Evaluation of combined effects of brief electrical stimulation and Schwann-like cells on sciatic nerve injury model.

Severe nerve injuries can be treated with electrical stimulation and stem cell therapies, but little is known about the potential benefits of combining these two treatments. In an effort to investigate this combination, we conducted a study to evaluate the effectiveness of electrical stimulation and Schwann-like cell transplantation in female Wistar albino rats. Our study consisted of five groups of rats: a sham group, an injury group, an electrical stimulation group, a Schwann-like cell group, and a combination group. The experimental groups received electrical stimulation, Schwann-like cell transplantation, or both. The animals sciatic function index was evaluated during a 6-week recovery period, and nerve conduction velocity, wet muscle mass, and nerve tissues were also analyzed. The results of the study showed that all experimental groups had a faster functional recovery compared to the injury group, although the difference between groups was not statistically significant. Both the combination group and the Schwann-like cell transplantation group had a higher nerve conduction velocity compared to the other experimental groups. However, there was no significant difference between the combination and Schwann-like cell transplantation groups. Nonetheless, histological analysis showed a better axonal reorganization in the combination group. The study provides preliminary evidence of the potential benefits of combining electrical stimulation and Schwann-like cell transplantation in treating severe nerve injuries. However, further studies with larger sample sizes are needed to confirm these findings and optimize the treatment parameters.

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

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

Differential effects of rat ADSCs encapsulation in fibrin matrix and combination delivery of BDNF and Gold nanoparticles on peripheral nerve regeneration.

BACKGROUND: Fibrin as an extracellular matrix feature like biocompatibility, creates a favorable environment for proliferation and migration of cells and it can act as a reservoir for storage and release of growth factors in tissue engineering. METHODS: In this study, the inner surface of electrospun poly (lactic-co-glycolic acid) (PLGA) nanofibrous conduit was biofunctionalized with laminin containing brain derived neurotrophic factor (BDNF) and gold nanoparticles in chitosan nanoparticle. The rats were randomly divided into five groups, including autograft group as the positive control, PLGA conduit coated by laminin and filled with DMEM/F12, PLGA conduit coated by laminin and filled with rat-adipose derived stem cells (r-ADSCs), PLGA conduit coated by laminin containing gold-chitosan nanoparticles (AuNPs-CNPs), BDNF-chitosan nanoparticles (BDNF-CNPs) and filled with r-ADSCs or filled with r-ADSCs suspended in fibrin matrix, and they were implanted into a 10 mm rat sciatic nerve gap. Eventually, axonal regeneration and functional recovery were assessed after 12 weeks. RESULTS: After 3 months post-surgery period, the results showed that in the PLGA conduit filled with r-ADSCs without fibrin matrix group, positive effects were obtained as compared to other implanted groups by increasing the sciatic functional index significantly (p < 0.05). In addition, the diameter nerve fibers had a significant difference mean in the PLGA conduit coated by laminin and conduit filled with r-ADSCs in fibrin matrix groups relative to the autograft group (p < 0.001). However, G-ratio and amplitude (AMP) results showed that fibrin matrix might have beneficial effects on nerve regeneration but, immunohistochemistry and real-time RT-PCR outcomes indicated that the implanted conduit which filled with r-ADSCs, with or without BDNF-CNPs and AuNPs-CNPs had significantly higher expression of S100 and MBP markers than other conduit implanted groups (p < 0.05). CONCLUSIONS: It seems, in this study differential effects of fibrin matrix, could be interfered it with other factors thereby and further studies are required to determine the distinctive effects of fibrin matrix combination with other exogenous factors in peripheral nerve regeneration.

Whole-body vibration therapy does not improve the peripheral nerve regeneration in experimental model.

OBJECTIVES: Whole-body vibration (WBV) is commonly used to improve motor function, balance and functional performance, but its effects on the body are not fully understood. The main objective was to evaluate the morphometric and functional effects of WBV in an experimental nerve regeneration model. METHODS: Wistar rats were submitted to unilateral sciatic nerve crush and treated with WBV (4-5 weeks), started at 3 or 10 days after injury. Functional performances were weekly assessed by sciatic functional index, horizontal ladder rung walking and narrow beam tests. Nerve histomorphometry analysis was assessed at the end of the protocol. RESULTS: Injured groups, sedentary and WBV started at 3 days, had similar functional deficits. WBV, regardless of the start time, did not alter the histomorphometry parameters in the regeneration process. CONCLUSIONS: The earlier therapy did not change the expected and natural recovery after the nerve lesion, but when the WBV starts later it seems to impair function parameter of recovery.

Toll-Like Receptor 9-Mediated Neuronal Innate Immune Reaction Is Associated with Initiating a Pro-Regenerative State in Neurons of the Dorsal Root Ganglia Non-Associated with Sciatic Nerve Lesion.

One of the changes brought about by Wallerian degeneration distal to nerve injury is disintegration of axonal mitochondria and consequent leakage of mitochondrial DNA (mtDNA)-the natural ligand for the toll-like receptor 9 (TLR9). RT-PCR and immunohistochemical or Western blot analyses were used to detect TLR9 mRNA and protein respectively in the lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) ipsilateral and contralateral to a sterile unilateral sciatic nerve compression or transection. The unilateral sciatic nerve lesions led to bilateral increases in levels of both TLR9 mRNA and protein not only in the lumbar but also in the remote cervical DRG compared with naive or sham-operated controls. This upregulation of TLR9 was linked to activation of the Nuclear Factor kappa B (NFκB) and nuclear translocation of the Signal Transducer and Activator of Transcription 3 (STAT3), implying innate neuronal immune reaction and a pro-regenerative state in uninjured primary sensory neurons of the cervical DRG. The relationship of TLR9 to the induction of a pro-regenerative state in the cervical DRG neurons was confirmed by the shorter lengths of regenerated axons distal to ulnar nerve crush following a previous sciatic nerve lesion and intrathecal chloroquine injection compared with control rats. The results suggest that a systemic innate immune reaction not only triggers the regenerative state of axotomized DRG neurons but also induces a pro-regenerative state further along the neural axis after unilateral nerve injury.

Polyethylene glycol-fusion repair of sciatic allografts in female rats achieves immunotolerance via attenuated innate and adaptive responses.

Ablation/segmental loss peripheral nerve injuries (PNIs) exhibit poor functional recovery due to slow and inaccurate outgrowth of regenerating axons. Viable peripheral nerve allografts (PNAs) as growth-guide conduits are immunologically rejected and all anucleated donor/host axonal segments undergo Wallerian degeneration. In contrast, we report that ablation-type sciatic PNIs repaired by neurorrhaphy of viable sciatic PNAs and a polyethylene glycol (PEG)-fusion protocol using PEG immediately restored axonal continuity for many axons, reinnervated/maintained their neuromuscular junctions, and prevented much Wallerian degeneration. PEG-fused PNAs permanently restored many sciatic-mediated behaviors within 2-6 weeks. PEG-fused PNAs were not rejected even though host/donors were neither immunosuppressed nor tissue-matched in outbred female Sprague Dawley rats. Innate and adaptive immune responses to PEG-fused sciatic PNAs were analyzed using electron microscopy, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction for morphological features, T cell and macrophage infiltration, major histocompatibility complex (MHC) expression, apoptosis, expression of cytokines, chemokines, and cytotoxic effectors. PEG-fused PNAs exhibited attenuated innate and adaptive immune responses by 14-21 days postoperatively, as evidenced by (a) many axons and cells remaining viable, (b) significantly reduced infiltration of cytotoxic and total T cells and macrophages, (c) significantly reduced expression of inflammatory cytokines, chemokines, and MHC proteins, (d) consistently low apoptotic response. Morphologically and/or biochemically, PEG-fused sciatic PNAs often resembled sciatic autografts or intact sciatic nerves. In brief, PEG-fused PNAs are an unstudied, perhaps unique, example of immune tolerance of viable allograft tissue in a nonimmune-privileged environment and could greatly improve the clinical outcomes for PNIs relative to current protocols.

Transplantation of Mesenchymal Stromal Cells Expressing the Human Preproenkephalin Gene Can Relieve Pain in a Rat Model of Neuropathic Pain.

Transgenic therapy for central neuralgia faces the problems of low expression and weak targeting and affects superficial but not deep neurons. In this study, we generated a lentivirus vector with human preproenkephalin gene (hPPE) expression driven by the transcriptional amplification strategy system (TAS) and established a primary bone marrow-derived mesenchymal stromal cell (BMSC) line stably expressing hPPE for transplantation into a rat model of neuropathic pain rat. The paw thermal withdrawal latency assay and paw mechanical withdrawal threshold assay showed that unlike control BMSCs and BMSCs with hPPE overexpression driven by the CMV or Synapsin 1 (SYN1) promoter, TAS-hPPE BMSCs had a robust and lasting analgesic effect. The TAS-hPPE BMSC-treated group exhibited higher expression of TAS-driven hPPE and a higher ratio of BMSCs in the midbrain, spinal cord and cortex then the CMV-hPPE BMSC- and SYN1-hPPE BMSC-treated groups. Moreover, we also observed that TAS-hPPE BMSCs displayed a greater tendency to differentiate into neurons and exhibit neuronal-like distribution than CMV-hPPE or SYN1-hPPE BMSCs. In conclusion, our study shows that the TAS improves BMSC transgenic therapy for neuropathic pain treatment.

Magnetic resonance imaging of enhanced nerve repair with mesenchymal stem cells combined with microenvironment immunomodulation in neurotmesis.

INTRODUCTION: The immuno-microenvironment of injured nerves adversely affects mesenchymal stem cell (MSC) therapy for neurotmesis. Magnetic resonance imaging (MRI) can be used noninvasively to monitor nerve degeneration and regeneration. The aim of this study was to investigate nerve repair after MSC transplantation combined with microenvironment immunomodulation in neurotmesis by using multiparametric MRI. METHODS: Rats with sciatic nerve transection and surgical coaptation were treated with MSCs combined with immunomodulation or MSCs alone. Serial multiparametric MRI examinations were performed over an 8-week period after surgery. RESULTS: Nerves treated with MSCs combined with immunomodulation showed better functional recovery, rapid recovery of nerve T2, fractional anisotropy and radial diffusivity values, and more rapid restoration of the fiber tracks than nerves treated with MSCs alone. DISCUSSION: Transplantation of MSCs in combination with immunomodulation can exert a synergistic repair effect on neurotmesis, which can be monitored by multiparametric MRI.

Differentiated adipose-derived stem cells promote peripheral nerve regeneration.

INTRODUCTION: Many reports have indicated that adipose-derived stem cells (ADSCs) are effective for nerve regeneration. We investigated nerve regeneration by combining a polyglycolic acid collagen (PGA-c) tube, which is approved for clinical use, and Schwann cell-like differentiated ADSCs (dADSCs). METHODS: Fifteen-millimeter-long gaps in the sciatic nerve of rats were bridged in each group using tubes (group I), with tubes injected with dADSCs (group II), or by resected nerve (group III). RESULTS: Axonal outgrowth was greater in group II than in group I. Tibialis anterior muscle weight revealed recovery only in group III. Latency in nerve conduction studies was equivalent in group II and III, but action potential was lower in group II. Transplanted dADSCs maintained Schwann cell marker expression. ATF3 expression level in the dorsal root ganglia was equivalent in groups II and III. DISCUSSION: dADSCs maintained their differentiated state in the tubes and are believed to have contributed to nerve regeneration.

GABAergic cell transplants in the anterior cingulate cortex reduce neuropathic pain aversiveness.

Dysfunction of inhibitory circuits in the rostral anterior cingulate cortex underlies the affective (aversive), but not the sensory-discriminative features (hypersensitivity) of the pain experience. To restore inhibitory controls, we transplanted inhibitory interneuron progenitor cells into the rostral anterior cingulate cortex in a chemotherapy-induced neuropathic pain model. The transplants integrated, exerted a GABA-A mediated inhibition of host pyramidal cells and blocked gabapentin preference (i.e. relieved ongoing pain) in a conditioned place preference paradigm. Surprisingly, pain aversiveness persisted when the transplants populated both the rostral and posterior anterior cingulate cortex. We conclude that selective and long lasting inhibition of the rostral anterior cingulate cortex, in the mouse, has a profound pain relieving effect against nerve injury-induced neuropathic pain. However, the interplay between the rostral and posterior anterior cingulate cortices must be considered when examining circuits that influence ongoing pain and pain aversiveness.

Pediatric sciatic neuropathy: Clinical presentation and long term follow up. / Neuropatía ciática en pediatría: Presentación clínica y seguimiento a largo plazo.

INTRODUCTION: Sciatic neuropathy is rare and difficult to diagnose in pediatrics, and its long-term course has not been completely understood. OBJECTIVE: To analyze the clinical presentation and evolution of a group of pediatric patients with sciatic neuropathy. PATIENTS AND METHOD: Retrospective anal ysis of the clinical characteristics of pediatric patients with sciatic neuropathy treated in two hospitals of Santiago between 2014 and 2018. Locomotor examination, muscle trophism, deep tendon reflexes, gait, sensation, and pain were assessed. Sciatic nerve conduction study and electromyography (EMG) were performed, and magnetic resonance imaging (MRI) in three patients. RESULTS: Six patients were included with an average age of 11.8 years. The etiologies were traumatic (N = 2), by compression (N = 2), vascular (N = 1), and tumor (N = 1). All of the 6 patients presented foot drop and Achilles tendon hyporeflexia/areflexia, and 5 patients presented severe neuropathic pain. The EMG showed involvement of the sciatic nerve rami and dependent muscles. In two patients, a pelvic girdle and lower limbs MRI was performed, showing selective muscle involvement in sciatic territory. One patient underwent a lumbosacral plexus MRI, and subsequently histological study showing a benign neural tumor. Out of the three patients who were followed-up longer than one year presented motor sequelae and gait disorder. CONCLUSION: Sciatic neuropathy in the study group was secondary to different causes, predominantly traumatic and compressive etiologies. The three patients that were ina long-term follow-up presented significant motor sequelae. In most of the cases, neural injury wasassoci- ated with preventable causes, such as accidents and positioning in unconscious children, which is crucial in the prevention of a pathology with a high sequelae degree.

Synergistic Effects of Acetyl-l-Carnitine and Adipose-Derived Stromal Cells on Improving Regenerative Capacity of Acellular Nerve Allograft in Sciatic Nerve Defect.

The combination of decellularized nerve allograft and adipose-derived stromal cells (ASCs) represents a good alternative to nerve autograft for bridging peripheral nerve defects by providing physical guidance and biologic cues. However, the regeneration outcome of acellular nerve allograft (ANA) is often inferior to autograft. Therefore, we hypothesized that acetyl-l-carnitine (ALCAR) treatment and implantation of ASC-embedded ANA would work synergistically to promote nerve regeneration. Seventy rats were randomly allocated into seven experimental groups (n = 10), including the healthy control group, sham surgery group, autograft group, ANA group, ANA + ASCs group, ANA + ALCAR group (50 mg/kg for 2 weeks), and ANA + ASCs + ALCAR (50 mg/kg for 2 weeks) group. All grafts were implanted to bridge long-gap (10-mm) sciatic nerve defects. Functional, electrophysiological, and morphologic analysis was conducted during the experimental period. We found that ALCAR potentiated the survival and retention of transplanted ASCs and upregulated the expression of neurotrophic factor mRNAs in transplanted grafts. Sixteen weeks following implantation in the rat, the ANA supplemented by ASCs was capable of supporting reinnervation across a 10-mm sciatic nerve gap, with results close to that of the autografts in terms of functional, electrophysiological, and histologic assessments. Results demonstrated that ALCAR treatment improved regenerative effects of ANA combined with ASCs on reconstruction of a 10-mm sciatic nerve defect in rat comparable to those of autograft.

Crush injury to motor nerves in the G93A transgenic mouse model of amyotrophic lateral sclerosis promotes muscle reinnervation and survival of functionally intact nerve-muscle contacts.

Selective survival of small motor nerve fibers and their neuromuscular contacts in the SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis (ALS) suggests that smaller regenerated nerve fibers are more able to sustain reformed nerve-muscle connections as functionally intact motor units (MUs). The sciatic nerve was crushed unilaterally in SOD1G93A transgenic mice at 40 days of age and contractile forces of reinnervated muscles and their MUs were recorded at 90 days in order to determine the capacities of the nerves to regenerate and to form and retain functional neuromuscular connections. Reduced MU numbers in fast-twitch tibialis anterior, extensor digitorum longus and medial gastrocnemius muscles and the lesser reductions in slow-twitch soleus muscle of SOD1G93A transgenic mice were reversed in reinnervated muscles: there were more reinnervated MUs and their contractile forces and the muscle forces and weights increased. In line with the contrasting ability of only small not large nerve fibers to sprout to form enlarged MUs in the SOD1G93A transgenic mouse, the smaller regenerating nerve fibers formed enlarged MUs that were better able to survive. Because nerve fibers with and without muscle contacts were severed by the sciatic nerve crush injury, the conditioning lesion is untenable as the explanation for improved maintenance of reinnervated neuromuscular junctions. Elevated neurotrophic factor expression in axotomized motoneurons and/or denervated Schwann cells and the synapse withdrawal from axotomized motoneurons are other factors that, in addition to reduced size of nerve fibers reinnervating muscles, may account for increased survival and size of reinnervated MUs in ALS.

Polyethylene glycol treated allografts not tissue matched nor immunosuppressed rapidly repair sciatic nerve gaps, maintain neuromuscular functions, and restore voluntary behaviors in female rats.

Many publications report that ablations of segments of peripheral nerves produce the following unfortunate results: (1) Immediate loss of sensory signaling and motor control; (2) rapid Wallerian degeneration of severed distal axons within days; (3) muscle atrophy within weeks; (4) poor behavioral (functional) recovery after many months, if ever, by slowly-regenerating (∼1mm/d) axon outgrowths from surviving proximal nerve stumps; and (5) Nerve allografts to repair gap injuries are rejected, often even if tissue matched and immunosuppressed. In contrast, using a female rat sciatic nerve model system, we report that neurorrhaphy of allografts plus a well-specified-sequence of solutions (one containing polyethylene glycol: PEG) successfully addresses each of these problems by: (a) Reestablishing axonal continuity/signaling within minutes by nonspecific ally PEG-fusing (connecting) severed motor and sensory axons across each anastomosis; (b) preventing Wallerian degeneration by maintaining many distal segments of inappropriately-reconnected, PEG-fused axons that continuously activate nerve-muscle junctions; (c) maintaining innervation of muscle fibers that undergo much less atrophy than otherwise-denervated muscle fibers; (d) inducing remarkable behavioral recovery to near-unoperated levels within days to weeks, almost certainly by CNS and PNS plasticities well-beyond what most neuroscientists currently imagine; and (e) preventing rejection of PEG-fused donor nerve allografts with no tissue matching or immunosuppression. Similar behavioral results are produced by PEG-fused autografts. All results for Negative Control allografts agree with current neuroscience data 1-5 given above. Hence, PEG-fusion of allografts for repair of ablated peripheral nerve segments expand on previous observations in single-cut injuries, provoke reconsideration of some current neuroscience dogma, and further extend the potential of PEG-fusion in clinical practice.

Delivery of adipose-derived stem cells in poloxamer hydrogel improves peripheral nerve regeneration.

INTRODUCTION: Peripheral nerve damage is associated with high long-term morbidity. Because of beneficial secretome, immunomodulatory effects, and ease of clinical translation, transplantation with adipose-derived stem cells (ASC) represents a promising therapeutic modality. METHODS: Effect of ASC delivery in poloxamer hydrogel was assessed in a rat sciatic nerve model of critical-sized (1.5 cm) peripheral nerve injury. Nerve/muscle unit regeneration was assessed via immunostaining explanted nerve, quantitative polymerase chain reaction (qPCR), and histological analysis of reinnervating gastrocnemius muscle. RESULTS: On the basis of viability data, 10% poloxamer hydrogel was selected for in vivo study. Six weeks after transection and repair, the group treated with poloxamer delivered ASCs demonstrated longest axonal regrowth. The qPCR results indicated that the inclusion of ASCs appeared to result in expression of factors that aid in reinnervating muscle tissue. DISCUSSION: Delivery of ASCs in poloxamer addresses multiple facets of the complexity of nerve/muscle unit regeneration, representing a promising avenue for further study. Muscle Nerve 58: 251-260, 2018.

Delayed sciatic nerve compression following hamstring injury.

A 47-year-old man presented three months post-hamstring injury with posterior thigh and buttock pain, paraesthesia over the lateral part of the leg and dorsum of the foot and a foot drop. MRI identified a hamstring muscle injury with a lesion surrounding 20 cm of the proximal sciatic nerve consistent with an extensive haematoma. Surgical debridement and release was planned; however, his signs spontaneously resolved with rest, physiotherapy and splintage prior to surgery. There have been no other reports of a sciatic nerve lesion with neurological signs resolving without surgical exploration.

Serial assessment of functional recovery following nerve injury using implantable thin-film wireless nerve stimulators.

INTRODUCTION: Comprehensive assessment of the time course of functional recovery following peripheral nerve repair is critical for surgical management of peripheral nerve injuries. This study describes the design and implementation of a novel implantable wireless nerve stimulator capable of repeatedly interfacing peripheral nerve tissue and providing serial evaluation of functional recovery postoperatively. METHODS: Thin-film wireless implants were fabricated and subcutaneously implanted into Lewis rats. Wireless implants were used to serially stimulate rat sciatic nerve and assess functional recovery over 3 months following various nerve injuries. RESULTS: Wireless stimulators demonstrated consistent performances over 3 months in vivo and successfully facilitated serial assessment of nerve and muscle function following nerve crush and nerve transection injuries. CONCLUSIONS: This study highlights the ability of implantable wireless nerve stimulators to provide a unique view into the time course of functional recovery in multiple motor targets. Muscle Nerve 54: 1114-1119, 2016.

MicroRNA-338 and microRNA-21 co-transfection for the treatment of rat sciatic nerve injury.

The objective of this study is to find if co-transfecting microRNA-338 and microRNA-21 into the neurons in the spinal cord can promote functional recovery after peripheral nerve injury in rats. Animals were divided into three groups: 20 animals in the GFP control vector group (group A), 20 animals in the GFP experimental vector group (group B) and ten animals in the normal control group. Right sciatic nerves of animals in groups A and B were transected and were bridged with collagen nerve conduits with 10 mm distance between the stumps. 3 µl GFP control vector or 3 µl lentiviral vectors encoding the sequence of microRNA-338 and microRNA-21 were injected in the conduit. 8 weeks after the surgery, the treatment effect was evaluated by functional analysis, electrophysiological analysis, immunohistochemical analysis as well as transmitting electronic microscope observations in all the rats. Animals treated with microRNA-338 and microRNA-21 showed significantly better recovery than GFP control group animals by means of functional analysis (Sciatic nerve index -47.7 ± 2.5 vs -59.4 ± 3.7), electrophysiological analysis (Conduction velocity 20.5 ± 2.8 vs 10.5 ± 1.4 m/s), ratio of wet weight of the gastrocnemius muscles (0.83 ± 0.03 vs 0.55 ± 0.06), axon diameter (5.0 ± 1.8 µm vs 4.0 ± 2.2), myelin sheath thickness (1.4 ± 0.43 vs 0.80 ± 0.31 µm) and G-ratio (0.80 ± 0.06 vs 0.75 ± 0.04). Lentiviral vectors encoding microRNA 338 and 21 might be explored in the future as potential therapeutic intervention to promote nerve regeneration.

Properties of the tibialis anterior muscle after treatment with laser therapy and natural latex protein following sciatic nerve crush.

INTRODUCTION: In this study we evaluated the characteristics of the tibialis anterior muscle after sciatic nerve crush and treatment with low-level laser therapy (LLLT) or the protein from natural latex (P1). METHODS: We studied the following 6 groups of male Wistar rats: control (CG); exposed nerve (EG); injured nerve (IG); injured nerve with LLLT (LG); injured nerve with P1 (PG); and injured nerve with P1 and LLLT (LPG). RESULTS: After 4 weeks, muscle morphology showed improvement in the treated groups; after 8 weeks, the treated groups resembled controls, especially the PG. Morphometry revealed muscle fiber atrophy after nerve injury, with time-dependent recovery. Histochemical analysis revealed increased intermediate fiber area. The PG was more similar to controls with NADH staining, whereas the LPG more closely resembled controls with SDH staining. CONCLUSION: Treatment using only P1 proved most efficient, revealing a negative interaction between P1 and LLLT.

Electrical stimulation influences satellite cell differentiation after sciatic nerve crush injury in rats.

INTRODUCTION: Electrical stimulation is often used to prevent muscle atrophy and preserve contractile function, but its effects on the satellite cell population after nerve injury are not well understood. In this study we aimed to determine whether satellite cell differentiation is affected by electrical stimulation after nerve crush. METHODS: The sciatic nerves of Sprague-Dawley (SD) rats were crushed. Half of the injured rats received daily electrical stimulation of the gastrocnemius muscle, and the others did not. Tests for detecting paired box protein 7 (Pax7), myogenic differentiation antigen (MyoD), embryonic myosin heavy chain (eMyHC), and force production were performed 2, 4, and 6 weeks after injury. RESULTS: More Pax7+/MyoD+ nuclei in stimulated muscles were observed than in non-stimulated muscles. eMyHC expression was elevated in stimulated muscles and correlated positively with enhanced force production. CONCLUSIONS: Increased satellite cell differentiation is correlated with preserved muscle function in response to electrical stimulation after nerve injury.