CSA and contains more fascicles than the left. CVN is usually mono- or oligo-fascicular with a honeycomb appearance. The CSA increased with increasing BMI but no age and sex specific differences were noted.

Decellularized Graft for Repairing Severe Peripheral Nerve Injuries in Sheep.

Peripheral nerve injuries resulting in a nerve defect require surgical repair. The gold standard of autograft (AG) has several limitations, and therefore, new alternatives must be developed. The main objective of this study was to assess nerve regeneration through a long gap nerve injury (50 mm) in the peroneal nerve of sheep with a decellularized nerve allograft (DCA). A 5-cm long nerve gap was made in the peroneal nerve of sheep and repaired using an AG or using a DCA. Functional tests were performed once a month and electrophysiology and echography evaluations at 6.5 and 9 months postsurgery. Nerve grafts were harvested at 9 months for immunohistochemical and morphological analyses. The decellularization protocol completely eliminated the cells while preserving the extracellular matrix of the nerve. No significant differences were observed in functional tests of locomotion and pain response. Reinnervation of the tibialis anterior muscles occurred in all animals, with some delay in the DCA group compared with the AG group. Histology showed a preserved fascicular structure in both AG and DCA; however, the number of axons distal to the nerve graft was higher in AG than in DCA. The decellularized graft assayed supported effective axonal regeneration when used to repair a 5-cm long gap in the sheep. As expected, a delay in functional recovery was observed compared with the AG because of the lack of Schwann cells.

Monophasic pericardial synovial sarcoma in a turkish female patient: a very rare case with cyto-histopathological findings

BackgroundThe aim was to present a 35-year-old female patient with diagnosis of monophasic primary pericardial synovial sarcoma (PSS) with cytopathological findings.Case PresentationThe case with back pain, palpitation and weakness, was diagnosed with pericardial effusion and suspicious mass adjacent to right heart in ultrasonography. Computerized tomography showed mass 12 × 11 × 6.5 cm in size, located in right mid-anterior pericardial area, with heterogeneous internal structure, heterogeneously contrasting right heart and prominent pressure on superior vena cava. Cytopathology of pericardial effusion showed monotonous cells with oval-spindle vesicular nuclei, less amphophilic cytoplasm, evenly distributed chromatin and inconspicuous nucleoli. The pericardial mass was resected incompletely, spindle cell mesenchymal tumor with hypercellular fascicular structure and with infiltrative margins, containing a small amount of loose myxoid stroma, occasionally necrotic areas was observed histopathologically. Immunohistochemical positive reaction was for vimentin, Bcl-2, TLE-1. Accordingly, the case was diagnosed with monophasic PSS.ConclusionsThis case of monophasic primary PSS was an extremely rare malignancy diagnosed with the cytopathological findings.

Organ- and function-specific anatomical organization of vagal fibers supports fascicular vagus nerve stimulation

Vagal fibers travel inside fascicles and form branches to innervate organs and regulate organ functions. Existing vagus nerve stimulation (VNS) therapies activate vagal fibers non-selectively, often resulting in reduced efficacy and side effects from non-targeted organs. The transverse and longitudinal arrangement of fibers inside the vagal trunk with respect to the functions they mediate and organs they innervate is unknown, however it is crucial for selective VNS. Using micro-computed tomography imaging, we tracked fascicular trajectories and found that, in swine, sensory and motor fascicles are spatially separated cephalad, close to the nodose ganglion, and merge caudad, towards the lower cervical and upper thoracic region; larynx-, heart- and lung-specific fascicles are separated caudad and progressively merge cephalad. Using quantified immunohistochemistry at single fiber level, we identified and characterized all vagal fibers and found that fibers of different morphological types are differentially distributed in fascicles: myelinated afferents and efferents occupy separate fascicles, myelinated and unmyelinated efferents also occupy separate fascicles, and small unmyelinated afferents are widely distributed within most fascicles. We developed a multi-contact cuff electrode to accommodate the fascicular structure of the vagal trunk and used it to deliver fascicle-selective cervical VNS in anesthetized and awake swine. Compound action potentials from distinct fiber types, and physiological responses from different organs, including laryngeal muscle, cough, breathing, and heart rate responses are elicited in a radially asymmetric manner, with consistent angular separations that agree with the documented fascicular organization. These results indicate that fibers in the trunk of the vagus nerve are anatomically organized according to functions they mediate and organs they innervate and can be asymmetrically activated by fascicular cervical VNS.

Ultrasound appearance of regenerative peripheral nerve interface with clinical correlation.

To describe the ultrasound (US) appearance of regenerative peripheral nerve interfaces (RPNIs) in humans, and correlate clinically and with histologic findings from rat RPNI. Patients (≥ 18years) who had undergone RPNI surgery within our institution between the dates of 3/2018 and 9/2019 were reviewed. A total of 21 patients (15 male, 6 female, age 21-82years) with technically adequate US studies of RPNIs were reviewed. Clinical notes were reviewed for the presence of persistent pain after RPNI surgery. Histologic specimens of RPNIs in a rat model from prior studies were compared with the US findings noted in this study. There was a variable appearance to the RPNIs including focal changes involving the distal nerve, nerve-muscle graft junction, and area of the distal sutures. The muscle grafts varied in thickness with accompanying variable echogenic changes. No interval change was noted on follow-up US studies. Diffuse hypoechoic swelling with loss of the fascicular structure of the nerve within the RPNI and focal hypoechoic changes at the nerve-muscle graft junction were associated with clinical outcomes. US findings corresponded to histologic findings in the rat RPNI. Ultrasound imaging can demonstrate various morphologic changes involving the nerve, muscle, and interface between these two biological components of RPNIs. These changes correspond to expected degenerative and regenerative processes following nerve resection and muscle reinnervation and should not be misconstrued as pathologic in all cases. N5 and N1 morphologic type changes of the RPNI were found to be associated with symptoms.

Repair of Long Nerve Defects with a New Decellularized Nerve Graft in Rats and in Sheep.

Decellularized nerve allografts (DC) are an alternative to autografts (AG) for repairing severe peripheral nerve injuries. We have assessed a new DC provided by VERIGRAFT. The decellularization procedure completely removed cellularity while preserving the extracellular matrix. We first assessed the DC in a 15 mm gap in the sciatic nerve of rats, showing slightly delayed but effective regeneration. Then, we assayed the DC in a 70 mm gap in the peroneal nerve of sheep compared with AG. Evaluation of nerve regeneration and functional recovery was performed by clinical, electrophysiology and ultrasound tests. No significant differences were found in functional recovery between groups of sheep. Histology showed a preserved fascicular structure in the AG while in the DC grafts regenerated axons were grouped in small units. In conclusion, the DC was permissive for axonal regeneration and allowed to repair a 70 mm long gap in the sheep nerve.

Simultaneous Multislice Accelerated TSE for Improved Spatiotemporal Resolution and Diagnostic Accuracy in Magnetic Resonance Neurography: A Feasibility Study.

This study aims to evaluate the utility of simultaneous multislice (SMS) acceleration for routine magnetic resonance neurography (MRN) at 3 T. Patients with multiple sclerosis underwent MRN of the sciatic nerve consisting of a standard fat-saturated T2-weighted turbo spin echo (TSE) sequence using integrated parallel acquisition technique (PAT2) acceleration and 2 T2 TSE sequences using a combination of PAT-SMS acceleration (1) to reduce scan time (PAT2-SMS2; SMS-TSE FAST ) and (2) for time neutral increase of in-plane resolution (PAT1-SMS2; SMS-TSE HR ). Acquisition times were 5:29 minutes for the standard T2 TSE, 3:12 minutes for the SMS-TSE FAST , and 5:24 minutes for the SMS-TSE HR . Six qualitative imaging parameters were analyzed by 2 blinded readers using a 5-point Likert scale and T2 nerve lesions were quantified, respectively. Qualitative and quantitative image parameters were compared, and both interrater and intrarater reproducibility were statistically assessed. In addition, signal-to-noise ratio/contrast-to-noise ratio (CNR) was obtained in healthy controls using the exact same imaging protocol. A total of 15 patients with MS (mean age ± standard deviation, 38.1 ± 11 years) and 10 healthy controls (mean age, 29.1 ± 7 years) were enrolled in this study. CNR analysis was highly reliable (intraclass correlation coefficient, 0.755-0.948) and revealed a significant CNR decrease for the sciatic nerve for both SMS protocols compared with standard T2 TSE (SMS-TSE FAST /SMS-TSE HR , -39%/-55%; P ≤ 0.01). Intrarater and interrater reliability of qualitative image review was good to excellent (κ: 0.672-0.971/0.617-0.883). Compared with the standard T2 TSE sequence, both SMS methods were shown to be superior in reducing pulsatile flow artifacts ( P < 0.01). Ratings for muscle border sharpness, detailed muscle structures, nerve border sharpness, and nerve fascicular structure did not differ significantly between the standard T2 TSE and the SMS-TSE FAST ( P > 0.05) and were significantly better for the SMS-TSE HR than for standard T2 TSE ( P < 0.001). Muscle signal homogeneity was mildly inferior for both SMS-TSE FAST ( P > 0.05) and SMS-TSE HR ( P < 0.001). A significantly higher number of T2 nerve lesions were detected by SMS-TSE HR ( P ≤ 0.01) compared with the standard T2 TSE and SMS-TSE FAST , whereas no significant difference was observed between the standard T2 TSE and SMS-TSE FAST . Implementation of SMS offers either to substantially reduce acquisition time by over 40% without significantly impeding image quality compared with the standard T2 TSE or to increase in-plane resolution for a high-resolution approach and improved depiction of T2 nerve lesions while keeping acquisition times constant. This addresses the specific needs of MRN by providing different imaging approaches for 2D clinical MRN.

Fascicles split or merge every ∼560 microns within the human cervical vagus nerve

Objective. Vagus nerve stimulation (VNS) is Food and Drug Administration-approved for epilepsy, depression, and obesity, and stroke rehabilitation; however, the morphological anatomy of the vagus nerve targeted by stimulatation is poorly understood. Here, we used microCT to quantify the fascicular structure and neuroanatomy of human cervical vagus nerves (cVNs). Approach. We collected eight mid-cVN specimens from five fixed cadavers (three left nerves, five right nerves). Analysis focused on the ‘surgical window’: 5 cm of length, centered around the VNS implant location. Tissue was stained with osmium tetroxide, embedded in paraffin, and imaged on a microCT scanner. We visualized and quantified the merging and splitting of fascicles, and report a morphometric analysis of fascicles: count, diameter, and area. Main results. In our sample of human cVNs, a fascicle split or merge event was observed every ∼560 µm (17.8 ± 6.1 events cm−1). Mean morphological outcomes included: fascicle count (6.6 ± 2.8 fascicles; range 1–15), fascicle diameter (514 ± 142 µm; range 147–1360 µm), and total cross-sectional fascicular area (1.32 ± 0.41 mm2; range 0.58–2.27 mm). Significance. The high degree of fascicular splitting and merging, along with wide range in key fascicular morphological parameters across humans may help to explain the clinical heterogeneity in patient responses to VNS. These data will enable modeling and experimental efforts to determine the clinical effect size of such variation. These data will also enable efforts to design improved VNS electrodes.

Development of a regenerative porous PLCL nerve guidance conduit with swellable hydrogel-based microgrooved surface pattern via 3D printing

Peripheral nerve injury causes severe loss of motor and sensory functions, consequently increasing morbidity in affected patients. An autogenous nerve graft is considered the current gold standard for reconstructing nerve defects and recovering lost neurological functions; however, there are certain limitations to this method, such as limited donor nerve supply. With advances in regenerative medicine, recent research has focused on the fabrication of tissue-engineered nerve grafts as promising alternatives to the autogenous nerve grafts. In this study, we designed a nerve guidance conduit using an electrospun poly(lactide-co-ε-caprolactone) (PLCL) membrane with a visible light-crosslinked gelatin hydrogel. The PLCL nanoporous membrane with permeability served as a flexible and non-collapsible epineurium for the nerve conduit; the inner-aligned gelatin hydrogel paths were fabricated via 3D printing and a photocrosslinking system. The resultant gelatin hydrogel with microgrooved surface pattern was established as a conducting guidance path for the effective regeneration of axons and served as a reservoir that can incorporate and release bioactive molecules. From in vivo performance tests using a rat sciatic nerve defect model, our PLCL/gelatin conduit demonstrated successful axonal regeneration, remyelination capacities and facilitated functional recovery. Hence, the PLCL/gelatin conduit developed in this study is a promising substitute for autogenous nerve grafts. Statement of significanceNerve guidance conduits (NGCs) are developed as promising recovery techniques for bridging peripheral nerve defects. However, there are still technological limitations including differences in the structures and components between natural peripheral nerve and NGCs. In this study, we designed a NGC composed of an electrospun poly(lactide-co-ε-caprolactone) (PLCL) membrane and 3D printed inner gelatin hydrogel to serve as a flexible and non-collapsible epineurium and a conducting guidance path, respectively, to mimic the fascicular structure of the peripheral nerve. In particular, in vitro cell tests clearly showed that gelatin hydrogel could guide the cells and function as a reservoir that incorporate and release nerve growth factor. From in vivo performance tests, our regenerative conduit successfully led to axonal regeneration with effective functional recovery.

Nerve Ultrasound Protocol to Detect Dysimmune Neuropathies.

Nerve ultrasound is increasingly used in the differential diagnosis of polyneuropathy as a complementary tool to nerve conduction studies. Morphological alterations of the peripheral nerves, such as increasing the cross-sectional area (CSA), have been described in various immune-mediated polyneuropathies. The most prominent morphological changes in nerve ultrasound have been described for the chronic inflammatory demyelinating polyneuropathy (CIDP)-spectrum disease. CIDP may be distinguished from hereditary and other polyneuropathies by measuring the extent and pattern of nerve swellings (CSA increase). Typical findings in demyelinating inflammatory neuropathies are multifocal nerve swellings with inhomogeneous fascicular structure, while CSA increase in demyelinating hereditary neuropathies occurs in a more generalized and homogenous manner. In other non-inflammatory axonal neuropathies, nerves can appear with normal or slight CSA increases, especially in typical entrapment sites. This article presents technical requirements for nerve ultrasound, an examination procedure using a standardized examination protocol, current reference values for the CSA, and typical sonographic pathological findings in patients with inflammatory neuropathies.

Mushroom Bodies of Stick and Leaf Insects (Phasmatodea: Insecta): Structure and Sources of Formation

It has been established that mushroom bodies of stick insects are formed by Kenyon cells collected in numerous groups of cells the processes of which originally form individual bundles going into the calyx. The majority of such bundles lose their identity already in the cellular layer, and therefore, complex bundles usually enter the calyx. The merging of bundles progresses in the calyx, and even the peduncle keeps a fascicular structure. Only lobes have a classical concentric structure. In the embryonic period, mushroom bodies are formed by two proliferative centers with one neuroblast per center. It is supposed that the neuroblasts of mushroom bodies of stick insects are neuroblasts of type II and that groups of Kenyon cells are generated by intermediate neural progenitors.

The Effect of Primary Carbide on the Wear Resistance of Fe-Cr-C Coatings

The wear-resistant Fe-Cr-C coating has been widely used in industrial production owing to its high hardness and good comprehensive performance. Its anti-wear ability is mainly owing to the primary chromium carbides solidified during welding. In this study the effect of carbide morphology and distribution on the wear resistance of Fe-Cr-C coatings was investigated through experiment and simulation. In experiments, 3D microstructures of the typical carbides were examined using a high-resolution 3D X-ray computed tomography, and the 3D structures were then used in finite element simulation. Coatings with different morphologies and distributions of primary carbides were investigated. The results show that the fascicular primary chromium carbides break by the shearing stress during wear, leading to transverse fractures, while the mutual support among the homogeneous carbides contributes to the resistance of contact stress of the entire supporting framework, thereby imparting excellent wear resistance. Furthermore, the simulation results from the real 3D microstructure are consistent with the experimental ones. The fascicular structure produces a localized higher strain and larger stress concentration than the homogeneous one, implying higher abrasion loss in the former. These results will be helpful to optimize the structure design and final performance of the anti-wear Fe-Cr-C coatings. It will also be a new application of real-structure FE analysis in the widely used coatings for mining machines.

Anatomical study and histochemical analysis of Artemisia leucodes Schrenk

The study of anatomical structure of the aerial part of Artemisia leucodes Schrenk. was carried out, and in this regard, the anatomical and diagnostic features of A. leucodes raw materials were revealed: epidermal cells of an elongated shape, mesophyll in the leaves is columnar, the stem has a fascicular structure, collenchymal mechanical structures are present in the stem ribs. Histochemical analysis shows that the secretory structures of A. leucodes produce sesquiterpene lactones and essential oils, as was confirmed by a chemical study of the aerial parts of A. leucodes. Sesquiterpene lactones anhydroaustricin, matricarin, leucomisin, grossmizin, 5β(H)-austricin, were isolated from the ethanol extract of A. leucodes by column chromatography on silica gel. By hydrodistillation of anthodium, buds, and leaves an essential oil was obtained, according to chromatography-mass spectrometry, the major component of which was l-camphor - 39.00% and camphene - 9.31%, 1.8-cineole (eucalyptole) - 6.20%. The obtained data on diagnostic features, determination of the localization of secondary metabolites and chemical composition allow us to identify and standardize the medicinal raw materials of A. leucodes, what guarantees quality, and also allow more rational use of A. leucodes in pharmaceutical production.

Reflections on the History of Nerve Repair - Sir Sydney Sunderland's Final Presentation to the Neurosurgical Society of Australasia.

Sir Sydney Sunderland (1910-1993) was an eminent physician and anatomist who identified the fascicular structure of nerves, and developed the eponymous 5-tiered classification of nerve injuries. Not long before his death, he presented a keynote address to the Annual Scientific Meeting of the Neurosurgical Society of Australasia. Recently, the videotape of his presentation was discovered. In the presentation, Sir Sydney included discussion on the history of nerve repair, commencing with Herophilus and Galen, and progressing through the Middle Ages, including Leonardo of Bertapaglia, and he further noted the discoveries during the 1800s of the microscope, the axon, and nerve histology (including Remak, Schwann, Nissl, and Golgi), Waller's findings on nerve degeneration, and nerve injury (His, Cajal, Forsmann, and Harrison). Sir Sydney discussed nerve injuries sustained during World War I, with the deleterious effects of infection, and following the many nerve injuries sustained during World War II, he discussed his own discoveries of internal topography of nerve fascicles, and the anatomical substrate of nerve fascicles that limit surgery for nerve repair, nerve grafts, and the basic science of spinal cord repair. This paper presents a transcript of Sunderland's presentation and includes many of his original images used to illustrate this tour de force of nerve repair.

Micro-grooved nerve guidance conduits combined with microfiber for rat sciatic nerve regeneration

In order to accelerate the regeneration of injured nerves, highly aligned structures that mimic native tissues are essential for nerve guidance conduits (NGC). In this study, a biodegradable porous micro-patterned NGCs were manufactured by use of capillary force lithography and salt leaching method, which filled as wrapped with aligned electrospun microfiber (PA-NGC) using. These combined NGC showed 5μm aligned groove pattern on the interior wall and were filled with 4–5μm align fibers for a fascicular structure to mimic the native nerve. The highly aligned structure has increased PC12 migration and morphological elongation compared with random microfiber. For the in vivo study, we bridged in the 10mm sciatic nerve defect margins with NGC. The PA-NGC were compared to flat NGCs filled with random (FR-NGC) or aligned fiber (FA-NGC) and patterned NGCs filled with random fiber (PR-NGC). The PA-NGC showed as dramatically re-bridged neurofilament and higher sciatic function index, onset-to-peak of amplitude, muscle weight and fiber diameter compared to other groups after 8 weeks of implantation. In our results, the PA-NGC not only can serve as a design for functional NGC without growth factor but also can be used in clinical application for peripheral nerve regeneration.

Selective Wireless Stimulation of Rat Sciatic Nerve.

Chronic stability of functional performance is a significant challenge to the success of implantable devices for neural stimulation and recording. Integrating wireless technology with typical microelectrode array designs is one approach that may reduce instances of mechanical failure and improve the long-term performance of neural devices. We have investigated the long-term stability of Wireless Floating Microelectrode Arrays (WMFAs) implanted in rat sciatic nerve, and their ability to selectively recruit muscles in the hind limb via neural stimulation. Thresholds as low as 4.1 μA were able to generate visible motion of the rear paw. Each implanted device (n=6) was able to selectively recruit plantar flexion and dorsiflexion of the rear paw, and selective stimulation of both movements was achieved throughout the study period. The evoked limb motion was electrode specific and was dependent on location within the fascicular structure of the nerve. Motor thresholds and movement patterns remained stable for more than 8 weeks after device implantation. No major changes in limb function were observed between the implanted and contralateral limb, or between implanted animals and control group animals. The results of this study show that WFMAs with intrafascicular electrodes implanted in a healthy peripheral nerve can provide stable and selective motor recruitment, without altering overall limb function.

Evaluating Microelectrode Arrays in Peripheral Nerve Using Micro Computed Tomography.

Many advances have been made with imaging of implanted neural devices; however, the ability to image whole nerve samples remains limited. Further, few imaging modalities are well suited for visualizing both whole devices in vivo and individual microelectrodes within a nerve. In this study, we used micro-computed tomography (micro-CT) to evaluate Wireless Floating Microelectrode Arrays (WMFAs) implanted in rat sciatic nerve at the level of whole devices and individual electrodes. WFMAs were also used to track selective recruitment of plantar flexion and dorsiflexion of the rear paw, which was achieved by each implanted device (n=6) during chronic implantation. Evoked limb motion was correlated to end-of-study assessments using micro-CT to visualize electrode locations within the fascicular structure of the sciatic nerve. Results of this study show that micro-CT imaging can provide valuable assessments of microelectrode arrays implanted in peripheral nerves for both whole devices visualized in vivo and individual electrodes visualized in whole nerve tissue samples.Clinical relevance- This work informs the use of micro-computed tomography as a tool for correlating neural device performance with physical attributes of the implant location.

High-Resolution Nerve Ultrasound to Assess Nerve Echogenicity, Fascicular Count, and Cross-Sectional Area Using Semiautomated Analysis.

Little is known about echogenicity and fascicular structure observed in high-resolution nerve ultrasound (HRUS) in both healthy subjects and patients with peripheral nerve disease. The aim of this study was to evaluate the reliability of echogenicity, fascicle count, and fascicle size analysis, to create standard values and compare these parameters to patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Median, ulnar, radial, tibial, and fibular nerve of 79 healthy subjects and patients were scanned by one examiner using HRUS. Image analysis regarding echogenicity, fascicle count, and fascicle cross-sectional area (CSA) was performed by two independent raters semiautomatically using ImageJ. Pearson correlation coefficient r reflected interrater reliability (IR), and intraclass correlation coefficient (ICC) determined intrarater reliability (IAR). Results of healthy subjects were compared to 20 patients with CIDP by analysis of variance. IR was very good for echogenicity (r = .9) and good for fascicle count and size of the largest fascicle (r = .64/.56). IAR was very good for all three parameters (ICC = .9/.83/.74). Healthy subjects had a wide range of values. CIDP patients were in range of healthy subjects. Clinically progressive CIDP patients (defined as an increase in Overall Disability Sum Score by ≥1 point) had a lower fraction of black than healthy controls and stable CIDP patients (P < .001). Semiautomated evaluation of echogenicity, fascicle count, and fascicle CSA is reliable. Cutoff values to differentiate between healthy persons and CIDP do not exist. Echogenicity is useful for detecting clinically progressive CIDP patients and should be used in clinical context or intraindividual course.

Mitochondrial activity disruption and local muscle damage induced in mice by Scolopendra polymorpha venom.

Background: Scolopendra polymorpha (S. polymorpha) is a predatory centipede whose venom contains a multiplicity of biochemical effectors that can cause muscle damage and cumulative cell destruction in its prey. Despite previous investigations of S. polymorpha and other centipede venoms, there is a lack of information on the morphological and biochemical patterns elicited by their myotoxic effects. To elucidate these processes, this paper presents evidence of skeletal muscle damage, and alterations in key biochemical mediators that appear only after exposure to centipede venom.Methods:Venom was collected and fractionated using RP-HPLC; mouse extensor digitorum longus (EDL) muscle was exposed to whole venom and venom fractions to evaluate myotoxicity by means of creatine kinase (CK) - a muscle damage marker - activity measurements and histochemical analysis.Results:CK activity was higher in EDL muscle exposed to venom than in unexposed muscle. This increase was observed after 15 min of venom incubation, and remained stable up to 45 min. Venom-exposed EDL muscle showed signs of muscle damage including necrosis, loss of fascicular structure as well as mitochondrial accumulations and ragged red fibers (RRF), suggesting an impairment in the normal mitochondrial arrangement. Nicotinamide adenine dinucleotide (NADH) and cytochrome oxidase (COX) tests also indicate that respiratory complexes might be affected.Conclusion:Our results suggest a different biochemical composition of S. polymorpha venom, based on the different effects of four venom fractions on the cells tested, according to statistical evidence. Fractions F6 and F7 caused the most important alterations.