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1.
Neurosci Lett ; 824: 137691, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38373630

RESUMO

Enhancing axonal regeneration is one of the most important processes in treating nerve injuries. Both magnetic and electrical stimulation have the effect of promoting nerve axon regeneration. But few study has investigated the effects of trans-spinal magnetic stimulation (TsMS) combined with electroacupuncture (EA) on nerve regeneration in rats with sciatic nerve injury. In this study, we compared the improvement of neurological function in rats with sciatic nerve crush injuries after 4 weeks of different interventions (EA, TsMS, or TsMS combined with EA). We further explored the morphological and molecular biological alterations following sciatic nerve injury by HE, Masson, RT-PCR, western blotting, immunofluorescence staining and small RNA transcriptome sequencing. The results showed that TsMS combined with EA treatment significantly promoted axonal regeneration, increased the survival rate of neurons, and suppressed denervation atrophy of the gastrocnemius muscle. Subsequent experiments suggested that the combination treatment may play an active role by mediating the miR-539-5p/Sema3A/PlexinA1 signaling axis.


Assuntos
Eletroacupuntura , MicroRNAs , Traumatismos dos Nervos Periféricos , Neuropatia Ciática , Ratos , Animais , Ratos Sprague-Dawley , Semaforina-3A/farmacologia , Axônios , Regeneração Nervosa/fisiologia , Nervo Isquiático/lesões , Neuropatia Ciática/terapia , Traumatismos dos Nervos Periféricos/terapia , MicroRNAs/genética , MicroRNAs/farmacologia
2.
Neurol Res ; 46(4): 356-366, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38402903

RESUMO

OBJECTIVES: We ascertained that the PET scan may be a valuable imaging modality for the noninvasive, objective diagnosis of neuropathic pain caused by peripheral nerve injury through the previous study. This study aimed to assess peripheral nerve damage according to severity using18F-FDG PET/MRI of the rat sciatic nerve. METHODS: Eighteen rats were divided into three groups: 30-second (G1), 2-minute (G2), and 5-minute (G3) crushing injuries. The severity of nerve damage was measured in the third week after the crushing injury using three methods: the paw withdrawal threshold test (RevWT), standardized uptake values on PET (SUVR), and intensity analysis on immunohistochemistry (IntR). RESULTS: There were significant differences between G1 and G3 in both SUVR and IntR (p = 0.012 and 0.029, respectively), and no significant differences in RevWT among the three groups (p = 0.438). There was a significant difference in SUVR (p = 0.012), but no significant difference in IntR between G1 and G2 (p = 0.202). There was no significant difference between G2 and G3 in SUVR and IntR (p = 0.810 and 0.544, respectively). DISCUSSION: Although PET did not show results consistent with those of immunohistochemistry in all respects, this study demonstrated that PET uptake tended to increase with severe nerve damage. If this research is supplemented by further experiments, PET/MRI can be used as an effective diagnostic modality.


Assuntos
Traumatismos dos Nervos Periféricos , Neuropatia Ciática , Ratos , Animais , Fluordesoxiglucose F18 , Compostos Radiofarmacêuticos , Traumatismos dos Nervos Periféricos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Imageamento por Ressonância Magnética/métodos , Neuropatia Ciática/diagnóstico por imagem , Nervo Isquiático/diagnóstico por imagem
3.
Pharmacol Res ; 200: 107076, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38237646

RESUMO

Sciatica characterized by irritation, inflammation, and compression of the lower back nerve, is considered one of the most common back ailments globally. Currently, the therapeutic regimens for sciatica are experiencing a paradigm shift from the conventional pharmacological approach toward exploring potent phytochemicals from medicinal plants. There is a dire need to identify novel phytochemicals with anti-neuropathic potential. This review aimed to identify the potent phytochemicals from diverse medicinal plants capable of alleviating neuropathic pain associated with sciatica. This review describes the pathophysiology of sciatic nerve pain, its cellular mechanisms, and the pharmacological potential of various plants and phytochemicals using animal-based models of sciatic nerve injury-induced pain. Extensive searches across databases such as Medline, PubMed, Web of Science, Scopus, ScienceDirect, and Google Scholar were conducted. The findings highlights 39 families including Lamiaceae, Asteraceae, Fabaceae, and Apocyanaceae and Cucurbitaceae, effectively treating sciatic nerve injury-induced pain. Flavonoids made up 53% constituents, phenols and terpenoids made up 15%, alkaloids made up 13%, and glycosides made up 6% to be used in neuorpathic pain. Phytochemicals derived from various medicinal plants can serve as potential therapeutic targets for both acute and chronic sciatic injury-induced neuropathic pain.


Assuntos
Neuralgia , Plantas Medicinais , Neuropatia Ciática , Ciática , Animais , Humanos , Plantas Medicinais/química , Ciática/tratamento farmacológico , Ciática/etiologia , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Neuropatia Ciática/tratamento farmacológico , Inflamação/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/química , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química
4.
Histochem Cell Biol ; 161(2): 145-163, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37855874

RESUMO

Peripheral nerve injuries lead to significant changes in the dorsal root ganglia, where the cell bodies of the damaged axons are located. The sensory neurons and the surrounding satellite cells rearrange the composition of the intracellular organelles to enhance their plasticity for adaptation to changing conditions and response to injury. Meanwhile, satellite cells acquire phagocytic properties and work with macrophages to eliminate degenerated neurons. These structural and functional changes are not identical in all injury types. Understanding the cellular response, which varies according to the type of injury involved, is essential in determining the optimal method of treatment. In this research, we investigated the numerical and morphological changes in primary sensory neurons and satellite cells in the dorsal root ganglion 30 days following chronic compression, crush, and transection injuries using stereology, high-resolution light microscopy, immunohistochemistry, and behavioral analysis techniques. Electron microscopic methods were employed to evaluate fine structural alterations in cells. Stereological evaluations revealed no statistically significant difference in terms of mean sensory neuron numbers (p > 0.05), although a significant decrease was observed in sensory neuron volumes in the transection and crush injury groups (p < 0.05). Active caspase-3 immunopositivity increased in the injury groups compared to the sham group (p < 0.05). While crush injury led to desensitization, chronic compression injury caused thermal hyperalgesia. Macrophage infiltrations were observed in all injury types. Electron microscopic results revealed that the chromatolysis response was triggered in the sensory neuron bodies from the transection injury group. An increase in organelle density was observed in the perikaryon of sensory neurons after crush-type injury. This indicates the presence of a more active regeneration process in crush-type injury than in other types. The effect of chronic compression injury is more devastating than that of crush-type injury, and the edema caused by compression significantly inhibits the regeneration process.


Assuntos
Lesões por Esmagamento , Traumatismos dos Nervos Periféricos , Neuropatia Ciática , Ratos , Animais , Gânglios Espinais/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Neuropatia Ciática/metabolismo , Nervo Isquiático/lesões , Lesões por Esmagamento/metabolismo
5.
Mol Neurobiol ; 61(2): 935-949, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37672149

RESUMO

Although the benefits of electroacupuncture (EA) for peripheral nerve injury (PNI) are well accepted in clinical practice, the underlying mechanism remains incompletely elucidated. In our study, we observed that EA intervention led to a reduction in the expression of the long non-coding RNA growth-arrest-specific transcript 5 (GAS5) and an increased in miR-21 levels within the injured nerve, effectively promoting functional recovery and nerve regeneration following sciatic nerve injury (SNI). In contrast, administration of adeno-associated virus expressing GAS5 (AAV-GAS5) weakened the therapeutic effect of EA. On the other hand, both silencing GAS5 and introducing a miR-21 mimic prominently enhanced the proliferation activity and migration ability of Schwann cells (SCs), while also inhibiting SCs apoptosis. On the contrary, inhibition of SCs apoptosis was found to be mediated by miR-21. Additionally, overexpression of GAS5 counteracted the effects of the miR-21 mimic on SCs. Moreover, SCs that transfected with the miR-21 mimic promoted neurite growth in hypoxia/reoxygenation-induced neurons, which might be prevented by overexpressing GAS5. Furthermore, GAS5 was found to be widely distributed in the cytoplasm and was negatively regulated by miR-21. Consequently, the targeting of GAS5 by miR-21 represents a potential mechanism through which EA enhances reinnervation and functional restoration following SNI. Mechanistically, the GAS5/miR-21 axis can modulate the proliferation, migration, and apoptosis of SCs while potentially influencing the neurite growth of neurons.


Assuntos
Eletroacupuntura , MicroRNAs , Traumatismos dos Nervos Periféricos , RNA Longo não Codificante , Neuropatia Ciática , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Traumatismos dos Nervos Periféricos/terapia , Traumatismos dos Nervos Periféricos/metabolismo , Neuropatia Ciática/metabolismo , Regeneração Nervosa/fisiologia , Nervo Isquiático/metabolismo
6.
Neurochem Res ; 49(4): 949-958, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38157112

RESUMO

The study was aimed to validate the efficacy of the pulsed Nd:YAG laser on nerve regeneration in a rat sciatic nerve crushed model. 54 Wistar rats were randomly assigned into three groups: shame control, crush control, and laser treated group. For the laser treated group, the pulsed Nd:YAG laser (10 Hz) with 350 mJ per pulse in energy density and 50 J/cm2 in fluence was applied extracorporeally at the lesion site for 12 min to daily deliver 500 J immediately and consecutive 9 days following the crush injury. At week 1, the apoptosis-related activities in the injured nerve were examined (n = 8/each group). The sciatic functional index (SFI) was measured preoperatively and weekly until 4 weeks after the index procedure. The injured nerve and the innervated gastrocnemius muscle histology were assessed at week 4 (n = 10/each group). At week 1, the laser group showed the significant less TUNEL-positive ratio (P < 0.05), and the lower expression of cleaved caspase3/procaspase-3 and beclin-2/beclin-2-associated protein X ratios compared with the crush control. Furthermore, the laser group revealed significantly better SFI since week 1 and throughout the study (P < 0.05, all) compared with the crush control. At week 4, the laser group showed significantly higher axon density, lower myelin g-ratio, and the corresponding higher glycogen expression (P < 0.05, all) in the gastrocnemius muscle compared with those in the crush control. The pulsed Nd:YAG might enhance the injured nerve regeneration via apoptosis inhibition.


Assuntos
Lesões por Esmagamento , Terapia a Laser , Lasers de Estado Sólido , Neuropatia Ciática , Ratos , Animais , Ratos Wistar , Compressão Nervosa , Nervo Isquiático/lesões , Regeneração Nervosa/fisiologia , Neuropatia Ciática/patologia
7.
Brain Behav Immun ; 115: 419-431, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37924957

RESUMO

Regular aerobic activity is associated with a reduced risk of chronic pain in humans and rodents. Our previous studies in rodents have shown that prior voluntary wheel running can normalize redox signaling at the site of peripheral nerve injury, attenuating subsequent neuropathic pain. However, the full extent of neuroprotection offered by voluntary wheel running after peripheral nerve injury is unknown. Here, we show that six weeks of voluntary wheel running prior to chronic constriction injury (CCI) reduced the terminal complement membrane attack complex (MAC) at the sciatic nerve injury site. This was associated with increased expression of the MAC inhibitor CD59. The levels of upstream complement components (C3) and their inhibitors (CD55, CR1 and CFH) were altered by CCI, but not increased by voluntary wheel running. Since MAC can degrade myelin, which in turn contributes to neuropathic pain, we evaluated myelin integrity at the sciatic nerve injury site. We found that the loss of myelinated fibers and decreased myelin protein which occurs in sedentary rats following CCI was not observed in rats with prior running. Substitution of prior voluntary wheel running with exogenous CD59 also attenuated mechanical allodynia and reduced MAC deposition at the nerve injury site, pointing to CD59 as a critical effector of the neuroprotective and antinociceptive actions of prior voluntary wheel running. This study links attenuation of neuropathic pain by prior voluntary wheel running with inhibition of MAC and preservation of myelin integrity at the sciatic nerve injury site.


Assuntos
Neuralgia , Traumatismos dos Nervos Periféricos , Neuropatia Ciática , Humanos , Ratos , Animais , Bainha de Mielina/metabolismo , Complexo de Ataque à Membrana do Sistema Complemento , Atividade Motora/fisiologia , Traumatismos dos Nervos Periféricos/complicações , Hiperalgesia/metabolismo , Neuralgia/complicações , Nervo Isquiático/lesões
8.
Biomed Mater ; 19(1)2023 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-38091624

RESUMO

Despite recent technological advancements, effective healing from sciatic nerve damage remains inadequate. Cell-based therapies offer a promising alternative to autograft restoration for peripheral nerve injuries, and 3D printing techniques can be used to manufacture conduits with controlled diameter and size. In this study, we investigated the potential of Wharton's jelly-derived mesenchymal stem cells (WJMSCs) differentiated into schwann cells, using a polyacrylonitrile (PAN) conduit filled with fibrin hydrogel and graphene quantum dots (GQDs) to promote nerve regeneration in a rat sciatic nerve injury model. We investigated the potential of WJMSCs, extracted from the umbilical cord, to differentiate into schwann cells and promote nerve regeneration in a rat sciatic nerve injury model. WJMSCs were 3D cultured and differentiated into schwann cells within fibrin gel for two weeks. A 3 mm defect was created in the sciatic nerve of the rat model, which was then regenerated using a conduit/fibrin, conduit covered with schwann cells in fibrin/GQDs, GQDs in fibrin, and a control group without any treatment (n= 6/group). At 10 weeks after transplantation, motor and sensory functions and histological improvement were assessed. The WJMSCs were extracted, identified, and differentiated. The differentiated cells expressed typical schwann cell markers, S100 and P75.In vivoinvestigations established the durability and efficacy of the conduit to resist the pressures over two months of implantation. Histological measurements showed conduit efficiency, schwann cell infiltration, and association within the fibrin gel and lumen. Rats treated with the composite hydrogel-filled PAN conduit with GQDs showed significantly higher sensorial recovery than the other groups. Histological results showed that this group had significantly more axon numbers and remyelination than others. Our findings suggest that the conduit/schwann approach has the potential to improve nerve regeneration in peripheral nerve injuries, with future therapeutic implications.


Assuntos
Grafite , Traumatismos dos Nervos Periféricos , Pontos Quânticos , Neuropatia Ciática , Ratos , Animais , Traumatismos dos Nervos Periféricos/terapia , Traumatismos dos Nervos Periféricos/patologia , Hidrogéis , Células de Schwann/fisiologia , Regeneração Nervosa/fisiologia , Nervo Isquiático/lesões , Neuropatia Ciática/patologia , Fibrina , Impressão Tridimensional
9.
Toxins (Basel) ; 15(12)2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38133195

RESUMO

This study was designed to compare the effects of various doses of botulinum neurotoxin A (BoNT/A) on nerve regeneration. Sixty-five six-week-old rats with sciatic nerve injury were randomly allocated to three experimental groups, a control group, and a sham group. The experimental groups received a single session of intraneural BoNT/A (3.5, 7.0, or 14 U/kg) injection immediately after nerve-crushing injury. The control group received normal intraneural saline injections after sciatic nerve injury. At three, six, and nine weeks after nerve damage, immunofluorescence staining, an ELISA, and toluidine blue staining was used to evaluate the regenerated nerves. Serial sciatic functional index analyses and electrophysiological tests were performed every week for nine weeks. A higher expression of GFAP, S100ß, GAP43, NF200, BDNF, and NGF was seen in the 3.5 U/kg and 7.0 U/kg BoNT/A groups. The average area and myelin thickness were significantly greater in the 3.5 U/kg and 7.0 U/kg BoNT/A groups. The sciatic functional index and compound muscle action potential amplitudes exhibited similar trends. These findings indicate that the 3.5 U/kg and 7.0 U/kg BoNT/A groups exhibited better nerve regeneration than the 14 U/kg BoNT/A and control group. As the 3.5 U/kg and the 7.0 U/kg BoNT/A groups exhibited no statistical difference, we recommend using 3.5 U/kg BoNT/A for its cost-effectiveness.


Assuntos
Toxinas Botulínicas Tipo A , Traumatismos dos Nervos Periféricos , Neuropatia Ciática , Ratos , Animais , Toxinas Botulínicas Tipo A/farmacologia , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Traumatismos dos Nervos Periféricos/metabolismo , Regeneração Nervosa , Nervo Isquiático/lesões
10.
Cell Physiol Biochem ; 57(6): 452-477, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37978922

RESUMO

BACKGROUND/AIMS: All body functions are activated, synchronized and controlled by a substantial, complex network, the nervous system. Upon injury, pathophysiology of the nerve injury proceeds through different paths. The axon may undergo a degenerative retraction from the site of injury for a short distance unless the injury is near to the cell body, in which case it continues to the soma and undergoes retrograde neuronal degeneration. Otherwise, the distal section suffers from Wallerian degeneration, which is marked by axonal swelling, spheroids, and cytoskeleton degeneration. The objective of the study was to evaluate the potential of mesenchymal stem cell laden neural scaffold and insulin-like growth factor I (IGF-I) in nerve regeneration following sciatic nerve injury in a rat model. METHODS: The animals were anaesthetized and a cranio-lateral incision over left thigh was made. Sciatic nerve was exposed and crush injury was introduced for 90 seconds using haemostat at second locking position. The muscle and skin were sutured in routine fashion and thus the rat model of sciatic crush injury was prepared. The animal models were equally distributed into 5 different groups namely A, B, C, D and E and treated with phosphate buffer saline (PBS), carbon nanotubes based neural scaffold only, scaffold with IGF-I, stem cell laden scaffold and stem cell laden scaffold with IGF-I respectively. In vitro scaffold testing was performed. The nerve regeneration was assessed based on physico-neuronal, biochemical, histopathological examination, and relative expression of NRP-1, NRP-2 and GAP-43 and scanning electron microscopy. RESULTS: Sciatic nerve injury model with crush injury produced for 90 seconds was standardized and successfully used in this study. All the biochemical parameters were in normal range in all the groups indicating no scaffold related changes. Physico-neuronal, histopathological, relative gene expression and scanning electron microscopy observations revealed appreciable nerve regeneration in groups E and D, followed by C and B. Restricted to no regeneration was observed in group A. CONCLUSION: Carbon nanotubes based scaffold provided electro-conductivity for proper neuronal regeneration while rat bone marrow-derived mesenchymal stem cells were found to induce axonal sprouting, cellular transformation; whereas IGF-I induced stem cell differentiation, myelin synthesis, angiogenesis and muscle differentiation.


Assuntos
Lesões por Esmagamento , Células-Tronco Mesenquimais , Nanotubos de Carbono , Neuropatia Ciática , Ratos , Animais , Ratos Wistar , Fator de Crescimento Insulin-Like I/farmacologia , Fator de Crescimento Insulin-Like I/uso terapêutico , Neuropatia Ciática/tratamento farmacológico , Neuropatia Ciática/patologia , Nervo Isquiático/lesões , Regeneração Nervosa/fisiologia , Lesões por Esmagamento/tratamento farmacológico , Lesões por Esmagamento/patologia , Células-Tronco Mesenquimais/patologia , Colágeno
11.
BMJ Case Rep ; 16(11)2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37923338

RESUMO

SummarySciatic nerve injury after total hip replacement is rare with a reported incidence of about 0.09%-3.7%. The most commonly reported causes include traction on the nerve during reduction, compression of the nerve from subfascial haematoma, significant leg lengthening, improper retractor placement, thermal burns from cautery and extraneous cement. We present a case of complete sciatic nerve palsy in a patient operated on using direct anterior approach (DAA). To date, there are no reports describing sciatic nerve palsy secondary to haematoma immediately after primary arthroplasty through the DAA. We performed an MRI of lumbosacral spine with both hips, which revealed a haematoma. Consequently, we promptly took the patient to the operation theatre for re-exploration. Using the same approach, we dislocated the hip and removed the clots. By the end of 2 weeks, the patient was able to dorsiflex the ankle and had fully recovered from sciatic nerve palsy.


Assuntos
Artroplastia de Quadril , Neuropatia Ciática , Humanos , Artroplastia de Quadril/efeitos adversos , Hematoma/complicações , Quadril , Nervo Isquiático , Neuropatia Ciática/etiologia , Pessoa de Meia-Idade
12.
Neurosci Lett ; 817: 137514, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37848102

RESUMO

Cyclin-dependent kinase 5 regulatory subunit 1 (CDK5R1) is necessary for central nervous system development and neuronal migration. At present, there are few reports about the role of CDK5R1 in peripheral nerve injury, and these need to be further explored. The CCK-8 and EdU assay was performed to examine cell proliferation. The migration ability of Schwann cells was tested by the cell scratch test. The apoptosis of Schwann cells was detected by flow cytometry. Sciatic nerve injury model in rats was established by crush injury. The sciatic function index (SFI) and the paw withdrawal mechanical threshold (PWMT) were measured at different time points. The results revealed that overexpression of CDK5R1 promoted the proliferation and migration of Schwann cells, and inhibited the apoptosis. Further studies found that pcDNA3.1-CDK5R1 significantly upregulated the expression of CDK5, BDNF and TrkB. More importantly, CDK5R1 promoted the recovery of nerve injury in rats. In addition, the CDK5 mediated BDNF/TrkB pathway was involved in the molecular mechanism of CDK5R1 on Schwann cells. It is suggested that the mechanism by which CDK5R1 promotes functional recovery after sciatic nerve injury is by CDK5 mediated activation of BDNF/TrkB signaling pathways.


Assuntos
Traumatismos dos Nervos Periféricos , Fosfotransferases , Neuropatia Ciática , Animais , Ratos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proliferação de Células , Quinase 5 Dependente de Ciclina/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Células de Schwann/metabolismo , Nervo Isquiático/lesões , Neuropatia Ciática/metabolismo , Fosfotransferases/metabolismo
13.
Neurol Res ; 45(11): 1035-1043, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37702221

RESUMO

BACKGROUND: Peripheral nerve injury is a common disorder associated with damaged axons and distal myelin sheath degeneration, and Schwann cells play a paramount role in peripheral nerve regeneration. This study aims to explore the role of microRNA miR-148b-3p on Schwann cells after peripheral nerve injury. METHODS: Sciatic nerve transection was conducted in rat as the model of peripheral nerve injury. The expression level of miR-148b-3p and Ubiquitin Specific Peptidase 6 (USP6) was detected by qRT-PCR and Western blot at diverse time points after nerve transection. Cell migration and proliferation were determined in primary Schwann cells isolated from rat. The functional interaction of miR-148b-3p and USP6 mRNA was validated by dual-luciferase reporter assay. RESULTS: In the animal model of sciatic nerve injury, miR-148b-3p expression level in the proximal nerve stump showed downregulation after nerve transection procedure, while USP6 expression level was elevated. The overexpression of miR-148b-3p inhibited the proliferation and migration of primary Schwann cells, while suppressing miR-148b-3p showed the opposite effect. USP6 mRNA was identified as a target of miR-148b-3p, which was found to mediate the effect of miR-148b-3p. USP6 silencing suppressed the migration and proliferation in primary Schwann cells. CONCLUSION: Our data demonstrated the functional role of miR-148b-3p/USP6 axis in regulating the migration and proliferation of Schwann cells following peripheral nerve injury. miR-148b-3p showed downregulation and its target USP6 was upregulated after nerve transection procedure. Targeting miR-148b-3p/USP6 axis may provide a novel opportunity for peripheral nerve repair.


Assuntos
MicroRNAs , Traumatismos dos Nervos Periféricos , Neuropatia Ciática , Ratos , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Células de Schwann , Nervo Isquiático/lesões , Proliferação de Células/genética , RNA Mensageiro/metabolismo
14.
Neurosci Lett ; 813: 137429, 2023 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-37574162

RESUMO

Neuropathic pain refers to a type of pain that arises from primary damage and dysfunction within the nervous system. Addressing this condition presents significant challenges and complexities. Betulinic acid (BA), known for its potent antioxidative and anti-inflammatory properties, has garnered extensive attention; nevertheless, the impact upon neuropathic pain induced by CCI is still uncertain. This paper explores the analgesic effects concerning BA on mice experiencing neuropathic pain due to sciatic nerve injury. Throughout the experiment, mice with CCI received oral gavage of BA at dosages of 3, 10, and 30 mg/kg for consecutively 8 days from the 7th day post-surgery. To assess their responses, behavioral tests and sciatic functional index (SFI) evaluations were conducted on zeroth, seventh, eighth, tenth, twelveth and fourteenth day post-CCI. On day 14, histopathological examinations and measurements of biochemical markers were performed. Immunofluorescence techniques were employed to detect Nrf2 and glial cell activation, while the Western blot method was utilized to evaluate Nrf2/HO-1 protein levels and pro-inflammatory cytokine expression. The results elucidated that BA significantly alleviated hyperalgesia and allodynia, demonstrating a dose-dependent enhancement in sciatic nerve function and facilitating the recovery of sciatic nerve injury. Furthermore, BA prominently augmented the entire antioxidative capacity (T-AOC) and T-SOD levels, concomitantly reducing MDA concentrations. Notably, BA activated the Nrf2/HO-1 signaling pathway, inhibited glial cell activation, and downregulation of the expression levels of pro-inflammatory cytokines, specifically, TNF-α, IL-1ß, and IL-6 were observed. As such, this study provides a basis to support BA as a candidate drug for the treatment of neuropathic pain, attributing its analgesic effects to its anti-inflammatory, antioxidative, and neuroprotective properties.


Assuntos
Neuralgia , Neuropatia Ciática , Camundongos , Animais , Ácido Betulínico , Constrição , Fator 2 Relacionado a NF-E2 , Nervo Isquiático/lesões , Neuropatia Ciática/complicações , Neuropatia Ciática/tratamento farmacológico , Neuropatia Ciática/patologia , Citocinas/metabolismo , Hiperalgesia/metabolismo , Neuralgia/metabolismo , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Anti-Inflamatórios/farmacologia
15.
J Chem Neuroanat ; 133: 102327, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37634701

RESUMO

Neuropathic pain is a common symptom experienced by most clinical diseases at different levels, and its treatment has always been a clinical difficulty. Therefore, it is particularly important to explore new and effective treatment methods. The role of olfactory ensheathing cells (OECs) in nerve injury and pain is recognized by different studies. Our previous study found that transplantation of OECs alleviated hyperalgesia in rats. However, single-cell transplantation lacks medium adhesion and support, and exerts limited analgesic effect. Therefore, on the basis of the previous study, this study investigated the effect of pain relief by co-transplanting OECs with chitosan (CS) (a biological tissue engineering material, as OECs were transplanted into the host medium) to the injured sciatic nerve. The results showed that the pain threshold of sciatic nerve injury of rats was significantly reduced, and the expression level of P2×4 receptor in the spinal cord was significantly increased. While olfactory ensheathing cells combined with chitosan (OECs+CS) transplantation could significantly relieve pain, and the analgesic effect was stronger than that of OECs transplantation alone. OECs+CS transplantation promoted the formation of sciatic nerve remyelination, improved the changes of demyelination, and promoted the repair of sciatic nerve injury more significantly. In addition, the effect of OECs+CS to down-regulate the expression of P2×4 receptor was significantly stronger than that of OECs transplantation, and exerted a better analgesic effect. These data reveal that OECs+CS have a better analgesic effect in relieving neuropathic pain induced by sciatic nerve injury, and provide a new therapeutic strategy for pain treatment.


Assuntos
Quitosana , Neuralgia , Neuropatia Ciática , Traumatismos da Medula Espinal , Ratos , Animais , Materiais Biocompatíveis/metabolismo , Ratos Sprague-Dawley , Quitosana/farmacologia , Quitosana/uso terapêutico , Quitosana/metabolismo , Traumatismos da Medula Espinal/metabolismo , Neuropatia Ciática/metabolismo , Nervo Isquiático/fisiologia , Neuralgia/terapia , Neuralgia/metabolismo , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Analgésicos/metabolismo , Bulbo Olfatório/metabolismo , Regeneração Nervosa/fisiologia
16.
Brain Res ; 1819: 148542, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37604315

RESUMO

Paradoxically, while acute pain leads to transiently elevated corticosterone, chronic pain does not result in persistently elevated corticosterone. In the sciatic nerve chronic constriction injury (CCI) model of chronic pain, we have shown that the same nerve injury produces a range of behavioural outcomes, each associated with distinctive adaptations to the HPA-axis to achieve stable plasma corticosterone levels. We also demonstrated that CRF and GR expression in the paraventricular hypothalamus (PVH) was increased in rats that showed persistent changes to their social behaviours during Resident-Intruder testing ('Persistent Effect' rats) when compared to rats that showed no behavioural changes ('No Effect' rats). In this study, we investigated whether these changes were driven in part by altered sensitivity of the brainstem catecholaminergic pathways (known to regulate the PVH) to glucocorticoids. GR expression in adrenergic (C1,C2) and noradrenergic (A1,A2) cells was determined using immunohistochemistry in behaviourally tested CCI rats and in uninjured controls. We found no differences between Persistent Effect and No Effect rats in (1) the glucocorticoid sensitivity of these cells, or (2) the numbers of adrenergic and noradrenergic cells in each region. However, we discovered an overall reduction in GR expression in the non-catecholaminergic cells of these regions in both experimental groups when compared to uninjured controls, most likely attributable to the repeated Resident-Intruder testing. Taken together, these data suggest strongly that brainstem mechanisms are unlikely to play a key role in the rebalancing of the HPA-axis triggered by CCI, increasing the probability that these changes are driven by supra-hypothalamic regions.


Assuntos
Dor Crônica , Traumatismos dos Nervos Periféricos , Neuropatia Ciática , Ratos , Animais , Glucocorticoides/metabolismo , Receptores de Glucocorticoides/metabolismo , Ratos Sprague-Dawley , Corticosterona , Interação Social , Comportamento Animal/fisiologia , Neuropatia Ciática/metabolismo , Nervo Isquiático/lesões , Adrenérgicos
17.
J Neuroimmunol ; 382: 578156, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37556888

RESUMO

We reported a 61-year-old man presented with 10-month progressing left sciatic neuropathy and 10-day right facial neuropathy. Serum amphiphysin-IgG was positive. 18F-FDG PET/CT of the whole body showed no signs of malignancy. Treatment with plasma exchange and oral prednisone relieved the symptoms. Nine months later, right hemiparesis and seizure of right limbs developed. 18F-FDG and 18F-PBR06 (18 kDa translocator protein, TSPO) radioligand PET/MRI of the whole body revealed intense uptake in the intracranial lesions. Intracranial lymphoma was diagnosed by stereotactic needle brain biopsy. Mononeuropathies could be paraneoplastic syndromes. TSPO shows high uptake in intracranial lymphoma on 18F-PBR06 PET images.


Assuntos
Neoplasias do Sistema Nervoso Central , Doenças do Nervo Facial , Linfoma , Neuropatia Ciática , Humanos , Masculino , Pessoa de Meia-Idade , Encéfalo/imunologia , Doenças do Nervo Facial/etiologia , Doenças do Nervo Facial/imunologia , Doenças do Nervo Facial/terapia , Fluordesoxiglucose F18 , Imunoglobulina G/imunologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Receptores de GABA/metabolismo , Neuropatia Ciática/etiologia , Neuropatia Ciática/imunologia , Neuropatia Ciática/terapia , Neoplasias do Sistema Nervoso Central/complicações , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/imunologia , Doenças Autoimunes/etiologia , Doenças Autoimunes/imunologia , Linfoma/complicações , Linfoma/diagnóstico por imagem , Linfoma/imunologia , Polineuropatia Paraneoplásica/etiologia , Polineuropatia Paraneoplásica/imunologia , Prednisona/uso terapêutico , Glucocorticoides/uso terapêutico , Troca Plasmática , Proteínas do Tecido Nervoso/imunologia
18.
Neurosci Lett ; 814: 137419, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37558176

RESUMO

During the onset of neuropathic pain from a variety of etiologies, nociceptors become hypersensitized, releasing neurotransmitters and other factors from centrally-projecting nerve terminals within the dorsal spinal cord. Consequently, glial cells (astrocytes and microglia) in the spinal cord are activated and mediate the release of proinflammatory cytokines that act to enhance pain transmission and sensitize mechanical non-nociceptive fibers which ultimately results in light touch hypersensitivity, clinically observed as allodynia. Pramipexole, a D2/D3 preferring agonist, is FDA-approved for the treatment of Parkinson's disease and demonstrates efficacy in animal models of inflammatory pain. The clinical-stage investigational drug, R(+) enantiomer of pramipexole, dexpramipexole, is virtually devoid of D2/D3 agonist actions and is efficacious in animal models of inflammatory and neuropathic pain. The current experiments focus on the application of a mouse model of sciatic nerve neuropathy, chronic constriction injury (CCI), that leads to allodynia and is previously characterized to generate spinal glial activation with consequent release IL-1ß. We hypothesized that both pramipexole and dexpramipexole reverse CCI-induced chronic neuropathy in mice, and in human monocyte cell culture studies (THP-1 cells), pramipexole prevents IL-1ß production. Additionally, we hypothesized that in rat primary splenocyte culture, dexpramixole increases mRNA for the anti-inflammatory and pleiotropic cytokine, interleukin-10 (IL-10). Results show that following intravenous pramipexole or dexpramipexole, a profound decrease in allodynia was observed by 1 hr, with allodynia returning 24 hr post-injection. Pramipexole significantly blunted IL-1ß protein production from stimulated human monocytes and dexpramipexole induced elevated IL-10 mRNA expression from rat splenocytes. The data support that clinically-approved compounds like pramipexole and dexpramipexole support their application as anti-inflammatory agents to mitigate chronic neuropathy, and provide a blueprint for future, multifaceted approaches for opioid-independent neuropathic pain treatment.


Assuntos
Neuralgia , Traumatismos dos Nervos Periféricos , Neuropatia Ciática , Camundongos , Ratos , Humanos , Animais , Interleucina-10/metabolismo , Hiperalgesia/metabolismo , Pramipexol , Drogas em Investigação/metabolismo , Drogas em Investigação/uso terapêutico , Citocinas/metabolismo , Neuralgia/metabolismo , Neuropatia Ciática/metabolismo , Medula Espinal/metabolismo , Nervo Isquiático/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Técnicas de Cultura de Células
19.
Bioelectromagnetics ; 44(7-8): 192-203, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37464929

RESUMO

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.


Assuntos
Traumatismos dos Nervos Periféricos , Neuropatia Ciática , Ratos , Feminino , Animais , Nervo Isquiático , Ratos Wistar , Neuropatia Ciática/terapia , Traumatismos dos Nervos Periféricos/terapia , Estimulação Elétrica , Regeneração Nervosa/fisiologia , Células de Schwann
20.
Biochem Biophys Res Commun ; 674: 36-43, 2023 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-37393642

RESUMO

Peripheral nerve injuries have common clinical problems that are often accompanied by sensory and motor dysfunction and failure of axonal regeneration. Although various therapeutic approaches have been attempted, full functional recovery and axonal regeneration are rarely achieved in patients. In this study, we investigated the effects of recombinant adeno-associated virus (AAV) of mesencephalic astrocyte-derived neurotrophic factor (AAV-MANF) or placental growth factor (AAV-PlGF) transduced into mesenchymal stem cells (hMSC-MANF and hMSC-PlGF), which were then transplanted using human decellularized nerves (HDN) into sciatic nerve injury model. Our results showed that both AAV-MANF and AAV-PlGF were expressed in MSCs transplanted into the injury site. Behavioral measurements performed 2, 4, 6, 8, and 12 weeks after injury indicated that MANF facilitated the rapid and improved recovery of sensory and motor functions than PlGF. In addition, immunohistochemical analysis was used to quantitatively analyze the myelination of neurofilaments, Schwann cells, and regrowth axons. Both hMSC-MANF and hMSC-PlGF increased axon numbers and immunoreactive areas of axons and Schwann cells compared with the hMSC-GFP group. However, hMSC-MANF significantly improved the thickness of axons and Schwann cells compared with hMSC-PlGF. G-ratio analysis also showed a marked increase in axon myelination in axons thicker than 2.0 µm treated with MANF than that treated with PlGF. Our study suggests that transplantation of hMSC transduced with AAV-MANF has a potential to provide a novel and efficient strategy for promoting functional recovery and axonal regeneration in peripheral nerve injury.


Assuntos
Traumatismos dos Nervos Periféricos , Neuropatia Ciática , Humanos , Feminino , Traumatismos dos Nervos Periféricos/metabolismo , Recuperação de Função Fisiológica/fisiologia , Astrócitos/metabolismo , Regeneração Nervosa/fisiologia , Fator de Crescimento Placentário/metabolismo , Neuropatia Ciática/metabolismo , Axônios/metabolismo , Fatores de Crescimento Neural/metabolismo , Células de Schwann/metabolismo , Nervo Isquiático/metabolismo
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