Density Of Myelinated Fibers Research Articles

Quantification of Nerve Viscosity Using Shear Wave Dispersion Imaging in Diabetic Rats: A Novel Technique for Evaluating Diabetic Neuropathy.

ObjectiveViscoelasticity is an essential feature of nerves, although little is known about their viscous properties. The discovery of shear wave dispersion (SWD) imaging has presented a new approach for the non-invasive evaluation of tissue viscosity. The present study investigated the feasibility of using SWD imaging to evaluate diabetic neuropathy using the sciatic nerve in a diabetic rat model.Materials and MethodsThis study included 11 diabetic rats in the diabetic group and 12 healthy rats in the control group. Bilateral sciatic nerves were evaluated 3 months after treatment with streptozotocin. We measured the nerve cross-sectional area (CSA), nerve stiffness using shear wave elastography (SWE), and nerve viscosity using SWD imaging. The motor nerve conduction velocity (MNCV) was also measured. These four indicators and the histology of the sciatic nerves were then compared between the two groups. The performance of CSA, SWE, and SWD imaging in distinguishing the two groups was assessed using receiver operating characteristic (ROC) analysis.ResultsNerve CSA, stiffness, and viscosity in the diabetic group was significantly higher than those in the control group (all p < 0.05). The results also revealed a significantly lower MNCV in the diabetic group (p = 0.005). Additionally, the density of myelinated fibers was significantly lower in the diabetic group (p = 0.004). The average thickness of the myelin sheath was also lower in the diabetic group (p = 0.012). The area under the ROC curve for distinguishing the diabetic neuropathy group from the control group was 0.876 for SWD imaging, which was significantly greater than 0.677 for CSA (p = 0.030) and 0.705 for SWE (p = 0.035).ConclusionSciatic nerve viscosity measured using SWD imaging was significantly higher in diabetic rats. The viscosity measured using SWD imaging performed well in distinguishing the diabetic neuropathy group from the control group. Therefore, SWD imaging may be a promising method for the evaluation of diabetic neuropathy.

Microstructural Periventricular White Matter Injury in Post-hemorrhagic Ventricular Dilatation.

The neurologic deficits of neonatal post-hemorrhagic hydrocephalus (PHH) have been linked to periventricular white matter injury. To improve understanding of PHH-related injury, diffusion basis spectrum imaging (DBSI) was applied in neonates, modeling axonal and myelin integrity, fiber density, and extrafiber pathologies. Objectives included characterizing DBSI measures in periventricular tracts, associating measures with ventricular size, and examining MRI findings in the context of postmortem white matter histology from similar cases. A prospective cohort of infants born very preterm underwent term equivalent MRI, including infants with PHH, high-grade intraventricular hemorrhage without hydrocephalus (IVH), and controls (very preterm [VPT]). DBSI metrics extracted from the corpus callosum, corticospinal tracts, and optic radiations included fiber axial diffusivity, fiber radial diffusivity, fiber fractional anisotropy, fiber fraction (fiber density), restricted fractions (cellular infiltration), and nonrestricted fractions (vasogenic edema). Measures were compared across groups and correlated with ventricular size. Corpus callosum postmortem immunohistochemistry in infants with and without PHH assessed intra- and extrafiber pathologies. Ninety-five infants born very preterm were assessed (68 VPT, 15 IVH, 12 PHH). Infants with PHH had the most severe white matter abnormalities and there were no consistent differences in measures between IVH and VPT groups. Key tract-specific white matter injury patterns in PHH included reduced fiber fraction in the setting of axonal or myelin injury, increased cellular infiltration, vasogenic edema, and inflammation. Specifically, measures of axonal injury were highest in the corpus callosum; both axonal and myelin injury were observed in the corticospinal tracts; and axonal and myelin integrity were preserved in the setting of increased extrafiber cellular infiltration and edema in the optic radiations. Increasing ventricular size correlated with worse DBSI metrics across groups. On histology, infants with PHH had high cellularity, variable cytoplasmic vacuolation, and low synaptophysin marker intensity. PHH was associated with diffuse white matter injury, including tract-specific patterns of axonal and myelin injury, fiber loss, cellular infiltration, and inflammation. Larger ventricular size was associated with greater disruption. Postmortem immunohistochemistry confirmed MRI findings. These results demonstrate DBSI provides an innovative approach extending beyond conventional diffusion MRI for investigating neuropathologic effects of PHH on neonatal brain development.

Correlation analysis of electroneuromyographic, functional-anatomical and morphometric indicators of regeneration of the injured sciatic nerve

Objective. To study the electrophysiological, functional-anatomical and morphometric indicators of the sciatic nerve regeneration after complete transection and connection of the nerve stumps with epineural sutures and adhesives. Materials and methods. The experiments were carried out on white outbred male rats. The efficiency of sciatic nerve regeneration was investigated with the standard 4-6 epineural sutures and the use of polyethylene glycol hydrogel Duraseal or Tisseel fibrin glue with 2 fixation sutures. On the 14th, 30th and 60th days after the complete transection of the sciatic nerve and subsequent connection of the nerve stumps with epineural sutures, hydrogel or fibrin glue, limb function was assessed using SFI test and ENMG. The distal segment of the nerve was sampled for electron microscopic and morphometric studies. The density of the regenerated myelinated nerve fibers was studied and a correlation analysis was performed with the results of SFI test and ENMG. Results. The use of adhesives provides a similar result of connecting the transected sciatic nerve, as in standard neurorrhaphy, and regeneration of myelinated nerve fibers in the distal nerve. The regeneration density of myelinated nerve fibers significantly increased on the 30 th and 60th days in the groups in which Duraseal hydrogel and Tisseel fibrin glue were used, without a statistically significant difference in ENMG parameters (M-response amplitude, nerve conduction velocity, latency period) and the result of SFI test. The amplitude of M-response on the 30th day was statistically significantly lower after the connection of nerve stumps with Tisseel fibrin glue in comparison with the Duraseal hydrogel, whereas on the 60th day there was no difference according to the results of electrophysiological studies. Conclusions. The efficiency of sciatic nerve regeneration after the combined connection exceeds the standard technique, and the results of pathophysiological assessments are more often correlated with morphometry data on the 30th day.

Combining chitin biological conduits with small autogenous nerves and platelet-rich plasma for the repair of sciatic nerve defects in rats.

AimsPeripheral nerve defects are often difficult to recover from, and there is no optimal repair method. Therefore, it is important to explore new methods of repairing peripheral nerve defects. This study explored the efficacy of nerve grafts constructed from chitin biological conduits combined with small autogenous nerves (SANs) and platelet‐rich plasma (PRP) for repairing 10‐mm sciatic nerve defects in rats.MethodsTo prepare 10‐mm sciatic nerve defects, SANs were first harvested and PRP was extracted. The nerve grafts consisted of chitin biological conduits combined with SAN and PRP, and were used to repair rat sciatic nerve defects. These examinations, including measurements of axon growth efficiency, a gait analysis, electrophysiological tests, counts of regenerated myelinated fibers and observations of their morphology, histological evaluation of the gastrocnemius muscle, retrograde tracing with Fluor‐Gold (FG), and motor endplates (MEPs) distribution analysis, were conducted to evaluate the repair status.ResultsTwo weeks after nerve transplantation, the rate and number of regenerated axons in the PRP‐SAN group improved compared with those in the PRP, SAN, and Hollow groups. The PRP‐SAN group exhibited better recovery in terms of the sciatic functional index value, composite action potential intensity, myelinated nerve fiber density, myelin sheath thickness, and gastrectomy tissue at 12 weeks after transplantation, compared with the PRP and SAN groups. The results of FG retrograde tracing and MEPs analyses showed that numbers of FG‐positive sensory neurons and motor neurons as well as MEPs distribution density were higher in the PRP‐SAN group than in the PRP or SAN group.ConclusionsNerve grafts comprising chitin biological conduits combined with SANs and PRP significantly improved the repair of 10‐mm sciatic nerve defects in rats and may have therapeutic potential for repairing peripheral nerve defects in future applications.

Low-Intensity Pulsed Ultrasound Prompts Both Functional and Histologic Improvements While Upregulating the Brain-Derived Neurotrophic Factor Expression after Sciatic Crush Injury in Rats

The aim of this study was to determine that low-intensity pulsed ultrasound (LIPUS) at an intensity of 140 mW/cm2 promotes functional and histologic improvements in sciatic nerve crush injury in a rat model and to investigate changes over time in relevant growth factors and receptors, exploring the mechanism of LIPUS in the recovery process after injury. Toe angle in the toe-off phase, regenerative axonal length, myelinated nerve fiber density, diameter of myelinated nerve fiber, axon diameter and myelin sheath thickness were significantly higher in the LIPUS group than in the sham group. Gene and protein expression of brain-derived neurotrophic factor (BDNF) was upregulated in the LIPUS group. In conclusion, LIPUS contributed to rapid functional and histologic improvement and upregulated BDNF expression after sciatic nerve crush injury in rats.

Scattered Light Imaging: Resolving the substructure of nerve fiber crossings in whole brain sections with micrometer resolution

For developing a detailed network model of the brain based on image reconstructions, it is necessary to spatially resolve crossing nerve fibers. The accuracy hereby depends on many factors, including the spatial resolution of the imaging technique. 3D Polarized Light Imaging (3D-PLI) allows the three-dimensional reconstruction of nerve fiber tracts in whole brain sections with micrometer in-plane resolution, but leaves uncertainties in pixels containing crossing fibers. Here we introduce Scattered Light Imaging (SLI) to resolve the substructure of nerve fiber crossings. The measurement is performed on the same unstained histological brain sections as in 3D-PLI. By illuminating the brain sections from different angles and measuring the transmitted (scattered) light under normal incidence, light intensity profiles are obtained that are characteristic for the underlying brain tissue structure. We have developed a fully automated evaluation of the intensity profiles, allowing the user to extract various characteristics, like the individual directions of in-plane crossing nerve fibers, for each image pixel at once. We validate the reconstructed nerve fiber directions against results from previous simulation studies, scatterometry measurements, and fiber directions obtained from 3D-PLI. We demonstrate in different brain samples (human optic tracts, vervet monkey brain, rat brain) that the 2D fiber directions can be reliably reconstructed for up to three crossing nerve fiber bundles in each image pixel with an in-plane resolution of up to 6.5 μm. We show that SLI also yields reliable fiber directions in brain regions with low 3D-PLI signals coming from regions with a low density of myelinated nerve fibers or out-of-plane fibers. This makes Scattered Light Imaging a promising new imaging technique, providing crucial information about the organization of crossing nerve fibers in the brain.

Conventional histomorphometry and fast free of acrylamide clearing tissue (FACT) visualization of sciatic nerve in chicken (Gallus domesticus).

Histomorphometry and use of the fast free of acrylamide clearing tissue (FACT) protocol were studied on the sciatic nerve in chicken (Gallus domesticus). In the first part of the study, the sciatic nerves of 20 chickens of four age groups (7, 14, 26 and 40 days) were studied (n=5 birds per age class). Their sciatic nerve samples were stained with Hematoxylin and Eosin and Masson's trichrome and were histomorphometrically evaluated. In the second part of the study, FACT protocol was applied on the sciatic nerve of a 26 days old chicken. After clearing of 1.00 mm-thick sciatic nerve sections, they were immunolabelled using Hoechst for nuclei staining and recorded by a Z-stack motorized fluorescent microscope. In the conventional histo-morphometry, the epineurium, perineurium and endoneurium were thicker and the nerve bundle diameter was bigger in the left sciatic nerve of chicken of all age groups compared to the right sciatic nerve. On the contrary, the axon diameter and the myelinated nerve fiber diameter were bigger, the myelin sheath was thicker, the nodes of Ranvier intervals were higher and the density of myelinated nerve fibers was also higher in the right sciatic nerve compared to the left one. In conclusion, histomorphometric parameters in the left and right sciatic nerve during chicken growth were significantly different. Furthermore, the FACT protocol could be used for the 3D imaging of the chicken sciatic nerve and its immunostained evaluation.

Local Riluzole Release from a Thermosensitive Hydrogel Rescues Injured Motoneurons through Nerve Root Stumps in a Brachial Plexus Injury Rat Model.

The C5-C6 nerve roots are usually spared from avulsion after brachial plexus injury (BPI) and can thus be used as donors for nerve repair. A BPI rat model with C5-C6 nerve root stumps has been established in our previous work. The aim of this study was to test whether riluzole loaded into a thermosensitive hydrogel could applied locally in the nerve root stumps of this BPI rat model, thus increasing the reparative effect of the nerve root stumps. Nile red (a hydrophobic dye) was used as a substitute for riluzole since riluzole itself does not emit light. Nile red, loaded into a thermosensitive hydrogel, was added to the nerve root stumps of the BPI rat model. Additionally, eighteen rats, with operation on right brachial plexus, were evenly divided into three groups: control (Con), thermosensitive hydrogel (Gel) and thermosensitive hydrogel loaded with riluzole (Gel + Ri) groups. Direct nerve repair was performed after local riluzole release for two weeks. Functional and electrophysiological evaluations and histological assessments were used to evaluate the reparative effect 8 weeks after nerve repair. Nile red was slowly released from the thermosensitive hydrogel and retrograde transport through the nerve root stumps to the motoneurons, according to immunofluorescence. Discernible functional recovery began earlier in the Gel + Ri group. The compound muscle action potential, ChAT-expressing motoneurons, positivity for neurofilaments and S100, diameter of regenerating axons, myelin sheath thickness and density of myelinated fibers were markedly increased in the Gel + Ri group compared with the Con and Gel groups. Our results indicate that the local administration of riluzole could undergo retrograde transportation through C5-C6 nerve root stumps, thereby promoting neuroprotection and increasing nerve regeneration.

MiR-17-92 enriched exosomes derived from multipotent mesenchymal stromal cells enhance axon-myelin remodeling and motor electrophysiological recovery after stroke

MiR-17-92 cluster enriched exosomes derived from multipotent mesenchymal stromal cells (MSCs) increase functional recovery after stroke. Here, we investigate the mechanisms underlying this recovery. At 24 h (h) post transient middle cerebral artery occlusion, rats received control liposomes or exosomes derived from MSCs infected with pre-miR-17-92 expression lentivirus (Exo-miR-17-92+) or control lentivirus (Exo-Con) intravenously. Compared to the liposomes, exosomes significantly reduced the intracortical microstimulation threshold current of the contralateral cortex for evoking impaired forelimb movements (day 21), increased the neurite and myelin density in the ischemic boundary area, and contralesional axonal sprouting into the caudal forelimb area of ipsilateral side and in the denervated spinal cord (day 28), respectively. The Exo-miR-17-92+ further enhanced axon-myelin remodeling and electrophysiological recovery compared with the EXO-Con. Ex vivo cultured rat brain slice data showed that myelin and neuronal fiber density were significantly increased by Exo-miR-17-92+, while significantly inhibited by application of the PI3K/Akt/mTOR pathway inhibitors. Our studies suggest that the miR-17-92 cluster enriched MSC exosomes enhanced neuro-functional recovery of stroke may be attributed to an increase of axonal extension and myelination, and this enhanced axon-myelin remodeling may be mediated in part via the activation of the PI3K/Akt/mTOR pathway induced by the downregulation of PTEN.

A novel tissue engineered nerve graft constructed with autologous vein and nerve microtissue repairs a long-segment sciatic nerve defect.

Veins are easy to obtain, have low immunogenicity, and induce a relatively weak inflammatory response. Therefore, veins have the potential to be used as conduits for nerve regeneration. However, because of the presence of venous valves and the great elasticity of the venous wall, the vein is not conducive to nerve regeneration. In this study, a novel tissue engineered nerve graft was constructed by combining normal dissected nerve microtissue with an autologous vein graft for repairing 10-mm peripheral nerve defects in rats. Compared with rats given the vein graft alone, rats given the tissue engineered nerve graft had an improved sciatic static index, and a higher amplitude and shorter latency of compound muscle action potentials. Furthermore, rats implanted with the microtissue graft had a higher density and thickness of myelinated nerve fibers and reduced gastrocnemius muscle atrophy compared with rats implanted with the vein alone. However, the tissue engineered nerve graft had a lower ability to repair the defect than autogenous nerve transplantation. In summary, although the tissue engineered nerve graft constructed with autologous vein and nerve microtissue is not as effective as autologous nerve transplantation for repairing long-segment sciatic nerve defects, it may nonetheless have therapeutic potential for the clinical repair of long sciatic nerve defects. This study was approved by the Experimental Animal Ethics Committee of Chinese PLA General Hospital (approval No. 2016-x9-07) on September 7, 2016.

Structural Changes in the Posterior Interosseous Nerve from Patients with Wrist Osteoarthritis and Asymptomatic Controls

Background Posttraumatic morphological changes have been described in the posterior interosseous nerve (PIN) after mild wrist trauma, and it has been suggested that posttraumatic nerve changes may contribute to wrist pain. PIN excision has shown to relieve pain in some patients with wrist osteoarthritis. However, is not known if PINs from osteoarthritic wrist have pathological features. Objective The aim of this study was to investigate whether PINs from osteoarthritic wrists show morphological changes that are not present in healthy wrists. Materials and Methods PINs resected from 15 osteoarthritic wrists were analyzed with light microscopy regarding morphological changes and compared with five asymptomatic controls without osteoarthritis. Results No significant differences in fascicular area, myelinated fiber density or myelinated fiber diameter were found. However, most patients and controls exhibited some degree of pathology, and a few samples from both groups exhibited severe pathological changes. Conclusions Our findings of morphological changes in both patients with osteoarthritis and asymptomatic controls suggest that pathological changes of unknown significance might exist in the general population in the PIN at wrist level. We believe that the observed structural nerve changes in the PIN are unlikely to contribute to the symptoms of pain. Further studies of the normal histological appearance of the terminal PIN are needed. Level of Evidence This is Level II study.

879 Novel injectable coolant for reducing cutaneous nerve fiber density

Postherpetic neuralgia (PHN) is a dermatologic disorder with no established cure. The distinct dermatomal distribution of PHN makes the peripheral nerve supplying the dermatome and its distal cutaneous branches the ideal therapeutic target; however, the short acting nature of current medications limits the use of this localized approach. Herein we demonstrate the effects of a drug-free, injectable coolant with long-lasting pain suppression capabilities that could potentially be used for treatment of PHN. We have previously reported reduced cutaneous nerve fiber density following topical cooling with cryolipolysis treatment. From here we went on to develop an injectable coolant to target nerves at any anatomic location accessible by a needle. We showed that injection of coolant around the rat sciatic nerve leads to local disruption of myelin. This in turn leads to decrease in nocifensive function for up to 60 days. In this study, using the rat sciatic nerve, we examined the mechanism of reduced nociceptive response after coolant injection. We investigated the effects of the injectable coolant on sciatic nerve branches distal to the injection site and on cutaneous nerve fibers using Coherent anti-Stokes Raman scattering (CARS) microscopy and immunofluorescence (IF) staining. CARS showed myelin degradation in branches distal to the injection site. Corrected correlation parameter index, an indicator for organization of myelin structure, decreased in fibular branch from 0.86±0.08 at baseline to 0.40±0.22 (P<0.0001) at day 14 post injection. Myelinated dermal nerve fiber density was quantified in skin of the hind paw innervated by the sciatic nerve. IF staining showed decreased density of myelinated dermal nerve fibers from baseline value of 56±3/mm2 to 22±3/mm2 (P<0.0001) at day 14. Thus, coolant injection reduces pain by decreasing cutaneous nerve fiber density. Although more work needs to be done, we hope this could potentially be used to treat PHN associated pain.

A quantitative evaluation of sciatic nerve stiffness after compression by shear wave elastography in diabetic rats.

BackgroundOur study investigates the feasibility of using quantitative evaluation for nerve entrapment visualization by shear wave elastography (SWE) in diabetic rats.MethodsA total of 24 male Sprague-Dawley (SD) rats were included in this study. Before injection of streptozotocin (STZ), the experimental groups were assigned as the diabetic nerve compression (DNC) group (DNC, n=18) and the control group (CON, n=6). The DNC model was created by wrapping a silicone tube around the nerve, and then the DNC group was divided into the DNC 2-week (DNC2W, n=6), 4-week (DNC4W, n=6), and 8-week (DNC8W, n=6) groups according to the different duration time of sciatic nerve compression. The nerve stiffness was detected by SWE. Meanwhile, motor nerve conduction velocity (MNCV) was detected. These 2 indicators and histology of sciatic nerves were compared across the different groups.ResultsThe stiffness of the nerve depicted by SWE at the compression site increased markedly along with the duration time of compression (P<0.01). The MNCV decreased along with the duration time of nerve compression (P<0.05). The nerve stiffness depicted by SWE was negatively correlated with MNCV (r=−0.926; P<0.01). Myelinated fiber density significantly decreased as the duration time of nerve compression increased (P<0.01). Some differences were found between DNC4W and DNC8W groups, and CON and DNC2W groups (P<0.05) in average axon diameter, myelin sheath thickness, and g ratio.ConclusionsThe increased values of SWE, along with the increased duration of nerve compression, could reflect the severity of nerve entrapment in diabetic rats. Therefore, SWE may be used as a noninvasive and effective method to quantitatively evaluate the severity of diabetic nerve entrapment.

Peri‐implant myelinated nerve fibers: Histological findings in dogs

While osseointegration following various dental implant placement protocols has been extensively investigated, the neurohistological integration has received little attention. The primary aim of this study was to compare the myelinated nerve fibers density in peri-implant bone tissue following various implant placement protocols. The secondary aim assessed the effect of follow-up on peri-implant nerve fibers density. Ten beagle dogs randomly received 68 commercially pure titanium implants in the mandibular premolar or molar regionbilaterally following extraction utilizingone of the six treatment protocols: (a) immediate implant placement (IIP) and immediate loading (IL); (b) IIP and delayed loading (DL); (c) IIP and left unloaded (UL); (d) delayed implant placement (DIP) and IL; (e) DIP and DL; and (f) DIP and UL. Histomorphometric analysis of the peri-implant myelinated nerve fibers was performed in a 300μm peri-implant zone at the cervical, middle, and apical level following implant placement. The follow-up assessment involved longitudinal observation at 3months following each implant treatment protocol and at 6months for IIP+IL and IIP+DL protocols. The influence of different treatment protocols, including the fixed effects of implant groups (IIP+IL, IIP+DL, IIP+UL, DIP+IL, DIP+DL, DIP+UL) and regions (cervical, middle, apical), was examined via a linear mixed model. The IIP+IL group showed a significantly higher myelinated nerve density compared to the IIP+UL and DIP+UL group. Peri-implant nerve re-innervation was significantly higher (P=.002) in the apical region compared to the cervical region. After immediate implant placement, the IL group showed a significantly (P=.03) higher density of myelinated nerve fibers compared to DL. No significant (P=.19) effect of follow-up on nerve density was observed. The immediate implant placement and loading protocol showed most beneficial effect on peri-implant innervation with highest myelinated nerve density in the apical region. A longer loading time had no influence on the peri-implant nerve density.

Effect of the local application of stem cells on repairing facial nerve defects: a systematic review

To systematically evaluate the repairing effect of stem cells on facial nerve defects. Articles regarding the regenerating effect of stem cells on facial nerves in animals were collected from the databases of Pubmed, Cochrane Library, Web of Science, Embase, Scopus, and CBM. Two professionals independently completed the article screening, data extraction, and bias risk assessment. RevMan 5.3 and random-effects models were used for the statistical analysis, and the results were presented in the form of mean differences (MD) with a 95%CI. The results of functional evaluation (vibrissae movement, facial paralysis) and histological evaluation (density of myelinated fibers, diameter of fibers, thickness of myelin sheath, G ratio) of facial nerve were Meta-analyzed. A total of 4 614 articles were retrieved from the 6 databases, and 15 of these articles were included in the Meta-analysis. For vibrissae movement and facial paralysis, the stem cell group scored significantly higher than the non-stem cell group (P<0.05). The density of myelinated fibers and thickness of the myelin sheath in the stem cell group were higher than those in the non-stem cell group (P<0.05). The G ratio in the stem cell group was smaller than that in the non-stem cell group (P=0.001). There was no significant difference in fiber diameter (P=0.08). Stem cells have potential in promoting facial nerve regeneration.

Platelet-Rich Plasma Combined with Low-Dose Ultrashort Wave Therapy Accelerates Peripheral Nerve Regeneration.

Finding treatments that accelerate peripheral nerve regeneration, prolongation, and functional recovery remains a challenging task. Platelet-rich plasma (PRP) contains numerous growth factors and active proteins, and low-dose ultrashort waves (USWs) stimulate the formation of nerve-nourishing vessels, which are powerful for nerve regeneration. The goal of this study was to evaluate the synergistic effects of serial ultrasound-guided PRP injections combined with low-dose USWs radiation on peripheral nerve regeneration in a crush injury model. Fifty rabbits were equally and randomly divided into normal control, model, USW, PRP, and PRP+USW groups. The neurological function, electrophysiological recovery, and histological and morphological evaluation of regenerated nerves, as well as a targeted muscle recovery assessment, were performed to investigate the regenerative effect of PRP combined with USW therapy. Our results showed that the PRP+USW group had the better early axonal regeneration and displayed the earliest positive compound muscle action potential among the treatment groups. At postintervention week 12, a histological evaluation showed similar expression of the S-100 protein in the PRP+USW and normal control groups. Moreover, the morphological assessment revealed a significant increase in the myelinated nerve fiber density and diameter and myelin sheath thickness compared with the USW and PRP groups. The morphometry of the target muscles indicated the lowest reduction in the percent volume in the PRP+USW group, and an ultrasound examination of the targeted muscle showed the best improvement in stiffness and perfusion parameters at 12 weeks after crush injury. Thus, serial ultrasound-guided PRP injections combined with low-dose USW radiation exert a synergistic effect on accelerating functional axon recovery and decreasing atrophy of the target muscles in a crush injury model. Impact Statement This research describes that the application of platelet-rich plasma combined with low-dose ultrashort waves treatment exert a synergistic effect on accelerating peripheral nerve regeneration. With the extensive use of platelet-rich plasma and physical factors in regenerative medicine or clinical rehabilitation medicine, our findings may help establish effective strategies for repairing peripheral nerve injury.

Intraneural IFG-1 in Cryopreserved Nerve Isografts Increase Neural Regeneration and Functional Recovery in the Rat Sciatic Nerve.

Insulin-like growth factor 1 (IGF-1) was found to stimulate Schwann cell mitosis. Exogenous IGF-1 may improve nerve regeneration after cryopreservation. To evaulate the effect of intraneural administration of IGF-1 in cryopreserved nerve isografts. Eighteen millimeter grafts were used for bridging an 18-mm defect in the rat sciatic nerve. A total of 57 rats were randomly divided into three groups: (1) autograft (Group 1); (2) cryopreserved isograft (Group 2); (3) cryopreserved isograft with intraneural IGF-1 administration (Group 3). 12 weeks after surgery, functional recovery (Sciatic functional index [SFI], Swing speed [SS], nerve conduction velocity [NCV], amplitude of compound motor action potentials [CMAP], and gastrocnemius muscle index [GMI]) and nerve regeneration (myelin sheath area, total fiber counts, fiber density, and fiber width) were all evaluated. The intraneural injection of IGF-1 significantly improved SFI and SS at weeks 10 and 12. There were no statistical differences between Groups 1 and 3 in any of the SFI or SS evaluations. CMAP and NCV in Group 1 were significantly higher than in Groups 2 and 3, and Group 3 had significantly higher CMAP and NCV compared to Group 2. No significant differences were found in fiber width. The number of nerve fibers, percentage of myelinated fibers, fiber density, and GMI was significantly higher in Group 1 compared to Group 2, but no significant differences were found between Groups 1 and 3. The results show that intraneural injection of IGF-1 in an 18 mm cryopreserved isograft improve axonal regeneration and functional recovery.

Sex Differences in the Effect of Alcohol Drinking on Myelinated Axons in the Anterior Cingulate Cortex of Adolescent Rats.

Cognitive deficits associated with teenage drinking may be due to disrupted myelination of prefrontal circuits. To better understand how alcohol affects myelination, male and female Wistar rats (n = 7–9/sex/treatment) underwent two weeks of intermittent operant self-administration of sweetened alcohol or sweetened water early in adolescence (postnatal days 28–42) and we tested for macro- and microstructural changes to myelin. We previously reported data from the males of this study showing that alcohol drinking reduced myelinated fiber density in layers II–V of the anterior cingulate division of the medial prefrontal cortex (Cg1); herein, we show that myelinated fiber density was not significantly altered by alcohol in females. Alcohol drinking patterns were similar in both sexes, but males were in a pre-pubertal state for a larger proportion of the alcohol exposure period, which may have contributed to the differential effects on myelinated fiber density. To gain more insight into how alcohol impacts myelinated axons, brain sections from a subset of these animals (n = 6/sex/treatment) were used for microstructural analyses of the nodes of Ranvier. Confocal analysis of nodal domains, flanked by immunofluorescent-labeled contactin-associated protein (Caspr) clusters, indicated that alcohol drinking reduced nodal length-to-width ratios in layers II/III of the Cg1 in both sexes. Despite sex differences in the underlying cause (larger diameter axons after alcohol in males vs. shorter nodal lengths after alcohol in females), reduced nodal ratios could have important implications for the speed and integrity of neural transmission along these axons in both males and females. Alcohol-induced changes to myelinated axonal populations in the Cg1 may contribute to long-lasting changes in prefrontal function associated with early onset drinking.

Clinicopathological characteristics of subtypes of chronic inflammatory demyelinating polyradiculoneuropathy

ObjectiveTo evaluate the clinical and pathological correlations characterising each clinical subtype of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).MethodsWe assessed 106 consecutive patients who had CIDP fulfilling the European Federation of Neurological...

Peripheral Nerve Regeneration Is Independent From Schwann Cell p75NTR Expression.

Schwann cell reprogramming and differentiation are crucial prerequisites for neuronal regeneration and re-myelination to occur following injury to peripheral nerves. The neurotrophin receptor p75NTR has been identified as a positive modulator for Schwann cell myelination during development and implicated in promoting nerve regeneration after injury. However, most studies base this conclusion on results obtained from complete p75NTR knockout mouse models and cannot dissect the specific role of p75NTR expressed by Schwann cells. In this present study, a conditional knockout model selectively deleting p75NTR expression in Schwann cells was generated, where p75NTR expression is replaced with that of an mCherry reporter. Silencing of Schwann cell p75NTR expression was confirmed in the sciatic nerve in vivo and in vitro, without altering axonal expression of p75NTR. No difference in sciatic nerve myelination during development or following sciatic nerve crush injury was observed, as determined by quantification of both myelinated and unmyelinated nerve fiber densities, myelinated axonal diameter and myelin thickness. However, the absence of Schwann cell p75NTR reduced motor nerve conduction velocity after crush injury. Our data indicate that the absence of Schwann cell p75NTR expression in vivo is not critical for axonal regrowth or remyelination following sciatic nerve crush injury, but does play a key role in functional recovery. Overall, this represents the first step in redefining the role of p75NTR in the peripheral nervous system, suggesting that the Schwann cell-axon unit functions as a syncytium, with the previous published involvement of p75NTR in remyelination most likely depending on axonal/neuronal p75NTR and/or mutual glial-axonal interactions.