RESUMEN
The peripheral nervous system consists of ganglia, nerve trunks, plexuses, and nerve endings, that transmit afferent and efferent information. Regeneration after a peripheral nerve damage is sluggish and imperfect. Peripheral nerve injury frequently causes partial or complete loss of motor and sensory function, physical impairment, and neuropathic pain, all of which have a negative impact on patients' quality of life. Because the mechanism of peripheral nerve injury and healing is still unclear, the therapeutic efficacy is limited. As peripheral nerve injury research has processed, an increasing number of studies have revealed that biological scaffolds work in tandem with progenitor cells to repair peripheral nerve injury. Here, we fabricated collagen chitosan nerve conduit bioscaffolds together with collagen and then filled neuroepithelial stem cells (NESCs). Scanning electron microscopy showed that the NESCs grew well on the scaffold surface. Compared to the control group, the NESCs group contained more cells with bigger diameters and myelinated structures around the axons. Our findings indicated that a combination of chitosan-collagen bioscaffold and neural stem cell transplantation can facilitate the functional restoration of peripheral nerve tissue, with promising future applications and research implications.
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Quitosano , Colágeno , Regeneración Nerviosa , Traumatismos de los Nervios Periféricos , Andamios del Tejido , Quitosano/química , Regeneración Nerviosa/fisiología , Colágeno/química , Animales , Andamios del Tejido/química , Traumatismos de los Nervios Periféricos/terapia , Ratas , Células Neuroepiteliales/citología , Células-Madre Neurales/citología , Nervios Periféricos/fisiología , Nervio Ciático/fisiologíaRESUMEN
Peripheral nerve injury (PNI) occurs due to damage of peripheral nerves, with healthcare professionals playing significant roles in PNI rehabilitation. This study aimed to explore the knowledge, attitudes, and practices (KAP) towards PNI rehabilitation among healthcare professionals. This cross-sectional study was conducted on June 2023 in China and healthcare professionals were enrolled. A total of 611 valid questionnaires were collected, with 62.52% female respondents. Mean scores for KAP were 14.26 ± 2.044 (possible range: 0-19), 29.77 ± 3.622 (possible range: 7-35), and 41.55 ± 9.523 (possible range: 11-55), respectively. Multivariate logistic regression revealed positive associations of professional titles (OR = 1.743, 95% CI: 1.083-2.804), occupation (OR = 1.833, 95% CI: 1.151-2.919), and involvement in treatment or care of PNI patients (OR = 1.462, 95% CI: 1.024-2.088) with knowledge. Knowledge (OR = 1.155, 95% CI: 1.042-1.280), gender (OR = 2.140, 95% CI: 1.255-3.646), education (OR = 2.258, 95% CI: 1.131-4.507), and involvement in treatment or care of PNI patients (OR = 2.463, 95% CI: 1.460-4.155) were positively associated with attitude. Attitude (OR = 1.214, 95% CI: 1.148-1.283), bachelor's degree education (OR = 0.548, 95% CI: 0.326-0.919), master's degree or higher (OR = 0.545, 95% CI: 0.308-0.964), having rehabilitation training for PNI (OR = 2.485, 95% CI: 1.633-3.781), and involvement in treatment or care of PNI patients (OR = 2.093, 95% CI: 1.395-3.138) were independently associated with practice. Healthcare professionals exhibited moderate knowledge, positive attitudes, and moderate practices towards the PNI rehabilitation. Those involved in the treatment or care of PNI have significantly higher KAP. Targeted interventions were needed to enhance understanding and promote proactive engagement in clinical practice.
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Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Traumatismos de los Nervios Periféricos , Humanos , Femenino , Masculino , Adulto , Personal de Salud/psicología , Estudios Transversales , Encuestas y Cuestionarios , Persona de Mediana Edad , Traumatismos de los Nervios Periféricos/rehabilitación , Traumatismos de los Nervios Periféricos/psicología , China , Actitud del Personal de Salud , Adulto JovenRESUMEN
Recent studies highlighted the role of platelet-rich plasma (PRP) in progenitor cell homing, migration, and nerve cell regeneration while also inhibiting fibrosis and apoptosis in cavernous nerve injury (CNI). The aim of this study was to investigate the effect of PRP administration on axon and collagen regeneration in CNI. A true experimental study using a post-test-only control group design was conducted. Twenty-five male Wistar rats (Rattus norvegicus), weighing 200-300 grams, were divided into five groups: two control groups (sham procedure and negative control), and three experimental groups receiving local PRP, intraperitoneal PRP, and a combination of local and intraperitoneal PRP. The cavernous nerve was injured with a hemostasis clamp for one minute before 200 µL of 200 PRP was injected locally, intraperitoneally, or both, depending on the group. After four weeks, the rats were euthanized, tissue segments (2 mm) from each cavernous nerve and mid-penis were collected and analyzed for collagen density, axon diameter, and number of myelinated axons. Our study found that collagen growth was slower in CNI group without PRP (sham procedure) compared to all PRP groups (local, intraperitoneal, and combination). The intraperitoneal PRP group had the highest collagen density at 5.62 µm; however, no significant difference was observed in collagen density among all groups (p=0.056). Similar axon diameter was found across the groups, with no statistically significant difference observed (p=0.856). In the number of myelinated axons, a significant difference was found among all groups with significantly more axons in local PRP and combined local and intraperitoneal PRP groups compared to others (p=0.026). In conclusion, PRP administration improved the number of myelinated axons in CNI, suggesting PRP role in CNI regeneration and the potential for an innovative approach to treating erectile dysfunction associated with CNI.
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Axones , Colágeno , Disfunción Eréctil , Regeneración Nerviosa , Pene , Plasma Rico en Plaquetas , Ratas Wistar , Animales , Masculino , Colágeno/metabolismo , Ratas , Regeneración Nerviosa/efectos de los fármacos , Regeneración Nerviosa/fisiología , Axones/fisiología , Axones/patología , Axones/efectos de los fármacos , Pene/inervación , Pene/efectos de los fármacos , Disfunción Eréctil/terapia , Disfunción Eréctil/tratamiento farmacológico , Modelos Animales de Enfermedad , Traumatismos de los Nervios Periféricos/terapiaRESUMEN
Application of polyethylene glycol (PEG) to a peripheral nerve injury at the time of primary neurorrhaphy is thought to prevent Wallerian degeneration via direct axolemma fusion. The molecular mechanisms of nerve fusion and recovery are unclear. Our study tested the hypothesis that PEG alters gene expression in neural and muscular environments as part of its restorative properties. Lewis rats underwent unilateral sciatic nerve transection with immediate primary repair. Subjects were randomly assigned to receive either PEG treatment or standard repair at the time of neurorrhaphy. Samples of sciatic nerve distal to the injury and tibialis muscle at the site of innervation were harvested at 24 hours and 4 weeks postoperatively. Total RNA sequencing and subsequent bioinformatics analyses were used to identify significant differences in differentially expressed genes (DEGs) and their related biological pathways (p<0.05) in PEG-treated subjects compared to non-PEG controls. No significant DEGs were identified in PEG-treated sciatic nerve compared to controls after 24 hours, but 1,480 DEGs were identified in PEG-treated tibialis compared to controls. At 4 weeks, 918 DEGs were identified in PEG-treated sciatic nerve, whereas only 3 DEGs remained in PEG-treated tibialis compared to controls. DEGs in sciatic were mostly upregulated (79%) and enriched in pathways present during nervous system development and growth, whereas DEGs in muscle were mostly downregulated (77%) and related to inflammation and tissue repair. Our findings indicate that PEG application during primary neurorrhaphy leads to significant differential gene regulation in the neural and muscular environment that is associated with improved functional recovery in animals treated with PEG compared to sham non-PEG controls. A detailed understanding of key molecules underlying PEG function in recovery after peripheral nerve repair may facilitate amplification of PEG effects through systemic or focal treatments at the time of neurotmesis.
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Músculo Esquelético , Traumatismos de los Nervios Periféricos , Polietilenglicoles , Ratas Endogámicas Lew , Nervio Ciático , Animales , Ratas , Nervio Ciático/lesiones , Traumatismos de los Nervios Periféricos/genética , Polietilenglicoles/farmacología , Músculo Esquelético/metabolismo , Músculo Esquelético/inervación , Músculo Esquelético/efectos de los fármacos , Modelos Animales de Enfermedad , Análisis de Secuencia de ARN , Regeneración Nerviosa/efectos de los fármacos , Regeneración Nerviosa/genética , Masculino , Regulación de la Expresión Génica/efectos de los fármacos , Perfilación de la Expresión GénicaRESUMEN
Peripheral nerve injuries (PNIs) are prevalent conditions mainly resulting from systemic causes, including autoimmune diseases and diabetes mellitus, or local causes, for example, chemical injury and perioperative nerve injury, which can cause a varying level of neurosensory disturbances (NSDs). Coenzyme Q10 (CoQ10) is an essential regulator of mitochondrial respiration and oxidative metabolism. Here, we review the pathophysiology of NSDs caused by PNIs, the current understanding of CoQ10's bioactivities, and its potential therapeutic roles in nerve regeneration, based on evidence from experimental and clinical studies involving CoQ10 supplementation. In summary, CoQ10 supplementation shows promise as a neuroprotective agent, potentially enhancing treatment efficacy for NSDs by reducing oxidative stress and inflammation. Future studies should focus on well-designed clinical trials with large sample sizes, using CoQ10 formulations with proven bioavailability and varying treatment duration, to further elucidate its neuroprotective effects and to optimize nerve regeneration in PNIs-induced NSDs.
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Fármacos Neuroprotectores , Estrés Oxidativo , Traumatismos de los Nervios Periféricos , Ubiquinona , Ubiquinona/análogos & derivados , Ubiquinona/uso terapéutico , Ubiquinona/farmacología , Humanos , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Traumatismos de los Nervios Periféricos/complicaciones , Animales , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Regeneración Nerviosa/efectos de los fármacos , Suplementos Dietéticos , InflamaciónRESUMEN
ABSTRACT: Peripheral nerve injuries (PNIs) represent a complex clinical challenge, necessitating precise diagnostic approaches for optimal management. Traditional diagnostic methods often fall short in accurately assessing nerve recovery as these methods rely on the completion of nerve reinnervation, which can prolong a patient's treatment. Diffusion tensor imaging (DTI), a noninvasive magnetic resonance imaging (MRI) technique, has emerged as a promising tool in this context. DTI offers unique advantages including the ability to quantify nerve recovery and provide in vivo visualizations of neuronal architecture. Therefore, this review aims to examine and outline DTI techniques and its utility in detecting distal nerve regeneration in both preclinical and clinical settings for peripheral nerve injury.
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Imagen de Difusión Tensora , Regeneración Nerviosa , Traumatismos de los Nervios Periféricos , Humanos , Traumatismos de los Nervios Periféricos/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Regeneración Nerviosa/fisiologíaRESUMEN
ABSTRACT: Magnetic resonance imaging (MRI) is a potentially powerful novel peripheral nerve diagnosis technique. To determine its validity, in-vivo preclinical studies are necessary. However, when using a rodent model, positioning rats and achieving high-resolution images can be challenging. We present a short report that outlines an optimal protocol for positioning rats for in-vivo MRI acquisition. Female Sprague-Dawley rats with sciatic nerve injury were induced into anesthesia using 4% isoflurane in oxygen and maintained at 1.5%. Rats were placed into a plexiglass cradle in a right lateral recumbent position, and a surface coil was placed over the left leg. Respiration rate and body temperature were monitored throughout the scan. Our protocol was successful as rats were able to undergo MRI scanning safely and efficiently. There were no adverse reactions, and clear images of the left sciatic nerve were obtained. Animal positioning took 30 minutes, and 5 different acquisitions were obtained in 2 hours. The total time from anesthesia induction to recovery was under 3 hours. Given the increasing interest in MRI diagnostic techniques, we hope this report aids other researchers studying peripheral nerve injury imaging in rat models.
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Imagen por Resonancia Magnética , Ratas Sprague-Dawley , Nervio Ciático , Animales , Imagen por Resonancia Magnética/métodos , Femenino , Ratas , Nervio Ciático/lesiones , Nervio Ciático/diagnóstico por imagen , Modelos Animales de Enfermedad , Traumatismos de los Nervios Periféricos/diagnóstico por imagenRESUMEN
An intratissual electrical stimulation, accompanied by irritation of their central neurons, is used to recover the function of damaged peripheral nerves. Treatment results exceeded those with the use of cutaneous electrical stimulation, which is confirmed by comparative results of trial animal experiments. The time and quality of peripheral nerves' function recovery in comparison of intratissual and cutaneous electrical stimulation methods remain unknown. OBJECTIVE: To evaluate the time and quality of peripheral nerves' functions recovery after their suturing and conducting two different methods of electrical stimulation, namely intratissual and cutaneous, in projection of central neurons of damaged spinal nerves in the postoperative period. MATERIAL AND METHODS: The basic technical parameters of the method of peripheral nerves' functions recovery in the postoperative period were ptacticed. Postoperative rehabilitation treatment was performed in 77 patients with traumatic peripheral nerves' injuries at the level of the forearm: in 42 with intratissual electrical stimulation, in 35 - using cutaneous one with similar characteristics of electrical current and concomitant pharmacological therapy. The follow-up duration was 2 years. RESULTS: A significant (in 4-6 times) reduction in time of treatment and a greater improvement in qualitative indicators when using intratissual electrical stimulation compared to the use of cutaneous stimulation were obtained. The effectiveness of the restorative therapy was dependent on the number of procedures, and a complete recovery of the damaged peripheral nerves' functions was observed after three courses of intratissual electrical stimulation. CONCLUSION: The time and degree of recovery of peripheral nerves' functions depends on the functional activity of their central neurons at the level of the spinal cord. The activation of these neurons by low-frequency electrical current allows to activate their trophic function. Thus, the cutaneous electrical stimulation does not cause the necessary level of irritation of the neurons due to the fact that the skin is a barrier to electrical current, which reduces its impact in 200-500 times. The intratissual electrical stimulation allows to solve the problem by supplying the needle-electrode much closer to the «target¼. The proposed method of intratissual electrical stimulation has shown its advantage over cutaneous electrical stimulation, significantly reducing the duration of the restorative treatment and increasing its qualitative indicators.
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Nervios Periféricos , Humanos , Masculino , Femenino , Nervios Periféricos/fisiología , Adulto , Traumatismos de los Nervios Periféricos/rehabilitación , Traumatismos de los Nervios Periféricos/terapia , Traumatismos de los Nervios Periféricos/fisiopatología , Terapia por Estimulación Eléctrica/métodos , Recuperación de la Función/fisiología , Persona de Mediana EdadRESUMEN
The rat sciatic nerve model is commonly used to test novel therapies for nerve injury repair. The static sciatic index (SSI) is a useful metric for quantifying functional recovery, and involves comparing an operated paw versus a control paw using a weighted ratio between the toe spread and the internal toe spread. To calculate it, rats are placed in a transparent box, photos are taken from underneath and the toe distances measured manually. This is labour intensive and subject to human error due to the challenge of consistently taking photos, identifying digits and making manual measurements. Although several commercial kits have been developed to address this challenge, they have seen little dissemination due to cost. Here we develop a novel algorithm for automatic measurement of SSI metrics based on video data using casted U-Nets. The algorithm consists of three U-Nets, one to segment the hind paws and two for the two pairs of digits which input into the SSI calculation. A training intersection over union error of 60 % and 80 % was achieved for the back paws and for both digit segmentation U-Nets, respectfully. The algorithm was tested against video data from three separate experiments. Compared to manual measurements, the algorithm provides the same profile of recovery for every experiment but with a tighter standard deviation in the SSI measure. Through the open-source release of this algorithm, we aim to provide an inexpensive tool to more reliably quantify functional recovery metrics to the nerve repair research community.
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Algoritmos , Modelos Animales de Enfermedad , Traumatismos de los Nervios Periféricos , Animales , Ratas , Traumatismos de los Nervios Periféricos/fisiopatología , Simulación por Computador , Nervio Ciático/fisiología , Nervio Ciático/lesiones , Ratas Sprague-DawleyRESUMEN
This study aimed to investigate the therapeutic potential of human adipose-derived mesenchymal stem cells (hADSCs) modified with recombinant adeno-associated virus (rAAV) carrying the vascular endothelial growth factor 165 (VEGF165) gene in peripheral nerve injury (PNI). The hADSCs were categorized into blank, control (transduced with rAAV control vector), and VEGF165 (transduced with rAAV VEGF165 vector) groups. Subsequently, Schwann cell differentiation was induced, and Schwann cell markers were assessed. The sciatic nerve injury mouse model received injections of phosphate-buffered saline (PBS group), PBS containing hADSCs (hADSCs group), rAAV control vector (control-hADSCs group), or rAAV VEGF165 vector (VEGF165-hADSCs group) into the nerve defect site. Motor function recovery, evaluated through the sciatic function index (SFI), and nerve regeneration, assessed via toluidine blue staining along with scrutiny of Schwann cell markers and neurotrophic factors, were conducted. Modified hADSCs exhibited enhanced Schwann cell differentiation and elevated expression of Schwann cell markers [S100 calcium-binding protein B (S100B), NGF receptor (NGFR), and glial fibrillary acidic protein (GFAP)]. Mice in the VEGF165-hADSCs group demonstrated improved motor function recovery compared to those in the other three groups, accompanied by increased fiber diameter, axon diameter, and myelin thickness, as well as elevated expression of Schwann cell markers (S100B, NGFR, and GFAP) and neurotrophic factors [mature brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF)] in the distal nerve segment. rAAV-VEGF165 modification enhances hADSC potential in PNI, promoting motor recovery and nerve regeneration. Elevated Schwann cell markers and neurotrophic factors underscore therapy benefits, providing insights for nerve injury strategies.
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Diferenciación Celular , Dependovirus , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Traumatismos de los Nervios Periféricos , Células de Schwann , Factor A de Crecimiento Endotelial Vascular , Humanos , Dependovirus/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Animales , Traumatismos de los Nervios Periféricos/terapia , Traumatismos de los Nervios Periféricos/metabolismo , Traumatismos de los Nervios Periféricos/genética , Células de Schwann/metabolismo , Ratones , Regeneración Nerviosa , Tejido Adiposo/citología , Tejido Adiposo/metabolismo , Vectores Genéticos , Nervio Ciático/lesiones , Nervio Ciático/patología , MasculinoRESUMEN
OBJECTIVE: To investigate the prevalence of upper limb peripheral nerve injuries (PNI) in adult patients admitted to the intensive care unit (ICU) with acute respiratory distress syndrome (ARDS) undergoing prone positioning. METHODS: This systematic review with meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines. Four electronic databases including PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), The Cochrane Library, and EMBASE were searched from inception to January 2024. The quality of the included studies was evaluated according to the Joanna Briggs Institute Critical Appraisal Tools. A proportion meta-analysis was conducted to examine the combined prevalence of upper limb PNI among patients requiring prone positioning. RESULTS: A total of 8 studies (511 patients) were pooled in the quantitative analysis. All studies had a low or moderate risk of bias in methodological quality. The overall proportion of patients with upper limb PNI was 13% (95%CI: 5% to 29%), with large between-study heterogeneity (I2 = 84.6%, P<0.001). Both ulnar neuropathy and brachial plexopathy were described in 4 studies. CONCLUSION: During the COVID-19 pandemic, prone positioning has been used extensively. Different approaches among ICU teams and selective reporting by untrained staff may be a factor in interpreting the large variability between studies and the 13% proportion of patients with upper limb PNI found in the present meta-analysis. Therefore, it is paramount to stress the importance of patient assessment both after discharge from the ICU and during subsequent follow-up evaluations. IMPLICATIONS FOR CLINICAL PRACTICE: Specialized training is essential to ensure safe prone positioning, with careful consideration given to arms and head placement to mitigate potential nerve injuries. Therefore, healthcare protocols should incorporate preventive strategies, with patient assessments conducted by expert multidisciplinary teams.
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Posicionamiento del Paciente , Traumatismos de los Nervios Periféricos , Síndrome de Dificultad Respiratoria , Extremidad Superior , Humanos , Posición Prona , Síndrome de Dificultad Respiratoria/etiología , Extremidad Superior/lesiones , Extremidad Superior/fisiopatología , Traumatismos de los Nervios Periféricos/etiología , Posicionamiento del Paciente/métodos , Unidades de Cuidados Intensivos/organización & administración , Unidades de Cuidados Intensivos/estadística & datos numéricos , COVID-19/complicacionesRESUMEN
Pig skeletal muscle-derived stem cells (SK-MSCs) were transplanted onto the common peroneal nerve with a collagen tube as a preclinical large animal experiment designed to address long nerve gaps. In terms of therapeutic usefulness, a human family case was simulated by adjusting the major histocompatibility complex to 50% and 100% correspondences. Swine leukocyte antigen (SLA) class I haplotypes were analyzed and clarified, as well as cell transplantation. Skeletal muscle-derived CD34+/45- (Sk-34) cells were injected into bridged tubes in two groups (50% and 100%) and with non-cell groups. Therapeutic effects were evaluated using sedentary/general behavior-based functional recovery score, muscle atrophy ratio, and immunohistochemistry. The results indicated that a two-Sk-34-cell-transplantation group showed clearly and significantly favorable functional recovery compared to a non-cell bridging-only group. Supporting functional recovery, the morphological reconstitution of the axons, endoneurium, and perineurium was predominantly evident in the transplanted groups. Thus, Sk-34 cell transplantation is effective for the regeneration of peripheral nerve gap injury. Additionally, 50% and 100% SLA correspondences were therapeutically similar and not problematic, and no adverse reaction was found in the 50% group. Therefore, the immunological response to Sk-MSCs is considered relatively low. The possibility of the Sk-MSC transplantation therapy may extend to the family members beyond the autologous transplantation.
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Antígenos de Histocompatibilidad Clase I , Músculo Esquelético , Traumatismos de los Nervios Periféricos , Animales , Porcinos , Traumatismos de los Nervios Periféricos/terapia , Antígenos de Histocompatibilidad Clase I/metabolismo , Regeneración Nerviosa , Recuperación de la Función , Trasplante Homólogo , Trasplante de Células Madre Mesenquimatosas/métodos , Trasplante de Células Madre/métodos , HumanosRESUMEN
Peripheral nerve injury (PNI) is a complex clinical challenge resulting in functional disability. Neurological recovery does not always ensure functional recovery, as extracellular matrix (ECM) alterations affect muscle function. This study evaluates hyaluronan (HA) and collagen concentration in the gastrocnemius muscle and thoracolumbar fascia (TLF) in unilateral lower limb PNI rats to explore systemic ECM alterations following PNI and their impacts on functional recovery. Eighteen 8-week-old male Sprague-Dawley rats were divided into experimental (n = 12 left sciatic nerve injury) and control (n = 6) groups. After six weeks, motor function was evaluated. Muscle and TLF samples were analysed for HA and collagen distribution and concentrations. SFI and gait analysis confirmed a functional deficit in PNI rats 6 weeks after surgery. HA concentration in both sides of the muscles decreased by approximately one-third; both sides showed significantly higher collagen concentration than healthy rats (12.74 ± 4.83 µg/g), with the left (32.92 ± 11.34 µg/g) significantly higher than the right (20.15 ± 7.03 µg/g). PNI rats also showed significantly lower HA (left: 66.95 ± 20.08 µg/g; right: 112.66 ± 30.53 µg/g) and higher collagen (left: 115.89 ± 28.18 µg/g; right: 90.43 ± 20.83 µg/g) concentrations in both TLF samples compared to healthy rats (HA: 167.18 ± 31.13 µg/g; collagen: 47.51 ± 7.82 µg/g), with the left TLF more affected. Unilateral lower limb PNI induced HA reduction and collagen accumulation in both the lower limb muscles and the TLF, potentially exacerbating motor function impairment and increasing the risk of low back dysfunctions.
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Colágeno , Matriz Extracelular , Fascia , Ácido Hialurónico , Extremidad Inferior , Músculo Esquelético , Ratas Sprague-Dawley , Nervio Ciático , Animales , Matriz Extracelular/metabolismo , Ratas , Masculino , Músculo Esquelético/metabolismo , Fascia/metabolismo , Fascia/patología , Colágeno/metabolismo , Nervio Ciático/lesiones , Nervio Ciático/metabolismo , Nervio Ciático/patología , Ácido Hialurónico/metabolismo , Traumatismos de los Nervios Periféricos/metabolismo , Traumatismos de los Nervios Periféricos/patologíaRESUMEN
INTRODUCTION: Isolated musculocutaneous nerve injuries occur rarely due to their anatomical location. We present our patient with a musculocutaneous nerve injury in a motorcyclist. CASE: The patient was initially treated for a motorcycle accident. Further examination of the patient revealed impaired elbow flexion and numbness of the lateral forearm. Electromyography confirmed impaired function of the musculocutaneous nerve. After 3 months, the patient's condition did not show any improvement, neither electromyography confirmed recovery of the nerve activity, so surgical treatment was planned. In the surgical revision, neuroma-in-continuity was discovered and resected. The resulting nerve defect was 6â cm long. We provided nerve grafting using sural nerve from the right lower limb. After surgery, the patient began physical therapy and electrical stimulation. Two years later, the patient reached complete recovery of muscle strength. CONCLUSION: Due to the lack of improvement after a 3-month period, we proceeded with a surgical revision, which demonstrated a complete lesion of the nerve that could not heal spontaneously. Therefore, we opted for the nerve graft method and the patient regained full function of elbow flexors.
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Accidentes de Tránsito , Motocicletas , Nervio Musculocutáneo , Humanos , Nervio Musculocutáneo/lesiones , Nervio Musculocutáneo/cirugía , Masculino , Adulto , Traumatismos de los Nervios Periféricos/cirugía , Nervio Sural/trasplanteRESUMEN
Neuritin, also known as candidate plasticity gene 15 (CPG15), was first identified as one of the activity-dependent gene products in the brain. Previous studies have been reported that Neuritin induces neuritogenesis, neurite arborization, neurite outgrowth and synapse formation, which are involved in the development and functions of the central nervous system. However, the role of Neuritin in peripheral nerve injury is still unknown. Given the importance and necessity of Schwann cell dedifferentiation response to peripheral nerve injury, we aim to investigate the molecular mechanism of Neuritin steering Schwann cell dedifferentiation during Wallerian degeneration (WD) in injured peripheral nerve. Herein, using the explants of sciatic nerve, an ex vivo model of nerve degeneration, we provided evidences indicating that Neuritin vividly accelerates Schwann cell dedifferentiation. Moreover, we found that Neuritin promotes Schwann cell demyelination as well as axonal degeneration, phagocytosis, secretion capacity. In summary, we first described Neuritin acts as a positive regulator for Schwann cell dedifferentiation and WD after peripheral nerve injury.
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Desdiferenciación Celular , Neuropéptidos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Células de Schwann , Nervio Ciático , Transducción de Señal , Serina-Treonina Quinasas TOR , Degeneración Walleriana , Células de Schwann/metabolismo , Células de Schwann/patología , Degeneración Walleriana/metabolismo , Degeneración Walleriana/patología , Animales , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Neuropéptidos/metabolismo , Neuropéptidos/genética , Nervio Ciático/lesiones , Nervio Ciático/metabolismo , Nervio Ciático/patología , Proteínas Ligadas a GPI/metabolismo , Proteínas Ligadas a GPI/genética , Ratas , Traumatismos de los Nervios Periféricos/metabolismo , Traumatismos de los Nervios Periféricos/patología , Ratas Sprague-Dawley , Axones/metabolismo , Axones/patología , Masculino , Fagocitosis , RatonesRESUMEN
The therapy of large defects in peripheral nerve injury (PNI) suffers from several drawbacks, especially the lack of autologous nerve donors. Nerve conduits are considered as a solution for nerve injury treatment, but biocompatibility improvements is still required for conduits prepared with synthetic materials. Cell-derived extracellular matrix (ECM) has drawn attention due to its lower risk of immunogenic response and independence from donor availability. The goal of this study is to coat bone mesenchymal stem cell-derived ECMs on poly(lactic-co-glycolic) acid (PLGA) conduits to enhance their ability to support neural growth and neurite extensions. The ECM-coated conduits have better hydrophilic properties than the pure PLGA conduits. A marked increase on PC12 and RSC96 cells' viability, proliferation and dorsal root ganglion neurite extension was observed. Quantitative PCR analysis exhibited a significant increase in markers for cell proliferation (GAP43), neurite extension (NF-H, MAP2, andßIII-tubulin) and neural function (TREK-1). These results show the potential of ECM-coated PLGA conduits in PNI therapy.
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Proliferación Celular , Supervivencia Celular , Matriz Extracelular , Células Madre Mesenquimatosas , Regeneración Nerviosa , Neuritas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Animales , Ratas , Neuritas/metabolismo , Células PC12 , Matriz Extracelular/metabolismo , Células Madre Mesenquimatosas/citología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Regeneración Nerviosa/efectos de los fármacos , Andamios del Tejido/química , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Ganglios Espinales , Traumatismos de los Nervios Periféricos/terapia , Ingeniería de Tejidos/métodos , Polímeros/química , Ensayo de MaterialesRESUMEN
BACKGROUND: Peripheral nerve injury is a challenging orthopedic issue in clinical management that often leads to limb dysfunction or even disability in severe cases. A thorough exploration of the repair process of peripheral nerve injury and the underlying mechanism contributes to formulate more effective therapeutic strategies. METHODS: In the present study, we established a sciatic nerve transection injury model in Sprague-Dawley (SD) rats. A 12-week compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis was then performed via sleeve jointing the proximal common peroneal nerve to the distal tibial nerve and common peroneal nerve, with a 2 mm interval. Compensatory repair via small gap amplification was observed via gross observation of nerve specimen, osmic acid staining, and electrophysiological stimulation of sciatic nerve branches of the tibial and common peroneal nerve. Rat limbs were observed, and the functional recovery of effector muscles of the gastrocnemius and tibialis anterior muscles was assessed through weighing the muscle wet weight, Hematoxylin and Eosin (H&E) staining, and muscle strength detection. H&E staining, Masson staining, and toluidine blue staining were performed to observe the morphological changes of the dorsal root ganglion. Positive expressions of key proteins involved in the Phosphatase and tensin homologue deleted on chromosome ten (PTEN)-protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, including PTEN, AKT, mTOR, Toll-like receptor 4 (TLR4), and Caspase9 in the dorsal root ganglion during compensatory repair of sciatic nerve after injury via small gap amplification, were detected by immunohistochemical staining. RESULTS: It is found that the compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis via sleeve jointing effectively restored the continuity, number of myelinated nerve fibers, and nerve conduction velocity. It promoted toe abduction recovery, improved muscle fiber morphology and increased the wet weight and muscle strength of the gastrocnemius muscle and tibialis anterior muscle. Moreover, it increased the number of neurons and nerve fibers, and improved their morphology. Downregulated PTEN, TLR4, and Caspase9 in the dorsal root ganglia and upregulated AKT and mTOR were observed after small gap amplification than those of the transection injury group, which were closer to those of the control group. CONCLUSIONS: Compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis via sleeve jointing can restore the morphology and function of the sciatic nerve, effector muscles, and corresponding dorsal root ganglia by activating the PTEN-AKT/mTOR signaling pathway in the dorsal root ganglia. Our findings provide novel therapeutic targets for peripheral nerve injuries.
Asunto(s)
Ganglios Espinales , Regeneración Nerviosa , Transducción de Señal , Animales , Masculino , Ratas , Modelos Animales de Enfermedad , Ganglios Espinales/metabolismo , Regeneración Nerviosa/fisiología , Traumatismos de los Nervios Periféricos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfohidrolasa PTEN/metabolismo , Ratas Sprague-Dawley , Nervio Ciático/lesiones , Neuropatía Ciática/metabolismo , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Peripheral nerve injury (PNI) often leads to retrograde cell death in the spinal cord and dorsal root ganglia (DRG), hindering nerve regeneration and functional recovery. Repetitive magnetic stimulation (rMS) promotes nerve regeneration following PNI. Therefore, this study aimed to investigate the effects of rMS on post-injury neuronal death and nerve regeneration. Seventy-two rats underwent autologous sciatic nerve grafting and were divided into two groups: the rMS group, which received rMS and the control (CON) group, which received no treatment. Motor neuron, DRG neuron, and caspase-3 positive DRG neuron counts, as well as DRG mRNA expression analyses, were conducted at 1-, 4-, and 8-weeks post-injury. Functional and axon regeneration analyses were performed at 8-weeks post-injury. The CON group demonstrated a decreased DRG neuron count starting from 1 week post-injury, whereas the rMS group exhibited significantly higher DRG neuron counts at 1- and 4-weeks post-injury. At 8-weeks post-injury, the rMS group demonstrated a significantly greater myelinated nerve fiber density in autografted nerves. Furthermore, functional analysis showed significant improvements in latency and toe angle in the rMS group. Overall, these results suggest that rMS can prevent DRG neuron death and enhance nerve regeneration and motor function recovery after PNI.
Asunto(s)
Muerte Celular , Modelos Animales de Enfermedad , Ganglios Espinales , Regeneración Nerviosa , Traumatismos de los Nervios Periféricos , Nervio Ciático , Animales , Ganglios Espinales/metabolismo , Ratas , Nervio Ciático/lesiones , Traumatismos de los Nervios Periféricos/terapia , Masculino , Ratas Sprague-Dawley , Neuronas/metabolismo , Magnetoterapia/métodos , Recuperación de la Función , Neuronas Motoras/metabolismo , Neuronas Motoras/fisiologíaRESUMEN
Peripheral nerve injury is a major societal concern. Black phosphorus (BP) has inherent advantages over cell-based therapies in regenerative medicine. However, controlling spontaneous degradation and size-dependent cytotoxicity remains challenging and poses difficulties for clinical translation. In this study, we constructed zero-dimensional BP quantum dots (QDs) modified with antioxidant ß-carotene and comprehensively investigated them in Schwann cells (SCs) to elucidate their potential for peripheral nerve repair. In vitro experiments demonstrated that BPQD@ß-carotene has an inappreciable toxicity and good biocompatibility, favoring neural regrowth, angiogenesis, and inflammatory regulation of SCs. Furthermore, the PI3K/Akt and Ras/ERK1/2 signaling pathways were activated in SCs at the genetic, protein, and metabolite levels. The BPQD@ß-carotene-embedded GelMA/PEGDA scaffold enhanced functional recovery by promoting axon remyelination and regeneration and facilitating intraneural angiogenesis in peripheral nerve injury models of rats and beagle dogs. These results contribute to advancing knowledge of BP nanomaterials in tissue regeneration and show significant potential for application in translational medicine.
Asunto(s)
Antioxidantes , Regeneración Nerviosa , Traumatismos de los Nervios Periféricos , Fósforo , Puntos Cuánticos , Ratas Sprague-Dawley , Células de Schwann , Animales , Regeneración Nerviosa/efectos de los fármacos , Puntos Cuánticos/química , Traumatismos de los Nervios Periféricos/metabolismo , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Traumatismos de los Nervios Periféricos/patología , Antioxidantes/farmacología , Antioxidantes/química , Ratas , Perros , Fósforo/química , Células de Schwann/efectos de los fármacos , Células de Schwann/metabolismo , Masculino , Células CultivadasRESUMEN
Neuropathic pain is characterised by periodic or continuous hyperalgesia, numbness, or allodynia, and results from insults to the somatosensory nervous system. Peripheral nerve injury induces transcriptional reprogramming in peripheral sensory neurons, contributing to increased spinal nociceptive input and the development of neuropathic pain. Effective treatment for neuropathic pain remains an unmet medical need as current therapeutics offer limited effectiveness and have undesirable effects. Understanding transcriptional changes in peripheral nerve injury-induced neuropathy might offer a path for novel analgesics. Our literature search identified 65 papers exploring transcriptomic changes post-peripheral nerve injury, many of which were conducted in animal models. We scrutinize their transcriptional changes data and conduct gene ontology enrichment analysis to reveal their common functional profile. Focusing on genes involved in 'sensory perception of pain' (GO:0019233), we identified transcriptional changes for different ion channels, receptors, and neurotransmitters, shedding light on its role in nociception. Examining peripheral sensory neurons subtype-specific transcriptional reprograming and regeneration-associated genes, we delved into downstream regulation of hypersensitivity. Identifying the temporal program of transcription regulatory mechanisms might help develop better therapeutics to target them effectively and selectively, thus preventing the development of neuropathic pain without affecting other physiological functions.