Peripheral Neural System Research Articles

PC12 differentiation to neuron cells activated by a low-level laser at 660 nm on UV pre-treated CR-39 scaffolds with parallel microchannels.

The lack of regeneration of injured neurons in the central and peripheral neural system leads to the failure of damaged tissue repair in patients. While there is no definitive cure for most neurodegenerative diseases, new therapeutic methods that cause the proliferation and differentiation of neurons are of interest. Challenges such as the inability of neuronal cells to proliferate after injury, the lack of a stimulus for initial stimulation, and the presence of the microenvironment around CNS neurons contain several inhibitory factors that prevent neuron regeneration, thus, creating a structure similar to the extracellular matrix helps the cell proliferation in current treatment. A rapid method of neuron-like cell differentiation of PC12 cells is introduced here based on a novel synthetic scaffold. Initially, poly allyldiglycol carbonate (CR-39) substrate is textured under a high dose of ArF UV excimer laser (1000 shot, 300 mJ/pulse equivalent to 300 J/cm2 at 193 nm) to create superficial periodic parallel microchannels with the micrometer spacing and sub-micron width. Ultraviolet treated CR-39 (UT CR-39) provides a suitable scaffold to speed up the transformation/differentiation of PC12 cells. The latter is pheochromocytoma of the rat adrenal medulla as an embryonic origin from the neural crest usually exposed to the nerve growth factor (NGF). In fact, PC12 cells are seeded on the microchannels and simultaneously are stimulated by coherent red photons at 660 nm within the therapeutic window. The UT CR-39 scaffold undergoes extra improvement of ∼ 30% after 12 minutes of laser activation regarding the photo-biomodulation (PBM) mechanism. The cell activation due to the coherent photons also gives rise to enhanced proliferation/differentiation. Here, PC12 cells are efficiently differentiated into neurons according to immunocytochemistry (ICC) and Western Blot verification tests based on MAP2 and synapsin-1 protein expression. In general, UT CR-39 acts as a superior bed to elevate the population of neuron-like cells up to threefold against those of untreated (control)ones. We conclude that the surface cross-linking due to UV exposure and subsequent induced hydrophilicity notably contribute to the neuron-like cell differentiation of PC12 without adding NGF.

Unraveling the Connection: Pancreatic Cancer Cells and Schwann Cells.

Pancreatic ductal adenocarcinoma is one of the most lethal solid malignancies, characterized by its aggressiveness and metastatic potential, with a 5-year survival rate of only 13%. Progress in the management of metastatic disease has been modest. A robust connection between nervous system and tumor progression exists, with prominent neural alterations having been observed during pancreatic cancer's progression, including neural hypertrophy, neural density, and neural remodeling. The pancreatic tumor microenvironment includes s set of cells and structures that constantly dialogue with cancer cells, influencing its growth and behavior. The microglia is key cellular components of the tumor microenvironment, and Schwann cells are the principal glial cells in the peripheral neural system. Schwann cells can regulate changes in the tumor microenvironment and immune responses by secreting a variety of factors and can support a tumor's invasion of nerves and distant metastasis, with further pain exacerbation. Schwann cells secrete various pain-related molecules, such as the neural growth factor, to mediate the activation of primary sensory neurons, leading to pain induction. The binding of the neural growth factor to tropomyosin receptor kinase A is an important signaling mechanism for pain perception in humans. Consequently, directing efforts towards targeting neural invasion may provide an alternative strategy to improve the prognosis of and alleviate pain in patients with pancreatic cancer.

The Possibility of Improvement in Balance and Function Following Conjunct Effects of Transcranial Direct Current Stimulation and Whole-Body Vibration Therapy in Spastic Cerebral Palsy Patients: A Hypothesis Study

Cerebral palsy (CP) results from developmental brain injury, affecting posture and muscular coordination. Traditional treatments offer varying effectiveness, among them the most recent therapies are whole-body vibration therapy (WBVT) and transcranial direct current stimulation (tDCS). WBV enhances proprioceptive function, muscle mass, bone density, and joint stability by stimulating muscle spindle fibers and activating dormant motor units. It also modulates spastic reflexes through mechanoreceptors, proving more effective than traditional physiotherapy. tDCS, a non-invasive neuromodulation, reshapes cortical excitability and modulates synaptic plasticity by altering neuronal activity. It affects long-term potentiation and depression, crucial in learning and adaptive functions. tDCS's interaction with neurotransmitters, especially dopamine and GABA, and its effect on NMDA and dopaminergic receptors make it promising for CP rehabilitation. Both therapies offer novel insights into CP rehabilitation through their influence on central and peripheral neural system. This hypothesis study tends to explore the conjunct effects of transcranial direct current stimulation (tDCS) and whole-body vibration therapy (WBVT) on improving balance and function in children with spastic cerebral palsy. The hypothesis suggests that WBVT's vibratory input, alongside tDCS's central stimulation, enhances function by modulating neuronal excitability and sensory information. The tonic vibration reflex (TVR) from WBV is believed to amplify muscle strength and modulate spinal excitability. When integrated with tDCS, it might accelerate excitability in the motor cortex, essential for brain-injured patient rehabilitation. Despite evidence of individual benefits from both therapies, conjunct effects remain under-researched. Preliminary results show improvements in balance, gait velocity, and motor functions. Validating this combined approach could revolutionize treatment for children with spastic cerebral palsy.

Research progress of acupuncture mediated analgesia via regulating the function of endocannabinoid system

Endocannabinoid system (ECS), which composed of its ligands and receptors, widely distributes in peripheral tissues and nerve system. Through complex regulating mechanisms, ECS exerts a variety of biological functions including analgesia. Its utility in analgesic regulation has attracted extensive attention, and the related achievements have also been transformed into clinical practice. With the deepened understanding of the essence of pain, as well as the advances in research techniques, quantity of research evidences showed that ECS could be regulated by acupuncture treatment and exerted analgesic effect in inflammatory pain, neuropathic pain and other related diseases, and the mechanism had also been revealed gradually. By reviewing literatures related to acupuncture analgesia and ECS, we summarized the effect and mechanism of acupuncture analgesia involved with regulation of ECS, pointed out cannabinoid (CB) 1 receptor and CB2 receptor exerted analgesic effect in central and peripheral neural system through mechanisms of inhibiting neural activation and anti-inflammation, respectively. Therefore, we hope to provide reference and inspiration for relevant research and clinical practice in the future.

Regulators of angiogenesis in chemotherapy-induced peripheral neuropathy

Background: Chemotherapy-induced peripheral polyneuropathy is a major neurotoxicity of treatment for acute lymphoblastic leukemia (ALL) in children. Pathophysiological mechanisms of the injury of peripheral neural system are not fully investigated; however, some studies have shown the involvement of vascular endothelial growth factors.
 Aim: To evaluate plasma levels of angiogenic growth factors in children with ALL and to identify their association with the development of vincristine-induced peripheral polyneuropathy.
 Materials and methods: This single center prospective study included 41 patients with ALL aged 3 to 17 years. All patients were given the ALL-MB 2015 chemotherapy regimen. Depending on the vincristine-induced peripheral polyneuropathy, the patients were divided into two groups: the main group (n = 22) comprised of the patients with neurological signs and symptoms of peripheral neuropathy and the control group (n = 19), those without clinical signs of the peripheral nervous system involvement. The levels of angiogenic growth factors (VEGF-A, VEGF-D, PlGF-1, and PDGF-BB) were measured in plasma by multiparameter immunofluorescent analysis.
 Results: During 3 months of the follow up the chemotherapy-induced signs of peripheral polyneuropathy developed in 53.6% (n = 22) of the children. In 72.7% (n = 16) of the patients the chemotherapy-induced peripheral polyneuropathy was characterized by a combination of neurologic abnormalities with prevailing motor symptoms. The comparative analysis of plasma angiogenic growth factors in children with ALL depending on the presence or absence of the vincristine-induced peripheral polyneuropathy showed that there was a significant decrease of the VEGF-A in those with chemotherapy-induced peripheral polyneuropathy, compared to those without (Me [Q1; Q3]: 178.20 [138.40; 228.45] and 558.50 [160.10; 650.0], respectively, p 0.017). This parameter had diagnostic sensitivity of 77.7% and specificity of 76.9%.
 Conclusion: We have shown a high clinical value of plasma vascular endothelial growth factor (VEGF-A) level, which makes it possible to consider it as a significant biological marker of neurotoxicity in vincristine-induced peripheral polyneuropathy.

856 Peripheral neuropathic changes in prurigo nodularis

Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intensely pruritic and hyperkeratotic nodules of unknown etiology. PN is strongly associated with peripheral neuropathies, suggesting a role for neural dysregulation in its pathogenesis. Here we study components of the cutaneous peripheral neural system, including intraepidermal nerve fiber density (IENFD), mechanoreceptors, and blood vessels in lesional and nonlesional skin of 10 patients with PN and 10 matched healthy controls.

Hoffmann Reflex Measured From Lateral Gastrocnemius Is More Reliable Than From Soleus Among Elderly With Peripheral Neuropathy.

IntroductionPeripheral neuropathy (PN) affects up to 20% of the population over the age of 60. Hoffmann reflex (H-reflex) may assess PN adaptation by measuring the function of the peripheral neural system and central nervous system (CNS) modulation. This project aimed to find a reliable muscle among triceps surae muscles during standing and walking among the PN population.Materials and MethodsSixteen older adults (> 65 years of age) diagnosed with PN were recruited in this study. The H-reflex test was conducted on the muscle belly of the soleus (SOL), the medial (MG), and lateral gastrocnemius (LG) during standing and walking (heel contact, midstance, and toe-off phases). All measurements were collected on two occasions, separated by at least 7 days. Intraclass correlation coefficients (ICCs) and their confidence intervals (CIs) were used to examine the consistency of the H-reflex outcome variables in the repeated tests for all three tested muscles.ResultsThe ICCs of H-index during standing and the three walking phases were poor to moderate in SOL (0.486∼0.737) and MG (0.221∼0.768), and moderate to high in LG (0.713∼0.871). The ICCs of H/M ratio were poor to moderate in SOL (0.263∼0.702) and MG (0.220∼0.733), and high in LG (0.856∼0.958).ConclusionThe H-reflex of LG was more reliable than SOL and MG during standing and walking among older adults with peripheral neuropathy. It is crucial for future studies in this population to study H-reflex of LG, not SOL and MG, for more reliable results.

Graded motor imagery modifies movement pain, cortical excitability and sensorimotor function in complex regional pain syndrome.

Patients with complex regional pain syndrome suffer from chronic neuropathic pain and also show a decrease in sensorimotor performance associated with characteristic central and peripheral neural system parameters. In the brain imaging domain, these comprise altered functional sensorimotor representation for the affected hand side. With regard to neurophysiology, a decrease in intracortical inhibition for the sensorimotor cortex contralateral to the affected hand has been repetitively verified, which might be related to increased primary somatosensory cortex functional activation for the affected limb. Rare longitudinal intervention studies in randomized controlled trials have demonstrated that a decrease in primary somatosensory cortex functional MRI activation coincided with pain relief and recovery in sensorimotor performance. By applying a randomized wait-list control crossover study design, we tested possible associations of clinical, imaging and neurophysiology parameters in 21 patients with complex regional pain syndrome in the chronic stage (>6 months). In more detail, we applied graded motor imagery over 6 weeks to relieve movement pain of the affected upper limb. First, baseline parameters were tested between the affected and the non-affected upper limb side and age-matched healthy controls. Second, longitudinal changes in clinical and testing parameters were associated with neurophysiological and imaging parameters. During baseline short intracortical inhibition, as assessed with transcranial magnetic stimulation, was decreased only for hand muscles of the affected hand side. During movement of the affected limb, primary somatosensory cortex functional MRI activation was increased. Hand representation area size for somatosensory stimulation in functional MRI was smaller on the affected side with longer disease duration. Graded motor imagery intervention but not waiting, resulted in a decrease of movement pain. An increase of somatosensory hand representation size over graded motor imagery intervention was related to movement pain relief. Over graded motor imagery intervention, pathological parameters like the increased primary somatosensory cortex activation during fist movement or decreased short intracortical inhibition were modified in the same way as movement pain and hand performance improved. No such changes were observed during the waiting period. Overall, we demonstrated characteristic changes in clinical, behaviour and neuropathology parameters applying graded motor imagery in patients with upper limb complex regional pain syndrome, which casts light on the effects of graded motor imagery intervention on biomarkers for chronic neuropathic pain.

An Artificial Peripheral Neural System Based on Highly Stretchable and Integrated Multifunctional Sensors

AbstractProstheses and robots have been affecting all aspects of life. Making them conscious and intelligent like humans is appealing and exciting, while there is a huge contrast between progress and strong demand. An alternative strategy is to develop an artificial peripheral neural system with high‐performance bionic receptors. Here, a novel functional composite material that can serve as a key ingredient to simultaneously construct different artificial exteroceptive sensors (AE sensors) and artificial proprioceptive sensors (AP sensors) is demonstrated. Both AP sensors and AE sensors demonstrate outstandingly high stretchability; up to 200% stretching strain and possess the superior performance of fast response and high stability. An artificial peripheral neural system integrated with the highly stretchable AP sensor and AE sensor is constructed, which makes a significant breakthrough in the perception foundation of efficient proprioception and exteroception for intelligent prostheses and soft robots. Accurate feedback on the activities of body parts, music control, game manipulation, and wireless typing manifest the enormous superiority of the spatiotemporal resolution function of the artificial peripheral neural system, all of which powerfully contribute to promoting intelligent prostheses and soft robots into sophistication, and are expected to make lives more fascinating.

Neuromodulatory effect of GnRH from coeliac ganglion on luteal regression in the late pregnant rat.

The GnRH/GnRH receptor system has been found in several extrapituitary tissues, although its physiological significance has not yet been well established. Taking into account that the peripheral neural system can act as a modulator of pregnancy corpus luteum, the objective was to physiologically investigate the presence of the GnRH system in coeliac ganglion (CG) and to analyse its possible involvement in luteal regression through the superior ovarian nerve (SON) at the end of pregnancy in the rat. The integrated ex vivo CG-SON-Ovary system of rats on day 21 of pregnancy was used. Cetrorelix (CTX), a GnRH receptor antagonist, was added into the ganglionic compartment while the control systems were untreated. Ganglionic GnRH release was detected under basal conditions. Then, the CTX addition in CG increased it, which would indicate the blockade of the receptor. In turn, CTX in CG caused an increase in ovarian progesterone release. Furthermore, the luteal cells showed an increase in the expression of Hsd3b1 and a decrease in the expression of Akr1c3 (progesterone synthesis and degradation enzymes, respectively), reduced TUNEL staining according to an increase in the antioxidant defence system activity and low lipid peroxide levels. The ovarian and ganglionic nitric oxide (NO) release increased, while the luteal nitrotyrosine content, measured as nitrosative stress marker, decreased. CTX in CG decreased the ovarian noradrenaline release. The present study provides evidence that GnRH from CG may trigger neuronal signals that promote the luteal regression in late pregnancy by affecting the release of NO and noradrenaline in the ovary.

Disease Associated Mutations in KIR Proteins Linked to Aberrant Inward Rectifier Channel Trafficking.

The ubiquitously expressed family of inward rectifier potassium (KIR) channels, encoded by KCNJ genes, is primarily involved in cell excitability and potassium homeostasis. Channel mutations associate with a variety of severe human diseases and syndromes, affecting many organ systems including the central and peripheral neural system, heart, kidney, pancreas, and skeletal muscle. A number of mutations associate with altered ion channel expression at the plasma membrane, which might result from defective channel trafficking. Trafficking involves cellular processes that transport ion channels to and from their place of function. By alignment of all KIR channels, and depicting the trafficking associated mutations, three mutational hotspots were identified. One localized in the transmembrane-domain 1 and immediately adjacent sequences, one was found in the G-loop and Golgi-export domain, and the third one was detected at the immunoglobulin-like domain. Surprisingly, only few mutations were observed in experimentally determined Endoplasmic Reticulum (ER)exit-, export-, or ER-retention motifs. Structural mapping of the trafficking defect causing mutations provided a 3D framework, which indicates that trafficking deficient mutations form clusters. These “mutation clusters” affect trafficking by different mechanisms, including protein stability.

The role of Zi2 during neural tube and neural crest development

The transcription factor Zic2 is member of Zic family, at early stages it has been involved in several processes during embryonic development and later on in morphogenesis and organogenesis. An important role has been attributed to Zic2 during the development of the neural system. It has been involved in neural tube and neural crest formation. Both process structures will form the central and peripheral neural system. Mutation of Zic2 provokes holoprosencephaly in humans and in mouse also spina bifida. To date, there is not well elaborated the specific mechanisms under which Zic2 affect neural tube formation and the differences may exist between mouse and human phenotype. Almost the same ambiguity is for the specific role of Zic2 during neural crest development. Here is given are resumed latest studies and are given new insight about the role of Zic2 in these two processes and its new target genes.

Differentiating overlapping symptoms of vulvodynia and pudendal neuralgia.

Vulvodynia is defined as a chronic vulvar pain non-associated with infectious, inflammatory, neoplastic or hormonal disorders. To present a case demonstrating the difficulty in assessing concomitant disease in vulvodynia. A 26-year-old woman, presented with persistent vulvodynia. She received oral and topical medications and behavioural interventions to lessen sexual pain and restore sexuality. As sexual pain decreased, the patient reported symptoms previously not mentioned: continuous, intense periclitoral pain and numbness at the perineum when sitting for a long time. These new symptoms suggest the involvement of the peripheral neural system. The physical evaluation confirmed right-side pelvic distortion, and pathological increase in lumbar lordosis, which caused neuralgia radiating to the external genitalia and perineum, and overlapping with sexual pain. After diagnosing pudendal neuralgia according to the Nantes criteria, physical treatment and relaxation exercises to de-contract the spine were added to the vulvodynia regimen. During treatment, vulvodynia was sometimes present but never unbearable, allowing satisfactory sex. With physical therapy, the symptoms of pudendal neuralgia decreased. Differentiating the presence of two conditions with overlapping symptoms is difficult because the vestibular pain had shadowed pudendal neuralgia symptoms at initial assessment. Syndromes of chronic pain tend to associate with each other and one syndrome may shadow symptoms of the concomitant condition affecting adjacent anatomical areas. Only the accurate identification of all the syndromes involved allows adopting the correct treatment.

Neural electrical activity and neural network growth

The development of central and peripheral neural system depends in part on the emergence of the correct functional connectivity in its input and output pathways. Now it is generally accepted that molecular factors guide neurons to establish a primary scaffold that undergoes activity-dependent refinement for building a fully functional circuit. However, a number of experimental results obtained recently shows that the neuronal electrical activity plays an important role in the establishing of initial interneuronal connections. Nevertheless, these processes are rather difficult to study experimentally, due to the absence of theoretical description and quantitative parameters for estimation of the neuronal activity influence on growth in neural networks. In this work we propose a general framework for a theoretical description of the activity-dependent neural network growth. The theoretical description incorporates a closed-loop growth model in which the neural activity can affect neurite outgrowth, which in turn can affect neural activity. We carried out the detailed quantitative analysis of spatiotemporal activity patterns and studied the relationship between individual cells and the network as a whole to explore the relationship between developing connectivity and activity patterns. The model, developed in this work will allow us to develop new experimental techniques for studying and quantifying the influence of the neuronal activity on growth processes in neural networks and may lead to a novel techniques for constructing large-scale neural networks by self-organization.

Rho-associated kinase is a therapeutic target in neuroblastoma

Neuroblastoma is a peripheral neural system tumor that originates from the neural crest and is the most common and deadly tumor of infancy. Here we show that neuroblastoma harbors frequent mutations of genes controlling the Rac/Rho signaling cascade important for proper migration and differentiation of neural crest cells during neuritogenesis. RhoA is activated in tumors from neuroblastoma patients, and elevated expression of Rho-associated kinase (ROCK)2 is associated with poor patient survival. Pharmacological or genetic inhibition of ROCK1 and 2, key molecules in Rho signaling, resulted in neuroblastoma cell differentiation and inhibition of neuroblastoma cell growth, migration, and invasion. Molecularly, ROCK inhibition induced glycogen synthase kinase 3β-dependent phosphorylation and degradation of MYCN protein. Small-molecule inhibition of ROCK suppressed MYCN-driven neuroblastoma growth in TH-MYCN homozygous transgenic mice and MYCN gene-amplified neuroblastoma xenograft growth in nude mice. Interference with Rho/Rac signaling might offer therapeutic perspectives for high-risk neuroblastoma.

Abstract 5832: Rho-associated kinase is a therapeutic target in neuroblastoma

Abstract Background: Neuroblastoma is a peripheral neural system tumor that originates from the neural crest and is the most common and deadly tumor of infancy. The non-canonical Wnt/planar cell polarity (PCP) signaling pathway regulates cytoskeletal organization, migration and maturation of neural crest cells during neuritogenesis. Here we show that neuroblastoma harbors frequent mutations of genes controlling the PCP signaling pathway and Rac/Rho signaling cascade important for proper migration and differentiation of neural crest cells during neuritogenesis. The majority of these mutations were detected in GTPase activating proteins and guanine nucleotide exchange factors genes, which may result in inhibition of Rac and activation of Rho and was associated with aggressive high-stage neuroblastomas. Methods: We performed whole-exome sequencing of neuroblastoma samples of all clinical subgroups to search for mutations and genetic aberrations. Cytotoxic activity of Rho-associated kinases (ROCK) inhibitors was studied in cell viability assays. Morphology and invasion were studied with microscopy. The molecular mechanisms were characterized using cell- and molecular biology techniques. In vivo studies (xenografts and the transgenic mouse model TH-MYCN) in mice were carried out to validate the therapeutic effects and toxicity. Results: Exome sequencing detected frequent mutations and gene aberrations in genes controlling the activity of PCP signaling. Analysis of gene signatures and immunohistochemistry showed that high expression of ROCK1 and ROCK2 correlated with poor patient survival. Several mediators of Rac/Rho were differentially expressed in cell lines and patient samples. Pharmacological or genetic inhibition of ROCK, a key molecule in Rac/Rho signaling resulted in differentiation, inhibition of neuroblastoma cell growth and migration and degradation of MYCN protein. Finally, ROCK inhibition reduced the growth of established neuroblastoma xenografts in nude mice and repressed tumor progression in a MYCN-driven mouse model of neuroblastoma (T-MYCN) Conclusions: These results provide evidence that inhibition of the non-canonical/PCP signaling cascade using ROCK inhibitors suppress the growth of neuroblastoma in preclinical models and suggest possibilities for improved treatment of high-risk neuroblastomas. Citation Format: Cecilia H. Dyberg, Susanne Fransson, Teodora Andonova, Baldur Sveinbjörnsson, Jessika Lännerholm-Palm, David Forsberg, Eric Herlenius, Tommy Martinsson, Per Kogner, John Inge Johnsen, Malin Wickström. Rho-associated kinase is a therapeutic target in neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5832. doi:10.1158/1538-7445.AM2017-5832

The Role of Peripheral Myelin Protein 2 in Remyelination

The protein component of the myelin layer is essential for all aspects of peripheral nerves, and its deficiency can lead to structural and functional impairment. The presence of peripheral myelin protein 2 (P2, PMP2, FABP8, M-FABP) in Schwann cells has been known for decades and shown recently to be involved in the lipid homeostasis in the peripheral neural system. However, its precise role during de- and remyelination has yet to be elucidated. To this end, we assessed remyelination after sciatic nerve crush injury in vivo, and in an experimental de/remyelination ex vivo myelinating culture model in P2-deficient (P2 -/- ) and wild-type (WT) animals. In vivo, the nerve crush paradigm revealed temporal structural and functional changes in P2 -/- mice as compared to WT animals. Concomitantly, P2 -/- DRG cultures demonstrated the presence of shorter internodes and enlarged nodes after ex vivo de/remyelination. Together, these data indicate that P2 may play a role in remyelination of the injured peripheral nervous system, presumably by affecting the nodal and internodal configuration.

Use of human fat grafting in the prevention of perineural adherence: Experimental study in athymic mouse.

Perineural adherences represent a problem after surgery involving peripheral neural system. Fat-grafting with adipose derived stem cells (ASCs) with their pro-regenerative characteristics can be important to prevent the neural damage or to facilitate the neural regeneration. Our idea was to use the fat-grafting as an anti-adherence device and test its efficacy on a postsurgical scar animal model and comparing to an antiadhesive gel. 32 athymic mice were operated under magnification, we exposed both sciatic nerves. We randomly divided all sciatic nerves into four experimental groups: burning (1), burning + carboxy-methylcellulose and poly- ethylene oxide (CMC-PEO) (2) + human adipose fat tissue (3), control group (4). Bio-mechanical evaluation was performed to measure the peak force required to pull out the nerve from the muscular bed. Results: in the CMC-PEO group the peak pull out force was 0.37 Newton. In the fat grafted group we registered a peak pull out force of 0.35 N (t Student 0.913). In burning group the force necessary to tear the nerve apart was markedly superior (0.46 N). In control group, we reported the minimal strength (0.31 N) to slide the nerve from the tissue. Histologically, in the group treated with fat-grating, a thinner scar layer was highlighted. Considering the results of this study we can support the efficacy in animal experimental model of fat graft as an anti-adherence device in peripheral nerve surgery.

AN ANGLE-EMG BIOMECHANICAL MODEL OF THE HUMAN ELBOW JOINT

The biomechanical model of the human elbow joint is extensively studied. In the model, the surface electromyography (sEMG) is used as the input signal, whereas the muscle force or muscle torque is commonly considered as the output signal. The estimation of the actual muscle force or torque is important to effectively modulate the tremor suppression. However, the measurement of the muscle force or torque in vivo is difficult. In this paper, a new angle-to-EMG biomechanical model of the elbow joint was developed and evaluated by comparing the measured sEMG with the calculated sEMG. Three sources of the sEMG signal, namely, the central nervous system (CNS), the Golgi tendon and the muscle spindle were considered in this model. Furthermore, a local PID algorithm was proposed to describe the impact of the CNS on the motor neuron and the Golgi tendon model was used to transform muscle forces to stimulus signals. The model was calibrated by an improved search procedure combining the Powell search and the direct search to determine optimal model parameters. In the experiment, an sEMG signal acquisition system was established to measure the sEMG signal and the elbow joint angle. The experimental results, the predicted sEMG signal well following the measured sEMG, demonstrated that the calibrated model could be used to estimate in vivo sEMG signals and is beneficial to explore the peripheral neural system and the pathogenesis of tremor.

An integrated interface for peripheral neural system recording and stimulation: system design, electrical tests and in-vivo results.

The prototype of an electronic bi-directional interface between the Peripheral Nervous System (PNS) and a neuro-controlled hand prosthesis is presented. The system is composed of 2 integrated circuits: a standard CMOS device for neural recording and a HVCMOS device for neural stimulation. The integrated circuits have been realized in 2 different 0.35μ m CMOS processes available from ams. The complete system incorporates 8 channels each including the analog front-end, the A/D conversion, based on a sigma delta architecture and a programmable stimulation module implemented as a 5-bit current DAC; two voltage boosters supply the output stimulation stage with a programmable voltage scalable up to 17V. Successful in-vivo experiments with rats having a TIME electrode implanted in the sciatic nerve were carried out, showing the capability of recording neural signals in the tens of microvolts, with a global noise of 7μ V r m s , and to selectively elicit the tibial and plantar muscles using different active sites of the electrode.