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1.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(1): 59-68, 2020 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-32037768

RESUMO

OBJECTIVE: To systematically evaluate the repairing effect of stem cells on facial nerve defects. METHODS: Articles regarding the regenerating effect of stem cells on facial nerves in animals were collected from the databases of Pubmed, Cochrane Library, Web of Science, Embase, Scopus, and CBM. Two professionals independently completed the article screening, data extraction, and bias risk assessment. RevMan 5.3 and random-effects models were used for the statistical analysis, and the results were presented in the form of mean differences (MD) with a 95%CI. The results of functional evaluation (vibrissae movement, facial paralysis) and histological evaluation (density of myelinated fibers, diameter of fibers, thickness of myelin sheath, G ratio) of facial nerve were Meta-analyzed. RESULTS: A total of 4 614 articles were retrieved from the 6 databases, and 15 of these articles were included in the Meta-analysis. For vibrissae movement and facial paralysis, the stem cell group scored significantly higher than the non-stem cell group (P<0.05). The density of myelinated fibers and thickness of the myelin sheath in the stem cell group were higher than those in the non-stem cell group (P<0.05). The G ratio in the stem cell group was smaller than that in the non-stem cell group (P=0.001). There was no significant difference in fiber diameter (P=0.08). CONCLUSIONS: Stem cells have potential in promoting facial nerve regeneration.


Assuntos
Nervo Facial , Paralisia Facial , Animais , Regeneração Nervosa , Células-Tronco , Vibrissas
2.
Plast Reconstr Surg ; 145(2): 368e-381e, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31985643

RESUMO

BACKGROUND: Acellular nerve allografts are a viable treatment modality for bridging nerve gaps. Several small studies have demonstrated results equal to those of autologous grafts; however, there is information lacking with regard to outcomes for wider indications. The authors evaluated the outcomes of patients treated with a nerve allograft in a variety of clinical situations. METHODS: A retrospective chart analysis was completed between April of 2009 and October of 2017. Inclusion criteria were age 18 years or older at the time of surgery and treatment with a nerve allograft. Patients were excluded if they had not been followed up for a minimum of 6 months. The modified Medical Research Council Classification was used to monitor motor and sensory changes in the postoperative period. RESULTS: Two hundred seven nerve allografts were used in 156 patients; of these, 129 patients with 171 nerve allografts fulfilled the inclusion criteria. Seventy-seven percent of patients achieved a sensory outcome score of S3 or above and 36 percent achieved a motor score of M3 or above. All patients with chronic pain had improvement of their symptoms. Graft length and diameter were negatively correlated with reported outcomes. One patient elected to undergo revision surgery, and the original graft was shown histologically to have extensive central necrosis. Anatomically, allografts used for lower limb reconstruction yielded the poorest results. All chronic patients had a significantly lower postoperative requirement for analgesia, and allografts were effective in not only reducing pain but also restoring a functional level of sensation. CONCLUSIONS: This study supports the wider application of allografts in managing nerve problems. However, caution must be applied to the use of long grafts with larger diameters. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Assuntos
Traumatismos dos Nervos Periféricos/cirurgia , Nervos Periféricos/transplante , Procedimentos Cirúrgicos Reconstrutivos/métodos , Adulto , Idoso , Aloenxertos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Regeneração Nervosa/fisiologia , Neuralgia/cirurgia , Estudos Retrospectivos , Adulto Jovem
3.
Gene ; 724: 144151, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31626959

RESUMO

BACKGROUND: Differentiation of mesenchymal stem cells (MSCs) into Schwann-like cells onto processed nerve allografts may support peripheral nerve repair. The purpose of this study was to understand the biological characteristics of undifferentiated and differentiated MSCs before and after seeding onto a processed nerve allograft by comparing gene expression profiles. METHODS: MSCs from Lewis rats were cultured in maintenance media or differentiated into Schwann-like cells. Both treatment groups were dynamically seeded onto decellularized nerve allografts derived from Sprague-Dawley rats. Gene expression was quantified by quantitative polymerase chain reaction (qPCR) analysis of representative biomarkers, including neurotrophic (GDNF, PTN, GAP43, PMP22), angiogenic (CD31, VEGF1), extracellular matrix (ECM) (COL1A1, COL3A1, FBLN1, LAMB2) or cell cycle (CAPS3, CCBN2) genes. Gene expression values were statistically evaluated using a 2-factor ANOVA with repeated measures. RESULTS: Baseline gene expression of undifferentiated and differentiated MSCs was significantly altered upon interaction with processed nerve allografts. Interaction between processed allografts and undifferentiated MSCs enhanced expression of neurotrophic (NGF, GDNF, PMP22), ECM (FBLN1, LAMB2) and regulatory cell cycle genes (CCNB2) during a 7-day time course. Interactions of differentiated MSCs with nerve allografts enhanced expression of neurotrophic (NGF, GDNF, GAP43), angiogenic (VEGF1), ECM (FBLN1) and regulatory cell cycle genes (CASP3, CCNB2) within one week. CONCLUSIONS: Dynamic seeding onto processed nerve allografts modulates temporal gene expression profiles of differentiated and undifferentiated MSCs. These changes in gene expressions may support the reparative functions of MSCs in supporting nerve regeneration in different stages of axonal growth.


Assuntos
Diferenciação Celular/genética , Células-Tronco Mesenquimais/citologia , Nervo Isquiático/transplante , Transcriptoma , Tecido Adiposo/citologia , Aloenxertos , Animais , Técnicas de Cultura de Células/métodos , Matriz Extracelular/genética , Células-Tronco Mesenquimais/fisiologia , Neovascularização Fisiológica/genética , Regeneração Nervosa , Ratos Endogâmicos Lew , Ratos Sprague-Dawley , Células de Schwann/citologia , Nervo Isquiático/citologia , Fatores de Tempo , Transplante Homólogo
4.
Nihon Yakurigaku Zasshi ; 154(6): 340-344, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31787687

RESUMO

Central nervous system (CNS) inflammation causes severe neurological dysfunction, such as motor, sensory, and cognitive impairments. One of the reasons for the developing disease depends on the damage of neuronal network, a predominant feature of many CNS diseases. Therefore, protection and/or regeneration of damaged neuronal network after injury is considered to be useful for treating neurological diseases; however, the mechanism of protection and regeneration of neuronal network is not fully elucidated. In this paper, I describe our recent findings about the mechanism that disrupt and regenerate neuronal network by using animal model of multiple sclerosis. I also introduce the key molecules which is involved in inflammation, neurovascular interaction, and systemic regulation. These findings have a potential to contribute develop the new therapies for treating neurological disease.


Assuntos
Doenças do Sistema Nervoso Central/patologia , Sistema Nervoso Central/fisiopatologia , Regeneração Nervosa , Animais , Humanos , Inflamação/patologia , Esclerose Múltipla , Neurônios/patologia
5.
Georgian Med News ; (295): 145-152, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31804218

RESUMO

The work aims at studying the effect of the autologous bone marrow aspirate concentrate on regeneration of the sciatic nerve and atrophy of m. tibialis cranialis. We have simulated autografting of the sciatic nerve in rabbits with application of bone marrow aspirate concentrate around the graft area. We obtained autologous aspirate (2mL) from the proximal part of the femur, added dextrosecitrate (1:8), centrifuged it, and added 0.1 of bovine thrombine to 1.0 mL of supraerythrocytic fraction to obtain gel. On days 30 and 90 we assessed the rate of the sciatic nervere generation and morphological changes of the m.tibialis cranialis as well as the content of products of oxidative modification of lipids and proteins (TBA-active products, diene conjugates and carbonyl groups, respectively) and activity of antioxidant enzymatic system (catalase, glutathion peroxidase, glutathione reductase) in this muscle. Evaluation of the nerve fibers regeneration through the sciatic nerve graft 1 cm long showed that 16.0% of them had regenerated into the graft by day 30 and 60.3% by day 90, with 34.7% having regenerated into the distal stump. Application of bone marrow aspirate concentrate had significantly increased regeneration by day 30, amounting to 31.9% in the graft and up to 8.7% in the distal stump and up to 68.0% and 60.1% by day 90 respectively. Prolonged nerve regeneration resulted in progressive muscle atrophy, with decrease of muscular fibers content up to 68.2% and 27.8%. In the group with aspirate concentrate hypothrophy was delayed (% of muscle fibers being 82.8% and57.2%). The content of peroxidation products has dramatically increased by day 30 and has decreased by day 90 with activation of glutathione peroxidase and glutathione reductase enzymes (with catalase activity being significantly high in all the terms).We have also observed decreased oxidative modification of lipids and proteins in the aspirate concentrate group, with additional increase of glutathione peroxidase activity demonstrating the supportive effect of the aspirate cells.


Assuntos
Medula Óssea , Regeneração Nervosa , Nervo Isquiático , Animais , Bovinos , Glutationa Peroxidase , Coelhos , Nervo Isquiático/transplante , Transplante Autólogo
6.
J Enzyme Inhib Med Chem ; 34(1): 712-727, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852270

RESUMO

The design of multi-target directed ligands (MTDLs) is a valid approach for obtaining effective drugs for complex pathologies. MTDLs that combine neuro-repair properties and block the first steps of neurotoxic cascades could be the so long wanted remedies to treat neurodegenerative diseases (NDs). By linking two privileged scaffolds with well-known activities in ND-targets, the flavonoid and the N,N-dibenzyl(N-methyl)amine (DBMA) fragments, new CNS-permeable flavonoid - DBMA hybrids (1-13) were obtained. They were subjected to biological evaluation in a battery of targets involved in Alzheimer's disease (AD) and other NDs, namely human cholinesterases (hAChE/hBuChE), ß-secretase (hBACE-1), monoamine oxidases (hMAO-A/B), lipoxygenase-5 (hLOX-5) and sigma receptors (σ1R/σ2R). After a funnel-type screening, 6,7-dimethoxychromone - DBMA (6) was highlighted due to its neurogenic properties and an interesting MTD-profile in hAChE, hLOX-5, hBACE-1 and σ1R. Molecular dynamic simulations showed the most relevant drug-protein interactions of hybrid 6, which could synergistically contribute to neuronal regeneration and block neurodegeneration.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Metilaminas/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Acetilcolinesterase/metabolismo , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Araquidonato 5-Lipoxigenase/metabolismo , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Ácido Aspártico Endopeptidases/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Butirilcolinesterase/metabolismo , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Flavonoides/química , Humanos , Masculino , Metilaminas/química , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Moleculares , Estrutura Molecular , Monoaminoxidase/metabolismo , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química
7.
Nat Rev Neurol ; 15(12): 732-745, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31728042

RESUMO

Over the past decade, we have witnessed a flourishing of novel strategies to enhance neuroplasticity and promote axon regeneration following spinal cord injury, and results from preclinical studies suggest that some of these strategies have the potential for clinical translation. Spinal cord injury leads to the disruption of neural circuitry and connectivity, resulting in permanent neurological disability. Recovery of function relies on augmenting neuroplasticity to potentiate sprouting and regeneration of spared and injured axons, to increase the strength of residual connections and to promote the formation of new connections and circuits. Neuroplasticity can be fostered by exploiting four main biological properties: neuronal intrinsic signalling, the neuronal extrinsic environment, the capacity to reconnect the severed spinal cord via neural stem cell grafts, and modulation of neuronal activity. In this Review, we discuss experimental evidence from rodents, nonhuman primates and patients regarding interventions that target each of these four properties. We then highlight the strengths and challenges of individual and combinatorial approaches with respect to clinical translation. We conclude by considering future developments and providing views on how to bridge the gap between preclinical studies and clinical translation.


Assuntos
Regeneração Nervosa/fisiologia , Plasticidade Neuronal/fisiologia , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/metabolismo , Pesquisa Médica Translacional/métodos , Animais , Axônios/fisiologia , Humanos , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/genética
8.
Adv Exp Med Biol ; 1101: 91-122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31729673

RESUMO

Peripheral nervous system, widely spread in the whole body, is the important bridge for the transmission of neural signals. Signals from the central nervous system (brain and spinal cord) are transmitted to different parts of the body by the peripheral nerves, while along the way they also feedback all kinds of sensory information. Certain level of information integration and processing also occurs in the system. It has been shown that neural signals could be extracted from the distal end of the stump, indicating that the bridge is still effective after limb damage or amputation, which is the neurophysiological basis for the research and development of peripheral nerve interface for the prosthetic system.


Assuntos
Nervos Periféricos , Transdução de Sinais , Sistema Nervoso Central , Humanos , Regeneração Nervosa , Nervos Periféricos/fisiologia , Próteses e Implantes , Medula Espinal
9.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(11): 1439-1445, 2019 Nov 15.
Artigo em Chinês | MEDLINE | ID: mdl-31650763

RESUMO

Objective: To explore a green route for the fabrication of thermo-sensitive chitosan nerve conduits, improve the mechanical properties and decrease the degradation rate of the chitosan nerve conduits. Methods: Taking advantage of the ionic specific effect of the thermo-sensitive chitosan, the strengthened chitosan nerve conduits were obtained by immersing the gel-casted conduits in salt solution for ion-induced phase transition, and rinsing, lyophilization, and 60Co sterilization afterwards. The nerve conduits after immersing in NaCl solutions for 0, 4, 12, 24, 36, 48, and 72 hours were obtained and characterized the general observation, diameters and mechanical properties. According to the above results, the optimal sample was chosen and characterized the microstructure, degradation properties, and cytocompatibility. The left sciatic nerve defect 15 mm in length was made in 20 male Sprague Dawley rats. The autologous nerves (control group, n=10) and the nerve conduits (experimental group, n=10) were used to repair the defects. At 8 weeks after operation, the compound muscle action potential (CMAP) was measured. The regenerated nerves were investigated by gross observation and toluidine blue staining. The gastrocnemius muscle was observed by HE staining. Results: With the increased ionic phase transition time, the color of the conduit was gradually deepened and the diameter was gradually decreased, which showed no difference during 12 hours. The tensile strength of the nerve conduit was increased gradually. The ultimate tensile strength showed significant difference between the 48 hours and 12, 24, and 36 hours groups ( P<0.05), and no significant difference between the 48 hours and 72 hours groups ( P>0.05). As a result, the nerve conduit after ion-induced phase transition for 48 hours was chosen for further study. The scanning electron microscope (SEM) images showed that the nerve conduit had a uniform porous structure. The degradation rate of the the nerve conduit after ion-induced phase transition for 48 hours was significantly decreased as compared with that of the conduit without ion-induced phase transition. The nerve conduit could support the attachment and proliferation of rat Schwann cells on the inner surface. The animal experiments showed that at 8 weeks after operation, the CMAPs of the experimental and control groups were (3.5±0.9) and (4.3±1.1) m/V, respectively, which showed no significant difference between the two groups ( P<0.05), and were significantly lower than that of the contralateral site ï¼»(45.6±5.6 m/V), P>0.05ï¼½. The nerve conduit of the experimental group could repair the nerve defect. There was no significant difference between the experimental and control groups in terms of the histomorphology of the regenerated nerve fibers and the gastrocnemius muscle. Conclusion: The green route for the fabrication of thermo-sensitive chitosan nerve conduits is free of any toxic reagents, and has simple steps, which is beneficial to the industrial transformation of the chitosan nerve conduit products. The prepared chitosan nerve conduit can be applied to rat peripheral nerve defect repair and nerve tissue engineering.


Assuntos
Quitosana , Tecido Nervoso , Animais , Química Verde , Masculino , Regeneração Nervosa , Ratos , Ratos Sprague-Dawley , Nervo Isquiático
10.
Zhen Ci Yan Jiu ; 44(10): 777-80, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31657171

RESUMO

Astrocytes are the most abundant cells in the central nervous system, which has been demonstrated to be one of the targets for the treatment of ischemic stroke. Many studies have confirmed that acupuncture can effectively regulate astrocyte activity in ischemic stroke through these approaches: repairing astrocyte morphology structure, regu-lating energy metabolism, inhibiting excitotoxicity, inhibiting inflammation response and promoting nerve regeneration. In this paper, the authors summarized the relationship between astrocyte and ischemic stroke, and discussed the mechanisms of acupuncture therapy underlying improvement of ischemic stroke. Additionally, the authors also put forward some suggestions about future researches on acupuncture in ischemic stroke.


Assuntos
Terapia por Acupuntura , Isquemia Encefálica , Acidente Vascular Cerebral , Astrócitos , Isquemia Encefálica/terapia , Humanos , Regeneração Nervosa , Acidente Vascular Cerebral/terapia
11.
Bratisl Lek Listy ; 120(10): 777-782, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31663354

RESUMO

AIM: The aim of this study was to evaluate the efficacy of trimetazidine(TMZ) after end-to-end repair in a peripheral nerve injury model. METHOD: We performed end-to-end primary repair of sciatic nerves in rats and showed TMZ's regenerative effect. For this objective 30 male Sprague Dawley albino rats were used. Surgery+water group, rats were assigned to a placebo group and were given water by oral gavage. Surgery+TMZ group, rats were given trimetazidine by oral gavage. All medications were given for 12 weeks. Motor function test was performed. Afterwards, electromyography (EMG) recording was done. Finally, blood samples were taken, the animals were euthanized andsciatic nerve was removed. RESULTS: The amplitudes of compound muscle action potential (CMAP) increased significantly in the Surgery+TMZ group when compared with the group that have been given Surgery+Water. Nerve growth factor (NGF) immunoexpression in the Schwann cell was significantly increased in the Surgery+TMZ group compared with the Surgery+Water group. Moreover, fibrosis score was reduced in the Surgery+TMZ group compared to the Surgery+Water group.CONCLUSIONS: In conclusion, we demonstrated the superiority of TMZ on nerve healing in our experimental study which was evaluated with comparative groups (Tab. 3, Fig. 2, Ref. 31).


Assuntos
Regeneração Nervosa/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Nervo Isquiático/lesões , Trimetazidina/farmacologia , Animais , Masculino , Ratos , Ratos Sprague-Dawley
12.
Nat Neurosci ; 22(11): 1913-1924, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31591560

RESUMO

Axonal injury results in regenerative success or failure, depending on whether the axon lies in the peripheral or the CNS, respectively. The present study addresses whether epigenetic signatures in dorsal root ganglia discriminate between regenerative and non-regenerative axonal injury. Chromatin immunoprecipitation for the histone 3 (H3) post-translational modifications H3K9ac, H3K27ac and H3K27me3; an assay for transposase-accessible chromatin; and RNA sequencing were performed in dorsal root ganglia after sciatic nerve or dorsal column axotomy. Distinct histone acetylation and chromatin accessibility signatures correlated with gene expression after peripheral, but not central, axonal injury. DNA-footprinting analyses revealed new transcriptional regulators associated with regenerative ability. Machine-learning algorithms inferred the direction of most of the gene expression changes. Neuronal conditional deletion of the chromatin remodeler CCCTC-binding factor impaired nerve regeneration, implicating chromatin organization in the regenerative competence. Altogether, the present study offers the first epigenomic map providing insight into the transcriptional response to injury and the differential regenerative ability of sensory neurons.


Assuntos
Axônios/fisiologia , Epigenômica , Gânglios Espinais/fisiologia , Regeneração Nervosa/fisiologia , Células Receptoras Sensoriais/fisiologia , Acetilação , Algoritmos , Animais , Fator de Ligação a CCCTC/genética , Cromatina/metabolismo , Feminino , Gânglios Espinais/lesões , Expressão Gênica , Histonas/metabolismo , Aprendizado de Máquina , Masculino , Camundongos , Camundongos Transgênicos , Nervo Isquiático/lesões , Análise de Sequência de RNA
13.
Expert Rev Clin Pharmacol ; 12(11): 1047-1057, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31575290

RESUMO

Introduction: The clinical use of tacrolimus is characterized by many side effects which include neurotoxicity. In contrast, tacrolimus has also shown to have neuroregenerative properties. On a molecular level, the mechanisms of action could provide us more insight into understanding the neurobiological effects. The aim of this article is to review current evidence regarding the use of tacrolimus in peripheral nerve injuries.Areas covered: Available data on tacrolimus' indications were summarized and molecular mechanisms were elucidated to possibly understand the conflicting neurotoxic and neuroregenerative effects. The potential clinical applications of tacrolimus, as immunosuppressant and enhancer of nerve regeneration in peripheral nerve injuries, are discussed. Finally, concepts of delivery are explored.Expert opinion: It is unclear what the exact neurobiological effects of tacrolimus are. Besides its known calcineurin inhibiting properties, the mechanism of action of tacrolimus is mediated by its binding to FK506-binding protein-52, resulting in a bimodal dose response. Experimental models found that tacrolimus administration is preferred up to three days prior to or within 10 days post-nerve reconstruction. Moreover, the indication for the use of tacrolimus has been expanding to fields of dermatology, ophthalmology, orthopedic surgery and rheumatology to improve outcomes after various indications.


Assuntos
Regeneração Nervosa/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Tacrolimo/administração & dosagem , Animais , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/farmacologia , Esquema de Medicação , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/farmacologia , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/fisiopatologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Tacrolimo/efeitos adversos , Tacrolimo/farmacologia
14.
J Craniofac Surg ; 30(8): 2635-2639, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31577651

RESUMO

PURPOSE: This study was conducted to determine the effects of different doses and methods of extracorporeal shock wave treatment (ESWT) on the sciatic nerve regeneration of rat model using unbiased quantitative stereological techniques and to know which method and dose were effective. METHODS: Twenty-five Wistar albino rats were used in the experiment. All animals were randomly divided into 5 groups. To the first group (control, n = 5) ESWT and surgery were not applied. To 2nd group (E300*2, n = 5), twice doses of 300 impulses uESWs (unfocused) were applied. To 3rd group (E500*2, n = 5), twice doses of 500 impulses uESWs (unfocused) were applied. To 4th group (E300*2, n = 5), twice doses of 300 impulses of fESWs (focused) were applied. To 5th group (E500*2, n = 5), twice doses of 500 impulses of fESWs (focused) were applied. Rats were sacrificed and nerve samples analyzed on the 22nd day following the operation. RESULTS: There is a variable increase in the axon numbers among the shockwave treated groups in compare to the control group. The focused groups showed better improvement and the 300-focused group has shown the highest regeneration rate. CONCLUSION: The authors found that ESWT promotes nerve regeneration, increases the thickness of the myelin sheath and that the most effective result is in the 300 shock wave.


Assuntos
Regeneração Nervosa , Animais , Tratamento por Ondas de Choque Extracorpóreas , Ondas de Choque de Alta Energia , Masculino , Bainha de Mielina , Ratos , Ratos Wistar , Nervo Isquiático
15.
An Acad Bras Cienc ; 91(3): e20190068, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31508664

RESUMO

To investigate the mechanism of different exercise patterns on neurological function after focal cerebral ischaemia in rats. Rats with focal cerebral cerebral ischaemia were randomly divided into an aerobic exercise group, an exhaustive exercise group and a control group, with 8 rats in each group. A score for nerve function in each group was calculated, and the ultrastructure of nerve cells was observed. Levels of NO and NOS in the brain motor area of the ​​rats were measured in each group. The aerobic exercise group had lower nerve function scores than the exhaustive exercise group and higher scores than the control group (P<0.05). Under transmission electron microscopy, irregular shapes and organs were observed in nerve cells in the control group, while regular cell shapes and organs were observed in the aerobic exercise group. The aerobic exercise group and exhaustive exercise group had higher measures of NO content, NOS activity and eNOS, nNOS and iNOS gene expression than the control group, but eNOS expression in the aerobic exercise group and iNOS expression in the exhaustive exercise group were clearly higher according to RT-PCR (P<0.05). Aerobic exercise can promote the expression of NOS, mainly in eNOS, which can promote nerve repair.


Assuntos
Isquemia Encefálica/fisiopatologia , Regeneração Nervosa/fisiologia , Óxido Nítrico/fisiologia , Condicionamento Físico Animal/métodos , Animais , Isquemia Encefálica/terapia , Modelos Animais de Doenças , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos Sprague-Dawley
16.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(9): 1162-1168, 2019 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-31512460

RESUMO

Objective: To study the expressions of microRNA-221 (miR-221) and the protein of phosphatase and tension protein homologue (PTEN) in the proximal and distal stumps after sciatic nerve injury in rats and their correlation with the repair of peripheral nerve injury, so as to provide a new target for clinical diagnosis of peripheral nerve injury. Methods: Ninety-six male Sprague-Dawley rats of SPF grade were selected to establish sciatic nerve injury models. Twenty-four rats were sacrificed at 0 (immediately after operation), 1, 4, and 7 days after operation. The proximal and distal sciatic nerve fragments were taken under aseptic conditions. The expression of miR-221 was detected by real-time fluorescent quantitative PCR, and the expression of PTEN protein was detected by Western blot and immunofluorescent staining. The relationship between miR-221 and PTEN was verified by dual-luciferase reporter gene. At the same time, the ultrastructure of nerve stump was observed by transmission electron microscopy. Results: The results of real-time fluorescent quantitative PCR, Western blot, and immunofluorescence staining showed that the relative expression of miR-221 in the proximal and distal stumps increased gradually with time, and the relative expression of PTEN protein decreased gradually, and the differences between different time points after operation were significant ( P<0.05). At 1, 4, and 7 days after operation, the relative expression of miR-221 in proximal stump was significantly higher than that in distal stump, and the relative expression of PTEN protein in proximal stump was significantly lower than that in distal stump ( P<0.05). Dual-luciferase reporter gene suggested that PTEN was the target for miR-221. Transmission electron microscopy observation showed that the normal morphological structure was observed at 0 day after operation, and the proliferation of Schwann cells and degeneration of axons and myelin sheaths gradually increased with time. There was no significant difference between proximal and distal stumps at 1 day after operation. At 4 and 7 days, Schwann cells proliferated more in proximal stump than in distal stump, and the degeneration of axons and myelin sheaths was less. Conclusion: After sciatic nerve injury in rats, the up-regulation of the miR-221 expression targets the down-regulation of PTEN expression, which results in the difference of expression levels of miR-221 and PTEN in proximal and distal stumps. This phenomenon may play a role in promoting nerve repair after peripheral nerve injury.


Assuntos
Regulação da Expressão Gênica , MicroRNAs , PTEN Fosfo-Hidrolase , Traumatismos dos Nervos Periféricos , Nervo Isquiático , Animais , Axônios , Masculino , MicroRNAs/genética , Regeneração Nervosa/genética , PTEN Fosfo-Hidrolase/genética , Traumatismos dos Nervos Periféricos/fisiopatologia , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/fisiopatologia
17.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(4): 350-354, 2019 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-31512824

RESUMO

OBJECTIVE: To investigate the effect of platelet-derived growth factor (PDGF) on nerve regeneration in peri-implant tissues. METHODS: SD rats with implants in their femurs were injected with PDGF solution. The effects of PDGF on nerve regeneration in peri-implant tissues were analyzed by immunohistochemical staining. RESULTS: PDGF increased the number of nerve fibers in peri-implant tissues at early stage. PDGF had no significant effect on the number of nerve fibers in peri-implant tissues at late stage. Moreover, these nerves had a typical structure of peripheral nerve fibers. CONCLUSIONS: PDGF can promote nerve regeneration in peri-implant tissues at early stage. This study provided a certain experimental basis for the clinical application of PDGF to promote nerve regeneration and further improve the sensory function of the implant.


Assuntos
Implantes Dentários , Fator de Crescimento Derivado de Plaquetas , Animais , Fibras Nervosas , Regeneração Nervosa , Ratos , Ratos Sprague-Dawley
18.
Int J Nanomedicine ; 14: 5925-5942, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534331

RESUMO

Mesenchymal stem cells (MSCs) intrinsically possess unique features that not only help in their migration towards the tumor-rich environment but they also secrete versatile types of secretomes to induce nerve regeneration and analgesic effects at inflammatory sites. As a matter of course, engineering MSCs to enhance their intrinsic abilities is growing in interest in the oncology and regenerative field. However, the concern of possible tumorigenesis of genetically modified MSCs prompted the development of non-viral transfected MSCs armed with nanotechnology for more effective cancer and regenerative treatment. Despite the fact that a large number of successful studies have expanded our current knowledge in tumor-specific targeting, targeting damaged brain site remains enigmatic due to the presence of a blood-brain barrier (BBB). A BBB is a barrier that separates blood from brain, but MSCs with intrinsic features of transmigration across the BBB can efficiently deliver desired drugs to target sites. Importantly, MSCs, when mediated by nanoparticles, can further enhance tumor tropism and can regenerate the damaged neurons in the central nervous system through the promotion of axon growth. This review highlights the homing and nerve regenerative abilities of MSCs in order to provide a better understanding of potential cell therapeutic applications of non-genetically engineered MSCs with the aid of nanotechnology.


Assuntos
Neoplasias Encefálicas/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Nanotecnologia/métodos , Regeneração Nervosa , Animais , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/patologia , Humanos , Tropismo
19.
Eur Cytokine Netw ; 30(2): 59-66, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31486397

RESUMO

Recent studies have demonstrated that nicotine exhibited anti-inflammatory and neuroprotective properties by interacting with the alpha 7 nicotinic acetylcholine receptor (α7nAChR). However, the role of nicotine in regeneration during peripheral nerve injury has not been elucidated. The aim of this study was to investigate whether nicotine down-regulated production of proinflammatory cytokines and promoted peripheral nerve regeneration in rats. Rats challenged with sciatic nerve crush injury were treated with nicotine (1.5 mg/kg), three times per day. The expression of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin (IL-1ß), pinch test results, growth-associated protein 43 (GAP-43) expression, morphometric analyses, and the sciatic functional indexes were determined in sciatic nerves. Treatment with nicotine decreased local levels of TNF-α and IL-1ß, and increased the expression of GAP-43. Nicotine also improved nerve regeneration and functional recovery. The overall protective effects of nicotine were reversed by concomitant treatment with α7nACHR antagonist methyllycaconitine, indicating that nicotine exerted its specific anti-inflammatory and neuroprotective effects through the α7nAChR. These findings show that nicotine administration can provide a potential therapeutic pathway for the treatment of peripheral nerve injury, by a direct protective effect through the α7nAChR-mediated cholinergic anti-inflammatory pathway.


Assuntos
Lesões por Esmagamento/metabolismo , Lesões por Esmagamento/patologia , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Fármacos Neuroprotetores/farmacologia , Nicotina/farmacologia , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia , Animais , Modelos Animais de Doenças , Proteína GAP-43/metabolismo , Interleucina-1beta/metabolismo , Masculino , Atividade Motora/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Ratos Wistar , Nervo Isquiático/efeitos dos fármacos , Células Receptoras Sensoriais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
20.
Molecules ; 24(18)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487775

RESUMO

Neuroinflammatory microenvironment, regulating neurite regrowth and neuronal survival, plays a critical role in Alzheimer's disease (AD). During neuroinflammation, microglia are activated, inducing the release of inflammatory or anti-inflammatory factors depending on their polarization into classical M1 microglia or alternative M2 phenotype. Therefore, optimizing brain microenvironment by small molecule-targeted microglia polarization and promoting neurite regeneration might be a potential therapeutic strategy for AD. In this study, we found platycodigenin, a naturally occurring triterpenoid, promoted M2 polarization and inhibited M1 polarization in lipopolysaccharide (LPS)-stimulated BV2 and primary microglia. Platycodigenin downregulated pro-inflammatory molecules such as interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6 and nitric oxide (NO), while upregulated anti-inflammatory cytokine IL-10. Further investigation confirmed that platycodigenin inhibited cyclooxygenase-2 (Cox2) positive M1 but increased Ym1/2 positive M2 microglial polarization in primary microglia. In addition, platycodigenin significantly decreased LPS-induced the hyperphosphorylation of mitogen-activated protein kinase (MAPK) p38 and nuclear factor-κB (NF-κB) p65 subunits. Furthermore, the inactivation of peroxisome proliferators-activated receptor γ (PPARγ) induced by LPS was completely ameliorated by platycodigenin. Platycodigenin also promoted neurite regeneration and neuronal survival after Aß treatment in primary cortical neurons. Taken together, our study for the first time clarified that platycodigenin effectively ameliorated LPS-induced inflammation and Aß-induced neurite atrophy and neuronal death.


Assuntos
Microglia/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Neuritos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Saponinas/farmacologia , Plasticidade Celular/efeitos dos fármacos , Plasticidade Celular/imunologia , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Microglia/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Neuritos/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Óxido Nítrico/metabolismo , PPAR gama/metabolismo , Transdução de Sinais/efeitos dos fármacos
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