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1.
Eur Rev Med Pharmacol Sci ; 28(7): 2654-2661, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38639504

RESUMO

OBJECTIVE: This study aimed to explore the effect of flipped venous catheters combined with spinal cord electrical stimulation on functional recovery in patients with sciatic nerve injury. PATIENTS AND METHODS: 160 patients with hip dislocation and sciatic nerve injury were divided into conventional release and flipped catheter + electrical stimulation groups according to the treatment methods (n=80). Motor nerve conduction velocity (MCV) and lower limb motor function were compared. Serum neurotrophic factors brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were compared. The frequency of complications and quality of life were also compared. RESULTS: The MCV levels of the common peroneal nerve and tibial nerve in the flipped catheter + electrical stimulation group were greater than the conventional lysis group (p<0.05). After treatment, the lower extremity motor score (LMEs) in the flipped catheter + electrical stimulation group was greater than the conventional lysis group (p<0.05). The serum levels of BDNF and NGF in the flip catheter + electrical stimulation group were higher than the conventional lysis group (p<0.05). The complication rate in the flipped catheter + electrical stimulation group was lower than in the conventional release group (6.25% vs. 16.25%, p<0.05). The quality-of-life score in the flip catheter + electrical stimulation group was greater than the conventional lysis group (p<0.05). CONCLUSIONS: The flipped venous catheter combined with spinal cord electrical stimulation can improve nerve conduction velocity, lower limb motor function, serum BDNF and NGF levels, reduce complications, and help improve the quality of life of sufferers with sciatic nerve injury. Chictr.org.cn ID: ChiCTR2400080984.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Neuropatia Ciática , Ratos , Animais , Humanos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ratos Sprague-Dawley , Fator de Crescimento Neural/metabolismo , Qualidade de Vida , Neuropatia Ciática/metabolismo , Neuropatia Ciática/terapia , Medula Espinal/metabolismo , Nervo Isquiático , Cateteres , Estimulação Elétrica/métodos
2.
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
3.
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
4.
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
5.
Acta Cir Bras ; 37(8): e370804, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36327398

RESUMO

PURPOSE: Various postoperative protocols have been proposed to improve outcomes and accelerate nerve regeneration. Recently, the use of physical exercise in a post-surgical neurorraphy procedure has shown good results when started early. We experimentally investigated the hypothesis that post-operative exercise speeds up results and improves clinical and morphologic parameters. METHODS: Isogenic rats were randomly divided into four groups: 1 SHAM; 2 SHAM submitted to the exercise protocol (EP); 3 Grafting of the sciatic nerve; and 4 Grafting of the sciatic nerve associated with the EP. The EP was based on aerobic activities with a treadmill, with a progressive increase in time and intensity during 6 weeks. The results were evaluated by the sciatic functional index (SFI), morphometric and morphologic analysis of nerve distal to the lesion, and the number of spinal cord motor neurons, positive to the marker Fluoro-Gold (FG), captured retrogradely through neurorraphy. RESULTS: Functional analysis (SFI) did not show a statistical difference between the group grafted with (-50.94) and without exercise (-65.79) after 90 days. The motoneurons count (Spinal cord histology) also showed no diference between these groups (834.5 × 833 respectively). Although functionally there is no difference between these groups, morphometric study showed a greater density (53.62) and larger fibers (7.762) in GRAFT group. When comparing both operated groups with both SHAM groups, all values were much lower. CONCLUSIONS: The experimental model that this aerobic treadmill exercises protocol did not modify nerve regeneration after sciatic nerve injury and repair with nerve graft.


Assuntos
Regeneração Nervosa , Traumatismos dos Nervos Periféricos , Condicionamento Físico Animal , Neuropatia Ciática , Animais , Ratos , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/cirurgia , Traumatismos dos Nervos Periféricos/terapia , Ratos Endogâmicos SHR , Nervo Isquiático/lesões , Nervo Isquiático/transplante , Neuropatia Ciática/cirurgia , Neuropatia Ciática/terapia
6.
Neurosci Lett ; 787: 136812, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-35872241

RESUMO

Resistance training improves muscle strength through a combination of neural plasticity and muscle hypertrophy. This study aimed to evaluate the effects of resistance exercise on sciatic nerve regeneration and histology, growth-associated protein 43 (GAP-43) expressions, and soleus muscle atrophy following traumatic nerve injuries in Wistar rats. In the present study, 40 male Wistar rats were randomly assigned into four groups: healthy control (HC) as a sham group was exposed to the surgical procedures without any sciatic nerve compression, lesioned control (LC), resistance training (RT,non-lesioned), and lesioned rats + RT (LRT) (n = 10 in each). The RT group performed a resistance-training program 5 days/week for 4 weeks. Sciatic functional index (SFI) score, beam score and Basso, Beattie, and Bresnahan (BBB) score decreased and the hot plate time increased significantly in the LC| group compared to the HC (p < 0.05) group. However, the LRT| group showed a significant increase in the SFI score (p = 0.001) and a significant decrease in hot plate time (p = 0.0232) compared to the LC group. The LC group also showed neurological morphological damage and muscle atrophy and a decrease in GAP-43 in nerve tissue. In comparison to the LC group, a significant increase in sciatic nerve caliber, diameter, number of muscle fibers, and the expression of GAP-43| (p < 0.05) was observed in the LRT group. Doing resistance training even for four weeks seems to affect sciatic nerve lesions and injuries. It can also repair and regenerate nerve tissue by upregulating GAP-43 expression|, improving motor behavioral tests, and controlling muscle atrophy.


Assuntos
Proteína GAP-43 , Atrofia Muscular , Regeneração Nervosa , Condicionamento Físico Animal , Treinamento de Força , Neuropatia Ciática , Animais , Modelos Animais de Doenças , Proteína GAP-43/metabolismo , Humanos , Masculino , Músculo Esquelético/inervação , Atrofia Muscular/terapia , Tecido Nervoso , Ratos , Ratos Wistar , Nervo Isquiático/lesões , Neuropatia Ciática/terapia
7.
Pan Afr Med J ; 39: 188, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34584613

RESUMO

The injury caused due to the intramuscular (IM) mode of drug administration are still affecting population in rural area more than urban area. The IM injection given in any quadrant except the upper outer quadrant of buttock most commonly damages the sciatic nerve because of its course and extent in the injection prone site. The iatrogenic sciatic nerve injury because of IM injection in dorsogluteal site is a matter of concern all over the world covering the undeveloped, developing and developed countries. The iatrogenic sciatic neuritis causes severe neurological or motor deficits leading to the medico-legal consequences. An 8-year-old male child, post dorsogluteal IM injection for mild fever and cold, presented left lower limb weakness and pain in left gluteal region. The patient underwent the medical and physiotherapeutic management for 14 months. The medical management included the initial dose of steroids and ox carbamazepine along with methylcobalamine and folic acid. The physiotherapeutic intervention concentrated on the functional independency of child. The patient attended complete physiological and functional recovery by the end of 14th month concluding that sometimes waiting for lesion to resolve is better than intervention. The iatrogenic sciatic neuritis is a complication that needs attention for prevention following intramuscular drug administration technique.


Assuntos
Injeções Intramusculares/efeitos adversos , Nervo Isquiático/lesões , Neuropatia Ciática/etiologia , Nádegas , Criança , Terapia Combinada , Seguimentos , Humanos , Masculino , Modalidades de Fisioterapia , Recuperação de Função Fisiológica , Neuropatia Ciática/terapia
8.
BMC Neurosci ; 22(1): 50, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384370

RESUMO

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


Assuntos
Fator Neurotrófico Derivado do Encéfalo/administração & dosagem , Ouro/administração & dosagem , Células-Tronco Mesenquimais , Nanopartículas Metálicas/administração & dosagem , Regeneração Nervosa/fisiologia , Neuropatia Ciática/terapia , Animais , Terapia Combinada , Sistemas de Liberação de Medicamentos/métodos , Quimioterapia Combinada , Fibrina/administração & dosagem , Masculino , Regeneração Nervosa/efeitos dos fármacos , Ratos , Ratos Wistar , Neuropatia Ciática/patologia , Neuropatia Ciática/fisiopatologia
9.
Int J Mol Sci ; 22(14)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34299065

RESUMO

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


Assuntos
Gânglios Espinais/citologia , Imunidade Inata/imunologia , Neurônios/citologia , Neurônios/imunologia , Fator de Transcrição STAT3/metabolismo , Neuropatia Ciática/terapia , Receptor Toll-Like 9/metabolismo , Animais , Masculino , Ratos , Ratos Wistar , Fator de Transcrição STAT3/genética , Neuropatia Ciática/imunologia , Neuropatia Ciática/metabolismo , Neuropatia Ciática/patologia , Receptor Toll-Like 9/genética
10.
Neurotox Res ; 39(5): 1470-1486, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34309780

RESUMO

Nowadays, researchers pay a vast deal of attention to neural tissue regeneration due to its tremendous effect on the patient's life. There are many strategies, from using conventional autologous nerve grafts to the newly developed methods for reconstructing damaged nerves. Among the various therapeutic methods, incorporating highly potent biomolecules and growth factors, the damaged nerve site would promote nerve regeneration. The aim was to examine the efficiency of a mesenchymal stem cell condition medium (MSC-CM) loaded on a 3D-polycaprolactone (PCL) scaffold as a nerve conduit in an axotomy rat model. Twenty-four mature male rats were classified into four groups: controls (the animals of this group were intact), axotomy (10 mm piece of the nerve was removed), axotomy (10-mm piece of the nerve was removed) + scaffold, and axotomy (10-mm piece of the nerve was removed) + MSC-CM-loaded scaffold. We followed up nerve motor function using a sciatic function index and electromyography activity of the gastrocnemius muscle. At 12 weeks post axotomy, sciatic nerve and dorsal root ganglion specimens and L4 and L5 spinal cord segments were separated from the rats and were analyzed by stereological, immunohistochemistry, and RT-PCR procedures. The rats of the axotomy group presented the expected gross locomotor deficit. Stereological parameters, immunohistochemistry of GFAP, and gene expression of S100, NGF, and BDNF were significantly enhanced in the CM-loaded scaffold group compared with the axotomy group. The most observed similarity was noted between the results of the control group and the CM-loaded scaffold group. Our results support the potential applicability of MSC-CM-loaded PCL nanofibrous scaffold to treat peripheral nerve injury (PNI).


Assuntos
Meios de Cultivo Condicionados/farmacologia , Células-Tronco Mesenquimais/fisiologia , Nanofibras/administração & dosagem , Regeneração Nervosa/fisiologia , Poliésteres/administração & dosagem , Neuropatia Ciática/terapia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Masculino , Camundongos , Regeneração Nervosa/efeitos dos fármacos , Ratos , Ratos Wistar , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Nervo Isquiático/fisiologia , Neuropatia Ciática/patologia , Tecidos Suporte
11.
J Musculoskelet Neuronal Interact ; 21(1): 68-78, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33657756

RESUMO

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


Assuntos
Regeneração Nervosa/fisiologia , Nervos Periféricos/fisiologia , Recuperação de Função Fisiológica/fisiologia , Neuropatia Ciática/terapia , Vibração/uso terapêutico , Animais , Masculino , Ratos , Ratos Wistar , Neuropatia Ciática/patologia , Neuropatia Ciática/fisiopatologia
12.
J Neurosci Res ; 99(2): 545-560, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33070351

RESUMO

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


Assuntos
Tecido Adiposo/citologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/terapia , Nervos Periféricos/fisiologia , Animais , Diferenciação Celular , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/metabolismo , Fatores de Crescimento Neural/metabolismo , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Traumatismos dos Nervos Periféricos/cirurgia , Coelhos , Ratos , Células de Schwann/fisiologia , Células de Schwann/transplante , Neuropatia Ciática/cirurgia , Neuropatia Ciática/terapia , Engenharia Tecidual , Tecidos Suporte , Transplante Autólogo
13.
J Mater Chem B ; 8(48): 11063-11073, 2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33200763

RESUMO

Reconstruction of peripheral nerve defects with tissue engineered nerve scaffolds is an exciting field of biomedical research and holds potential for clinical application. However, due to poor neovascularization after the implantation, nerve regeneration is still not satisfactory, especially for large nerve defects. These obstacles hinder the investigation of basic neurobiological principles and development of a wide range of treatments for peripheral nerve diseases. Herein, we designed an amphiphilic alternating block polyurethane (abbreviated as PU) copolymer-based nerve guidance scaffold, which has good Schwann cell compatibility, and more importantly, a rapid vascularization of the scaffold in vivo. In the sciatic nerve transection model of SD rats, vascularized PU nerve guidance scaffolds induced rapid regeneration of nerve fibers and axons along the scaffold. Through the analysis of nerve electrophysiology, sciatic nerve functional index, histology, and immunofluorescence related to angiogenesis, we determined that PU with rapid vascularization function enhances recovery and re-obtains nerve conduction function. Our study points out a new strategy of using nerve tissue engineering scaffolds to treat large nerve defects.


Assuntos
Implantes Absorvíveis , Aloenxertos Compostos/metabolismo , Regeneração Tecidual Guiada/métodos , Poliuretanos/metabolismo , Neuropatia Ciática/metabolismo , Tecidos Suporte , Animais , Células Cultivadas , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/fisiologia , Poliuretanos/administração & dosagem , Ratos , Ratos Sprague-Dawley , Procedimentos de Cirurgia Plástica/métodos , Neuropatia Ciática/terapia , Engenharia Tecidual/métodos
14.
J Neurosci Res ; 98(12): 2468-2495, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32931034

RESUMO

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


Assuntos
Imunidade Adaptativa/fisiologia , Imunidade Inata/fisiologia , Polietilenoglicóis/administração & dosagem , Nervo Isquiático/imunologia , Nervo Isquiático/transplante , Neuropatia Ciática/terapia , Imunidade Adaptativa/efeitos dos fármacos , Aloenxertos/imunologia , Aloenxertos/transplante , Animais , Feminino , Imunidade Inata/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Neuropatia Ciática/imunologia , Transplante Homólogo/métodos
15.
Rev Chil Pediatr ; 91(1): 85-93, 2020 Feb.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32730417

RESUMO

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


Assuntos
Neuropatia Ciática/diagnóstico , Adolescente , Criança , Pré-Escolar , Eletromiografia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neuropatia Ciática/etiologia , Neuropatia Ciática/fisiopatologia , Neuropatia Ciática/terapia
16.
Neurochem Res ; 45(9): 2065-2071, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32529390

RESUMO

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


Assuntos
Encefalinas/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Neuralgia/terapia , Precursores de Proteínas/uso terapêutico , Animais , Engenharia Celular , Encefalinas/genética , Técnicas de Transferência de Genes , Terapia Genética , Humanos , Masculino , Precursores de Proteínas/genética , Ratos Sprague-Dawley , Nervo Isquiático/lesões , Neuropatia Ciática/terapia
17.
PLoS One ; 15(5): e0233531, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32453807

RESUMO

Several studies have investigated the use of invasive and non-invasive stimulation methods to enhance nerve regeneration, and varying degrees of effectiveness have been reported. However, due to the use of different parameters in these studies, a fair comparison between the effectiveness of invasive and non-invasive stimulation methods is not possible. The present study compared the effectiveness of invasive and non-invasive stimulation using similar parameters. Eighteen Sprague Dawley rats were classified into three groups: the iES group stimulated with fully implantable device, the tES group stimulated with transcutaneous electrical nerve stimulation (TENS), and the injury group (no stimulation). The iES and tES groups received stimulation for 6 weeks starting immediately after the injury. Motor function was evaluated using the sciatic functional index (SFI) every week. The SFI values increased over time in all groups; faster and superior functional recovery was observed in the iES group than in the tES group. Histological evaluation of the nerve sections and gastrocnemius muscle sections were performed every other week. The axon diameter and muscle fiber area in the iES group were larger, and the g-ratio in the iES group was closer to 0.6 than those in the tES group. To assess the cause of the difference in efficiency, a 3D rat anatomical model was used to simulate the induced electric fields in each group. A significantly higher concentration and intensity around the sciatic nerve was observed in the iES group than in the tES group. Vector field distribution showed that the field was orthogonal to the sciatic nerve spread in the tES group, whereas it was parallel in the iES group; this suggested that the tES group was less effective in nerve stimulation. The results indicated that even though rats in the TENS group showed better recovery than those in the injury group, it cannot replace direct stimulation yet because rats stimulated with the invasive method showed faster recovery and superior outcomes. This was likely attributable to the greater concentration and parallel distribution of electric field with respect to target nerve.


Assuntos
Lesões por Esmagamento/terapia , Regeneração Nervosa/fisiologia , Neuropatia Ciática/terapia , Estimulação Elétrica Nervosa Transcutânea , Animais , Axônios/efeitos da radiação , Lesões por Esmagamento/fisiopatologia , Lesões por Esmagamento/cirurgia , Modelos Animais de Doenças , Humanos , Fibras Musculares Esqueléticas/fisiologia , Fibras Musculares Esqueléticas/efeitos da radiação , Músculo Esquelético/fisiopatologia , Músculo Esquelético/efeitos da radiação , Compressão Nervosa/métodos , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia , Nervo Isquiático/crescimento & desenvolvimento , Nervo Isquiático/fisiopatologia , Nervo Isquiático/cirurgia , Neuropatia Ciática/fisiopatologia , Neuropatia Ciática/cirurgia
18.
Muscle Nerve ; 62(1): 119-127, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32243602

RESUMO

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


Assuntos
Tecido Adiposo/fisiologia , Diferenciação Celular/fisiologia , Regeneração Nervosa/fisiologia , Células de Schwann/fisiologia , Nervo Isquiático/fisiologia , Transplante de Células-Tronco/métodos , Tecido Adiposo/citologia , Tecido Adiposo/transplante , Animais , Diferenciação Celular/efeitos dos fármacos , Colágeno/administração & dosagem , Feminino , Regeneração Nervosa/efeitos dos fármacos , Nervos Periféricos/efeitos dos fármacos , Nervos Periféricos/fisiologia , Ácido Poliglicólico/administração & dosagem , Ratos , Ratos Wistar , Células de Schwann/transplante , Nervo Isquiático/efeitos dos fármacos , Neuropatia Ciática/fisiopatologia , Neuropatia Ciática/terapia , Células-Tronco/fisiologia
19.
Muscle Nerve ; 61(6): 815-825, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32170960

RESUMO

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


Assuntos
Imunomodulação/fisiologia , Imageamento por Ressonância Magnética/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Neuropatia Ciática/diagnóstico por imagem , Traumatismos do Sistema Nervoso/diagnóstico por imagem , Animais , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Neuropatia Ciática/imunologia , Neuropatia Ciática/terapia , Traumatismos do Sistema Nervoso/imunologia , Traumatismos do Sistema Nervoso/terapia
20.
Rev. chil. pediatr ; 91(1): 85-93, feb. 2020. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1092791

RESUMO

Resumen: Introducción: La neuropatía ciática es una entidad infrecuente y de difícil diagnóstico en Pediatría. Su evolución a largo plazo no ha sido claramente definida. Objetivo: Analizar la presentación clínica y evolución de un grupo de niños con neuropatía ciática. Pacientes y Método: Análisis retrospectivo de las características clínicas de pacientes pediátricos con neuropatía ciática atendidos en 2 hospitales de Santiago, entre 2014-2018. Se evaluó examen motor, trofismo muscular, reflejos osteotendíneos, marcha, sensibilidad y dolor. Se estudió neuroconducción de nervio ciático, electromiografía (EMG) y en 3 pacientes, Resonancia Magnética (RM). Resultados: Se incluyeron 6 pacientes, edad promedio 11,8 años. Hubo 2 causas traumáticas, 2 compresivas, 1 vascular y 1 tumoral. Los 6 pa cientes debutaron con pie caído e hiporreflexia/arreflexia aquiliana; 5 pacientes presentaron dolor neuropático severo. La EMG mostró en todos los casos compromiso en nervios y musculatura de pendientes del nervio ciático. En 2 casos se realizó RM de cintura pélvica y extremidades inferiores, mostrando compromiso muscular selectivo en pierna en territorio ciático. En 1 caso, se realizó RM de plexo lumbosacro, y luego estudio histológico, que concluyeron un tumor neural benigno. En los 3 pacientes que tuvieron seguimiento mayor a un año, se observaron secuelas motoras, con marcha alterada. Conclusión: La neuropatía ciática en este grupo fue secundaria a diversas etiologías, predominando las traumático-compresivas. En los 3 casos que tuvieron seguimiento a largo plazo se observaron secuelas motoras significativas. En la mayoría la lesión se asoció a causas prevenibles como accidentes y posicionamiento en niños con compromiso de conciencia, lo que resulta fundamental en la prevención de una patología con alto grado de secuelas.


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


Assuntos
Humanos , Feminino , Pré-Escolar , Criança , Adolescente , Neuropatia Ciática/diagnóstico , Prognóstico , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Fatores de Risco , Seguimentos , Neuropatia Ciática/etiologia , Neuropatia Ciática/fisiopatologia , Neuropatia Ciática/terapia , Eletromiografia
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