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Article in Chinese | WPRIM | ID: wpr-879412


Perineuronal nets (PNNs) is a complex network composed of highly condensed extracellular matrix molecules surrounding neurons. It plays an important role in maintaining the performance of neurons and protecting them from harmful substances. However, after spinal cord injury, PNNs forms a physical barrier that surrounds the neuron and limits neuroplasticity, impedes axonal regeneration and myelin formation, and promotes local neuroinflammatory uptake. This paper mainly describes the composition and function of PNNs of neurons and its regulatory effects on axonal regeneration, myelin formation and neuroinflammation after spinal cord injury.

Axons , Extracellular Matrix , Humans , Nerve Regeneration , Neuronal Plasticity , Neurons , Spinal Cord , Spinal Cord Injuries
Braz. j. med. biol. res ; 54(9): e10842, 2021. tab, graf
Article in English | LILACS | ID: biblio-1249339


Regeneration of injured peripheral nerves is an extremely complex process. Nogo-A (neurite outgrowth inhibitor-A) inhibits axonal regeneration by interacting with Nogo receptor in the myelin sheath of the central nervous system (CNS). The aim of this study was to investigate the effects of Nogo-A and its receptor on the repair of sciatic nerve injury in rats. Sprague-Dawley rats (n=96) were randomly divided into 4 groups: control group (control), sciatic nerve transection group (model), immediate repair group (immediate repair), and delayed repair group (delayed repair). The rats were euthanized 1 week and 6 weeks after operation. The injured end tissues of the spinal cord and sciatic nerve were obtained. The protein expressions of Nogo-A and Nogo-66 receptor (NgR) were detected by immunohistochemistry. The protein expressions of Nogo-A, NgR, and Ras homolog family member A (RhoA) were detected by western blot. At 1 week after operation, the pathological changes in the immediate repaired group were less, and the protein expressions of Nogo-A, NgR, and RhoA in the spinal cord and sciatic nerve tissues were decreased (P<0.05) compared with the model group. After 6 weeks, the pathological changes in the immediate repair group and the delayed repair group were alleviated and the protein expressions decreased (P<0.05). The situation of the immediate repair group was better than that of the delayed repair group. Our data suggest that the expression of Nogo-A and its receptor increased after sciatic nerve injury, indicating that Nogo-A and its receptor play an inhibitory role in the repair process of sciatic nerve injury in rats.

Animals , Rats , Receptors, Cell Surface , Myelin Proteins , Sciatic Nerve , Rats, Sprague-Dawley , GPI-Linked Proteins , Nogo Proteins , Nerve Regeneration
Braz. j. otorhinolaryngol. (Impr.) ; 86(5): 525-533, Sept.-Oct. 2020. tab, graf
Article in English | LILACS | ID: biblio-1132644


Abstract Introduction: Olfactory ensheathing cell is a unique kind of glia cells, which can promote axon growth. Little is known about the differences between olfactory mucosa olfactory ensheathing cells and olfactory bulb olfactory ensheathing cells in the capability to promote nerve regeneration. Objective: To study the recovery of the rat facial nerve after olfactory ensheathing cells transplantation, and to compare the differences between the facial nerve regeneration of olfactory mucosa-olfactory ensheathing cells and olfactory bulb olfactory bulb olfactory ensheathing cells transplantation. Methods: Institutional ethical guideline was followed (201510129A). Olfactory mucosa-olfactory ensheathing cells and olfactory bulb olfactory ensheathing cells were cultured and harvested after 7 days in vitro. 36 Sprague Dawley male rats were randomly divided into three different groups depending on the transplanting cells: Group A: olfactory mucosa-olfactory ensheathing cells; Group B: olfactory bulb olfactory ensheathing cells; Group C: DF-12 medium/fetal bovine serum. The main trunk of the facial nerve was transected and both stumps were inserted into a polylactic acid/chitosan conduit, then the transplanted cells were injected into the collagen in the conduits. After 4 and 8 weeks after the transplant, the rats of the three groups were scarified and the facial function score, facial nerve evoked potentials, histology analysis, and fluorescent retrograde tracing were tested and recorded, respectively, to evaluate the facial nerve regeneration and to analysis the differences among the three groups. Results: Olfactory ensheathing cells can promote the facial nerve regeneration. Compared with olfactory bulb olfactory ensheathing cells, olfactory mucosa olfactory ensheathing cells were more effective in promoting facial nerve regeneration, and this difference was more significant 8 weeks after the transplantation than 4 weeks. Conclusion: We discovered that olfactory ensheathing cells with nerve conduit could improve the facial nerve recovery, and the olfactory mucosa olfactory ensheathing cells are more effective for facial nerve regeneration compared with olfactory bulb olfactory ensheathing cells 8 weeks after the transplantation. These results could cast new light in the therapy of facial nerve defect, and furnish the foundation of auto-transplantation of olfactory mucosa olfactory ensheathing cells in periphery nerve injury.

Resumo Introdução: A célula embainhante olfatória é um tipo especial de célula glial que pode promover o crescimento do axônio. Pouco se sabe sobre as diferenças entre as células embainhantes olfatórias da mucosa olfatória e as células embainhantes olfatórias do bulbo olfatório em relação à sua capacidade de promover a regeneração nervosa. Objetivo: Estudar a regeneração do nervo facial de ratos após o transplante de células embainhantes olfatórias e comparar as diferenças entre a regeneração do nervo facial com o transplante de células embainhantes olfatórias da mucosa olfatória e de células embainhantes olfatórias do bulbo olfatório. Método: As recomendações éticas da instituição (201510129A) foram seguidas. Células embainhantes olfatórias da mucosa olfatória e células embainhantes olfatórias do bulbo olfatório foram cultivadas in vitro e coletadas após sete dias. Trinta e seis ratos Sprague Dawley machos foram divididos aleatoriamente em três grupos, dependeu das células transplantadas: Grupo A, células embainhantes olfatórias da mucosa olfatória; Grupo B, células embainhantes olfatórias do bulbo olfatório; Grupo C, meio de DF-12/soro fetal bovino. O tronco principal do nervo facial foi seccionado e ambos os cotos foram inseridos em um conduto de ácido polilático/quitosana; em seguida, as células transplantadas foram injetadas em colágeno nos condutos. Após quatro e oito semanas do transplante, os ratos dos três grupos foram agitados para a obtenção do escore da função facial, potenciais evocados do nervo facial, análise histológica e marcador fluorescente retrógrado, que foram testados e registrados, respectivamente, para avaliar a regeneração do nervo facial e analisar as diferenças entre os três grupos. Resultados: Células embainhantes olfatórias podem promover a regeneração do nervo facial. Em comparação com as células embainhantes olfatórias do bulbo olfatório, as células embainhantes olfatórias da mucosa olfatória foram mais eficazes na promoção da regeneração do nervo facial e essa diferença foi mais significativa oito semanas após o transplante em comparação com quatro semanas. Conclusão: Verificamos que células embainhantes olfatórias com conduto nervoso podem melhorar a recuperação do nervo facial e as células embainhantes olfatórias da mucosa olfatória são mais eficazes para a regeneração do nervo facial em comparação com as células embainhantes olfatórias do bulbo olfatório oito semanas após o transplante. Esses resultados podem lançar uma nova luz no tratamento de defeitos do nervo facial e fornecer a base do autotransplante de células embainhantes olfatórias da mucosa olfatória em lesões do nervo periférico.

Animals , Male , Rats , Facial Nerve , Nerve Regeneration , Olfactory Bulb , Olfactory Mucosa , Rats, Sprague-Dawley
ABCS health sci ; 45: e020016, 02 jun 2020. tab, ilus, graf
Article in English | LILACS | ID: biblio-1123701


INTRODUCTION: Different studies have evaluated the effects of electrophysical agents on regeneration after peripheral nerve injury. Among them, the most used in clinical and experimental research is photobiomodulation therapy (PBMT). OBJECTIVE: To analyze the effect of standard energy (16.8 J) of PBMT on peripheral nerve regeneration, applied at different periods after sciatic nerve injury in mice. METHODS: Thirty male Swiss mice were divided into six groups: naive; sham; control; LLLT-01 (660 nm, 16.8 J of total energy emitted in 1 day); LLLT-04 (660 nm, 4.2 J per day, 16.8 J of total energy emitted in 4 days); LLLT-28, (660 nm, 0.6 J per day, 16.8 J of total energy emitted over 28 days). The animals were evaluated using thermal hyperalgesia, Sciatic Functional Index (SFI), and Static Sciatic Index (SSI). Data were obtained at baseline and after 7, 14, 21, and 28 days after surgery. RESULTS: For the SFI and SSI, all groups showed significant differences compared to the control group, and the LLLT-04 group presented the best results among those receiving PBMT. In the assessment of thermal hyperalgesia, there was a significant difference in the 14th day of evaluation in the LLLT-04 group. CONCLUSION: The application of 16.8 J was useful in sciatic nerve regeneration with an improvement of hyperalgesia, with higher efficacy when applied in four days (4.2 J/day).

INTRODUÇÃO: Estudos avaliaram os efeitos de diferentes terapias aplicadas após lesão nervosa periférica, com o intuito de promover a regeneração local. Dentre elas, a mais utilizada em pesquisa clínica e experimental é a terapia de fotobiomodulação (TFBM). OBJETIVO: Analisar o efeito da fotobiomodulação (16,8 J) na regeneração nervosa periférica, aplicada em diferentes regimes após a lesão do nervo ciático em camundongos. MÉTODOS: Foram utilizados trinta camundongos machos (Swiss) divididos em: naive; sham; controle; LBI-01 (660 nm, 16,8 J de energia total emitida em 1 dia); LBI-04 (660 nm, 4,2 J por dia, 16,8 J de energia total emitida em 4 dias); LBI-28, (660 nm, 0,6 J por dia, 16,8 J de energia total emitida durante 28 dias). Os animais foram avaliados utilizando a hiperalgesia térmica, Índice Funcional do Ciático (IFC) e Índice estático do ciático (IEC). Os dados foram obtidos na linha de base e após 7, 14, 21, e 28 dias após a cirurgia. RESULTADOS: Para o IFC e IEC, todos os grupos mostraram um aumento no valor e diferenças significativas em relação ao grupo de controle, e o grupo LBI-04 apresentou os melhores resultados, alcançando valor basal no 21° dia dentre os que foram submetidos a TFBM. Na avaliação da hiperalgesia térmica, houve aumento do tempo de resposta com diferença significativa no 14° dia de avaliação no grupo LBI-04. CONCLUSÃO: A aplicação de 16,8 J foi eficaz na regeneração do nervo ciático quando distribuída ao longo dos 4 primeiros dias pós-lesão, com dose diária de 4,2 J/ponto.

Animals , Male , Mice , Sciatic Neuropathy/radiotherapy , Low-Level Light Therapy , Nerve Regeneration , Surgical Procedures, Operative , Crush Injuries , Hyperalgesia , Lasers
Rev. bras. ortop ; 55(3): 323-328, May-June 2020. tab, graf
Article in English | LILACS | ID: biblio-1138032


Abstract Objective To evaluate the effects of swimming on nerve regeneration after sciatic nerve injury in Wistar rats. Methods A total of 30 Wistar rats was divided into 3 groups: Sham + Nat group animals that were not submitted to graft surgery and were submitted to swimming (n = 10); Graft group: animals submitted to autologous sciatic nerve graft (n = 10); and Graft + Nat group: animals submitted to autologous sciatic nerve graft surgery and to swimming (n = 10). The results were analyzed on the software (GraphPad Software, San Diego, CA, USA). Results In the first evaluation, all sciatic functional index (SFI) values were similar (p = 0.609). Thirty days after the surgical procedure, we observed differences between all the comparisons: Sham + Nat (−34.64 ± 13.89) versus Graft (−145.9 ± 26.06); Sham + Nat versus Graft + Nat (−89.40 ± 7.501); Graft (−145.9 ± 26.06) versus Graft + Nat (−89.40 ± 7.501). In the measurements (60 and 90 days), there was no statistical difference between the Graft and Graft + Nat groups, with significantly lower values in relation to the control group (p < 0.001). The number of motor neurons presented differences in the comparisons between the Sham + Nat and Graft groups (647.1 ± 16.42 versus 563.4 ± 8.07; p < 0.05), and between the Sham + Nat and Graft + Nat groups (647.1 ± 16.42 versus 558.8 ± 14.79; p < 0.05). There was no difference between the Graft and Graft + Nat groups. Conclusion Animals submitted to the swimming protocol after the sciatic nerve grafting procedure did not present differences in the SFI values and motor neuron numbers when compared to the control group. Therefore, this type of protocol is not efficient for the rehabilitation of peripheral nerve lesions that require grafting. Therefore, further studies are needed.

Resumo Objetivo Avaliar os efeitos da natação na regeneração nervosa após a lesão do nervo ciático em ratos Wistar. Métodos Um total de 30 ratos Wistar foram divididos em 3 grupos: grupo Sham + Nat: animais que não foram submetidos à cirurgia de enxerto e foram submetidos à natação (n = 10); grupo Enxerto: animais que foram submetidos à cirurgia de enxerto autólogo de nervo ciático (n = 10); e grupo Enx + Nat: animais submetidos à cirurgia de enxerto autólogo de nervo ciático e à natação (n = 10). Os resultados foram analisados pelo software GraphPad Prism 5.0 (GraphPad Software, San Diego, CA, EUA). Resultados Na primeira avaliação, todos os valores do índice funcional do ciático (IFC) foram semelhantes (p = 0.609). Após 30 dias do procedimento cirúrgico, foram observadas diferenças entre todas as comparações: Sham + Nat (−34,64 ± 13,89) versus Enxerto (−145,9 ± 26,06), grupos Sham + Nat versus Enx + Nat (−89,40 ± 7,501), grupos Enxerto (−145,9 ± 26,06) versus Enx + Nat (−89,40 ± 7,501). Nas medidas (60 e 90 dias), não houve diferença estatística entre os grupos Enxerto e Enx + Nat, com valores significativamente menores em relação ao grupo controle (p < 0,001). O número de motoneurônios apresentou diferenças nas comparações entre os grupos Sham + Nat e Enxerto (647,1 ± 16,42 versus 563,4 ± 8,07; p < 0,05) e Sham + Nat e Enx + Nat (647,1 ± 16,42 versus 558,8 ± 14,79; p < 0,05), não havendo diferença entre os grupos Enxerto e Enx + Nat. Conclusão Os animais submetidos ao protocolo de natação após o procedimento de enxerto do nervo ciático não apresentaram diferenças nos valores de IFC e nos números de motoneurônios quando comparados com grupo controle. Portanto, este tipo de protocolo não é eficiente para reabilitação de lesões nervosas periféricas que necessitam de enxerto, sendo necessários novos estudos.

Animals , Rats , Rehabilitation , Sciatic Nerve , Surgical Procedures, Operative , Swimming , Rats, Wistar , Peripheral Nerve Injuries , Nerve Regeneration
Article in Chinese | WPRIM | ID: wpr-781344


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.

Animals , Facial Nerve , Facial Paralysis , Nerve Regeneration , Stem Cells , Vibrissae
Article in Chinese | WPRIM | ID: wpr-828540


The intrinsic regrowth ability of injured neurons is essential for axon regeneration and functional recovery. Recently, numerous intrinsic pathways that regulate axon regeneration have been discovered, among which the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway are arguably the best characterized examples. MAPK signaling pathway is involved in multiple processes including sensing injury signals, initiating and promoting axonal regrowth through regulating cytoskeleton dynamics and protein synthesis. The PI3K/Akt signaling pathway regulates axon regeneration mainly through gene transcription and translation. Combinatory manipulation of multiple regeneration-promoting signals can further improve the extend of axonal regrowth. This paper summarizes current progresses on axon regeneration studies in various organisms and discuss their potentials in promoting functional recovery .

Axons , Physiology , Nerve Regeneration , Neurons , Phosphatidylinositol 3-Kinases , Regeneration , Signal Transduction
Arch. endocrinol. metab. (Online) ; 63(6): 549-556, Nov.-Dec. 2019. graf
Article in English | LILACS | ID: biblio-1055020


ABSTRACT Growth hormone (GH) is best known for its effect stimulating tissue and somatic growth through the regulation of cell division, regeneration and proliferation. However, GH-responsive neurons are spread over the entire central nervous system, suggesting that they have important roles in the brain. The objective of the present review is to summarize and discuss the potential physiological importance of GH action in the central nervous system. We provide evidence that GH signaling in the brain regulates the physiology of numerous functions such as cognition, behavior, neuroendocrine changes and metabolism. Data obtained from experimental animal models have shown that disruptions in GH signaling in specific neuronal populations can affect the reproductive axis and impair food intake during glucoprivic conditions, neuroendocrine adaptions during food restriction, and counter-regulatory responses to hypoglycemia, and they can modify gestational metabolic adaptions. Therefore, the brain is an important target tissue of GH, and changes in GH action in the central nervous system can explain some dysfunctions presented by individuals with excessive or deficient GH secretion. Furthermore, GH acts in specific neuronal populations during situations of metabolic stress to promote appropriate physiological adjustments that restore homeostasis. Arch Endocrinol Metab. 2019;63(6):549-56

Humans , Brain/metabolism , Neuroprotective Agents/metabolism , Human Growth Hormone/metabolism , Metabolic Networks and Pathways/physiology , Signal Transduction , Nerve Regeneration/physiology
Fisioter. Pesqui. (Online) ; 26(3): 220-226, jul.-set. 2019. graf
Article in Portuguese | LILACS | ID: biblio-1039896


RESUMO Lesões de nervos periféricos levam a perda funcional elevada no tecido muscular. Assim, muitas pesquisas têm investigado técnicas cirúrgicas, como neurorrafias, e recursos terapêuticos, como eletroestimulação, para melhorar a funcionalidade de um músculo reinervado após lesão periférica. Este estudo tem como objetivo investigar os efeitos da eletroestimulação com corrente russa (2.500Hz, 4ms, 10 seg. de contração por 20 seg. de relaxamento, modulação de 10Hz e 100 Hz) na recuperação funcional após secção e neurorrafia término-lateral do coto distal do nervo fibular comum à face lateral do nervo tibial em ratos. Foram utilizados 25 ratos Wistar, machos, com 80 dias de vida, fornecidos pelo Biotério Central da Universidade Sagrado Coração (Bauru, SP, Brasil). Os animais foram divididos aleatoriamente em cinco grupos: grupo-controle Inicial (GCI), grupo-controle final (GCF), grupo experimental não tratado (GENT), grupo neurorrafia término-lateral com estimulação russa (GNTLER) e grupo-controle desnervado (GCD). A corrente russa foi iniciada cinco dias após neurorrafia e aplicada no músculo tibial cranial do GNTLER, 3 vezes por semana, totalizando 36 sessões. A estimulação elétrica foi eficaz para aumentar a amplitude e diminuir a latência do músculo reinervado, além de aumentar a força muscular em comparação ao GCD. Diante disso, conclui-se que a eletroestimulação de média frequência (corrente russa) foi eficiente na recuperação funcional do músculo tibial cranial após neurorrafia término-lateral do nervo fibular comum.

RESUMEN Las lesiones de los nervios periféricos ocasionan una elevada pérdida funcional en el tejido muscular. De esta manera, en muchos estudios se han investigado técnicas quirúrgicas, como neurorrafias, y recursos terapéuticos, como la electroestimulación, para mejorar la funcionalidad del músculo reinervado tras una lesión periférica. El presente estudio tiene como objetivo investigar los efectos de la electroestimulación con corrente rusa (2.500Hz, 4ms, 10 seg. de contracción por 20 seg. de relajación, modulación de 10Hz y 100Hz) en la recuperación funcional tras la sección y neurorrafia término-lateral del muñón distal del nervio fibular común en la parte lateral del nervio tibial en ratas. Se utilizaron 25 ratas Wistar, machos, con 80 días de vida, proporcionadas por el Biotério Central de la Universidade do Sagrado Coração (Bauru, SP, Brasil). Se dividieron aleatoriamente los animales en cinco grupos: grupo de control inicial (GCI), grupo de control final (GCF), grupo experimental no tratado (GENT), grupo de neurorrafia término-lateral con estimulación rusa (GNTLER) y grupo de control denervado (GCD). La corriente rusa se inició cinco días tras la neurorrafia, siendo que la aplicó al músculo tibial craneal del GNTLER 3 veces a la semana, con un total de 36 sesiones. La estimulación eléctrica se mostró efectiva para aumentar la amplitud y disminuir la latencia del músculo reinervado, además de aumentar la fuerza muscular en comparación con el GCD. Por lo tanto, se concluye que la estimulación eléctrica de frecuencia media (corriente rusa) fue eficaz en la recuperación funcional del músculo tibial craneal tras la neurorrafia término-lateral del nervio fibular común.

ABSTRACT Peripheral nerve injury leads to a high functional loss of muscle tissue. Thus, many studies have investigated surgical techniques, such as neurorraphies, and therapeutic resources, such as electrical stimulation, to improve the functionality of reinnervated muscle after peripheral injury. This study aims to investigate the effects of electrical stimulation with Russian Current (2,500Hz, 4ms, 10:20 sec contraction/relaxation, modulated at 10Hz and 100Hz) in the functional recovery after section and end-to-side neurorrhaphy of the peroneal nerve distal stump common to the lateral face of the tibial nerve in rats. In this study, 25 male Wistar rats with 80 days of life were used, provided by the Universidade Sagrado Coração (USC), Bauru, SP, Brazil. The animals were randomly divided into five groups: Initial Control Group (ICG), Final Control Group (FCG), Untreated Experimental Group (UEG), End-to-Side Neurorrhaphy with Russian Stimulation Group (ENRSG), and Denervated Control Group (DCG). The Russian Current was started 5 days after neurorrhaphy and applied to the cranial tibial muscle of the ENRSG, 3 times a week, totaling 36 sessions. We observed that the electrical stimulation with Russian Current (ENRSG) was effective to increase amplitude (mV) and to decrease the latency (ms) of the reinnervated muscle, besides increasing the muscle strength when compared with the denervated control group. Therefore, we concluded that the average frequency electrical stimulation (Russian current) was efficient in the functional recovery of the cranial tibial muscle after the end-lateral neurorrhaphy of the common fibular nerve.

Animals , Male , Peroneal Nerve/physiology , Transcutaneous Electric Nerve Stimulation/methods , Nerve Regeneration , Rats, Wistar , Electromyography , Muscle Strength , Peripheral Nerve Injuries/surgery
Acta Physiologica Sinica ; (6): 454-462, 2019.
Article in Chinese | WPRIM | ID: wpr-777168


Neural stem cell therapy, as a new therapeutic method for neural diseases, has aroused a wide concern for over 20 years since neural stem cells were first found in 1992. Ischemic stroke is highly concerned because of its high incidence, mortality and disability rates. Because the brain has a limited ability to repair itself, to improve neural function and promote neural regeneration may help to prevent occurrence and development of neurological diseases. It is noteworthy that some stroke patients showed an ability to repair brain several months after the stroke happened, suggesting an existence of endogenous nerve repair in these patients. The research advances in functions of endogenous neural stem cells in neural regeneration and the related regulators after ischemic stroke are summarized in this review to provide new views of the mechanism of neural functional recovery after ischemic stroke.

Brain Ischemia , Therapeutics , Humans , Nerve Regeneration , Neural Stem Cells , Cell Biology , Stroke , Therapeutics
Article in Chinese | WPRIM | ID: wpr-772648


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.

Animals , Dental Implants , Nerve Fibers , Nerve Regeneration , Platelet-Derived Growth Factor , Rats , Rats, Sprague-Dawley
Frontiers of Medicine ; (4): 131-137, 2019.
Article in English | WPRIM | ID: wpr-771286


The inhibitory environment that surrounds the lesion site and the lack of intrinsic regenerative capacity of the adult mammalian central nervous system (CNS) impede the regrowth of injured axons and thereby the reestablishment of neural circuits required for functional recovery after spinal cord injuries (SCI). To circumvent these barriers, biomaterial scaffolds are applied to bridge the lesion gaps for the regrowing axons to follow, and, often by combining stem cell transplantation, to enable the local environment in the growth-supportive direction. Manipulations, such as the modulation of PTEN/mTOR pathways, can also enhance intrinsic CNS axon regrowth after injury. Given the complex pathophysiology of SCI, combining biomaterial scaffolds and genetic manipulation may provide synergistic effects and promote maximal axonal regrowth. Future directions will primarily focus on the translatability of these approaches and promote therapeutic avenues toward the functional rehabilitation of patients with SCIs.

Animals , Axons , Physiology , Biocompatible Materials , Genetic Enhancement , Methods , Humans , Nerve Regeneration , PTEN Phosphohydrolase , Metabolism , Recovery of Function , Spinal Cord Injuries , Tissue Engineering , Methods , Tissue Scaffolds
Int. j. morphol ; 37(1): 289-295, 2019. graf
Article in English | LILACS | ID: biblio-990040


SUMMARY: Peripheral nerve regeneration is a serious clinical problem. The goal of this work was to evaluate comparatively a biopolymer tube of sugarcane with an expanded polyethylene tube as a tube guide in peripheral nerve regeneration. Fourteen male albino Wistar rats were used, separated into three different groups: control (CG), lesion + polyethylene tube (PG) and lesion + sugarcane biopolymer (SBG). At 60 days old, animals from the PG and SBG underwent surgery for tubulization of the sciatic nerve, and 60 days after the injury they were sacrificed for collection of the nerve. In the analysis of the number of nerve fibers, a smaller number was seen in the PG and SBG groups compared to the CG, no difference was seen between the PG and SBG groups (p<0.05). With regard to the number of blood vessels, the SBG group had a larger number than the CG and PG groups (p<0.05). The SBG also presented increase on axonal diameter and G -ratio compared to PG (p<0.05). Taken together these data revealed that biopolymer tube favors a suitable environment for peripheral nerve regeneration.

RESUMEN: La regeneración nerviosa periférica es un problema clínico grave. El objetivo de este trabajo fue evaluar comparativamente un tubo de biopolímero de caña de azúcar con un tubo de polietileno expandido, como guía de tubo en la regeneración de nervios periféricos. Se utilizaron dieciocho ratas Wistar albinas macho, separadas en tres grupos: control (CG), lesión + tubo de polietileno (PG) y lesión + biopolímero de caña de azúcar (SBG). A los 60 días de edad, los animales del PG y SBG fueron sometidos a una cirugía para la tubulización del nervio ciático, y 60 días después de la lesión fueron sacrificados para la recolección del nervio. En el análisis del número de fibras nerviosas, se observó un número menor en los grupos PG y SBG en comparación con el CG; no se observaron diferencias entre los grupos PG y SBG (p <0,05). Con respecto al número de vasos sanguíneos, el grupo SBG tuvo un número mayor que los grupos CG y PG (p <0,05). El SBG también presentó un aumento en el diámetro axonal y la proporción G en comparación con PG (p <0,05). En conjunto, estos datos revelaron que el tubo de biopolímero favorece un entorno adecuado para la regeneración de nervios periféricos.

Animals , Rats , Sciatic Nerve/anatomy & histology , Biopolymers/chemistry , Saccharum/chemistry , Guided Tissue Regeneration/methods , Nerve Regeneration , Peripheral Nerves , Sciatic Nerve/surgery , Sciatic Nerve/physiology , Biocompatible Materials , Rats, Wistar
Int. j. morphol ; 37(1): 349-357, 2019. graf
Article in English | LILACS | ID: biblio-990050


SUMMARY: The aim of this study was to determine the possible regenerative effect of neuroectodermal stem cells on the ultrastructural, and locomotor function resulting from compressed injury to the spinal cord in a rat model. Forty male rats were divided into control and sham groups (20 rats each). Compressed spinal cord injured (CSCI) were forty rats which subdivided equally into: untreated, treated by neuroectodermal stem cells (NESCs). After four weeks, all rats in different groups were scarified, samples were taken from central, cranial, and caudal to the site of spinal cord injury. Specimens were prepared for light and electron microscopic examination. The number of remyelinated axons in central, cranial and caudal regions to the injured spinal cord after transplantation of NESCs was counted. The open field test assessed the locomotor function. Results revealed that compressed spinal cord injury resulted in loss and degeneration of numerous nerve fibers, myelin splitting and degeneration of mitochondria. Four weeks after transplantation of NESCs regenerated axons were noticed in cranial and central sites, while degenerate axons were noticed caudal to the lesion. Number of remyelinated axons was significantly increased in both central and cranial to the site of spinal cord injury in comparison with caudal region which had the least number of remyelinated axons. Transplantation of NESCs improved significantly the locomotor functional activity In conclusion, neuroectodermal stem cells transplantation ameliorated the histopathological and ultrastructural changes, and improved the functional locomotor activity in CSCI rat.

RESUMEN: El objetivo de este estudio fue determinar el posible efecto regenerativo de las células madre neuroectodérmicas en la función ultraestructural y locomotora de una lesión comprimida en la médula espinal en un modelo de rata. Cuarenta ratas macho se dividieron en grupos control y sham (20 ratas en cada grupo). La médula espinal lesionada (CSCI) tenía cuarenta ratas que se subdividieron de igual forma en los siguientes grupos: no tratadas, tratadas con células madre neuroectodérmicas (NESCs). Al término de cuatro semanas, todas las ratas en los diferentes grupos fueron escarificadas, se tomaron muestras de las áreas central, craneal y caudal en relación al sitio de la lesión de la médula espinal. Las muestras fueron preparadas para examen microscópico de luz y electrónica. Se contó el número de axones remielinizados en las regiones central, craneal y caudal de la médula espinal lesionada después del trasplante de NESCs. La prueba de campo abierto evaluó la función locomotora. Los resultados revelaron que la lesión de la médula espinal comprimida provocó la pérdida y degeneración de numerosas fibras nerviosas, la división de la mielina y la degeneración de las mitocondrias. Cuatro semanas después del trasplante de NESCs, se notaron axones regenerados en los sitios craneales y centrales, mientras que los axones degenerados se notaron caudal a la lesión. El número de axones remielinizados aumentó significativamente tanto en el centro como en el cráneo hasta el sitio de la lesión de la médula espinal en comparación con la región caudal que tenía el menor número de axones remielinizados. El trasplante de NESCs mejoró significativamente la actividad funcional locomotora. En conclusión, el trasplante de células madre neuroectodérmicas mejoró los cambios histopatológicos y ultraestructurales, y mejoró la actividad locomotora funcional en la rata CSCI.

Animals , Female , Rats , Spinal Cord Injuries/therapy , Stem Cell Transplantation/methods , Nerve Regeneration/physiology , Spinal Cord/ultrastructure , Axons , Motor Activity
Braz. j. med. biol. res ; 52(2): e7988, 2019. tab, graf
Article in English | LILACS | ID: biblio-984025


Recovery of motor function after central nervous system (CNS) injury is dependent on the regeneration capacity of the nervous system, which is a multifactorial process influenced, among other things, by the role of neuromodulators such as serotonin. The neurotransmitter serotonin can promote neuronal regeneration but there are also reports of it causing restriction, so it is important to clarify these divergent findings in order to understand the direct scope and side effects of potential pharmacological treatments. We evaluated the effect of serotonin on the extent of neuritic outgrowth and morphology of three different neuronal types in the leech Haementeria officinalis during their regeneration in vitro: Retzius interneurons (Rz), annulus erector (AE) motoneurons, and anterolateral number 1 (AL1) CNS neurons. Neurons were isolated and cultured in L15 medium, with or without serotonin. Growth parameters were registered and quantified, and observed differences were analyzed. The addition of serotonin was found to induce AL1 neurons to increase their average growth dramatically by 8.3-fold (P=0.02; n=5), and to have no clear effect on AE motoneurons (P=0.44; n=5). For Rz interneurons, which normally do not regenerate their neurites, the addition of concanavaline-A causes substantial growth, which serotonin was found to inhibit on average by 98% (P=0.02; n=5). The number of primary neurites and their branches were also affected. These results reveal that depending on the neuronal type, serotonin can promote, inhibit, or have no effect on neuronal regeneration. This suggests that after CNS injury, non-specific pharmacological treatments affecting serotonin may have different effects on different neuronal populations.

Animals , Serotonin/pharmacology , Central Nervous System/cytology , Neurites/drug effects , Leeches/drug effects , Motor Neurons/drug effects , Nerve Regeneration/drug effects , Concanavalin A/pharmacology , Neuronal Plasticity/drug effects
Acta cir. bras ; 33(10): 935-944, Oct. 2018. tab, graf
Article in English | LILACS | ID: biblio-973465


Abstract Purpose: To investigate the impact of bone mesenchymal stem cells (BMSCs) intervention on the viscoelasticity of sciatic nerve in rats with chronic alcohol intoxication (CAI). Methods: The CAI rat models were prepared, divided into model groups, and treated with either BMSCs or basic fibroblast growth factor (bFGF). Then the rats underwent electrophysiological test and the serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), and metallothionein (MT) were measured. Histological observation, stress relaxation test, and creep test were performed for the sciatic nerve of the CAI model in each group. Results: The MDA level of group BMSC was significantly lower (p<0.05) than that of groups MOD (the CIA model) and bFGF. The SOD and MT levels were higher in group BMSC than in groups MOD and bFGF (p<0.05). The motor nerve conduction velocity and amplitude were higher in group BMSC than in groups MOD and bFGF (p<0.05). The amounts of 7200s stress reduction and 7200 s strain increase of the sciatic nerve in group BMSC were greater than those in groups bFGF and MOD (p<0.05). Conclusion: Bone mesenchymal stem cells can improve the metabolism of free radicals, restore the tissue morphology and viscoelasticity of the chronic alcohol intoxication animal model, and positively affect the repairing of the injured sciatic nerve.

Animals , Male , Rats , Sciatic Nerve/physiopathology , Bone Marrow Transplantation , Mesenchymal Stem Cell Transplantation , Alcoholic Intoxication/physiopathology , Nerve Regeneration , Sciatic Nerve/pathology , Stress, Physiological , Superoxide Dismutase/blood , Viscosity , Bone Marrow Cells , Fibroblast Growth Factor 2 , Rats, Wistar , Disease Models, Animal , Alcoholic Intoxication/blood , Elasticity , Malondialdehyde/blood , Metallothionein/blood
Rev. bras. ortop ; 53(3): 276-280, May-June 2018. tab, graf
Article in English | LILACS | ID: biblio-959146


ABSTRACT Objective: To evaluate the neurotrophin mRNA expression and axon count in the median nerve of Wistar rats submitted to neural mobilization (NM) after nerve compression. Methods: Eighteen animals were randomly divided into G1 (nerve compression only), G2 (NM for 1 min), and G3 (NM for 3 min). For NM, the animals were anesthetized and the right scapula received the mobilization, adapted as indicated for humans, on alternate days, from the third to the 13th postoperative (PO) day, totaling six days of therapy. On the 14th PO day, animals were anesthetized and euthanized. Fragments of the median nerve, distal to the compression procedure, were removed for histomorphometric analysis and expression of neurotrophins, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) by RT-PCR. Results: Histomorphometric analysis revealed differences in the number of axons in the injured side, which was significantly lower in the injured limb nerve compared to the control limb, whereas the RT-PCR analysis showed no significant differences in the expression of NGF or BDNF. Conclusion: NM treatment did not affect median nerve regeneration, which maintained normal recovery rates.

RESUMO Objetivo: Avaliar a expressão de RNAm de neurotrofinas e a contagem de axônios no nervo mediano de ratos Wistar submetidos à mobilização neural (MN) após compressão nervosa. Métodos: Foram divididos aleatoriamente 18 animais em G1 (apenas compressão nervosa), G2 (MN por 1 minuto) e G3 (MN por 3 minutos). Para a MN, os animais foram anestesiados e o membro escapular direito recebeu a mobilização, adaptada da forma indicada para humanos, em dias alternados, do terceiro ao 13° dia de pós-operatório (PO), em seis dias de terapia. No 14° dia PO, os animais foram anestesiados e eutanasiados. Fragmentos do nervo mediano, distais ao procedimento de compressão, foram retirados para análise histomorfométrica e de expressão das neutrotrofinas, fator de crescimento do nervo (NGF) e fator de crescimento derivado do cérebro (BNDF) por RT-PCR. Resultados: A análise histomorfométrica evidenciou diferenças no número de axônios nos lados lesionados, que foi significativamente menor no nervo do membro lesado comparado com o membro controle; por sua vez, a análise por RT-PCR não apontou diferenças significativas na expressão de NGF e nem de BNDF. Conclusão: O tratamento de MN não afetou a regeneração do nervo mediano, que manteve índices normais de recuperação.

Animals , Rats , Exercise , Rats, Wistar , Intercellular Signaling Peptides and Proteins , Histology , Median Nerve , Nerve Regeneration
Article in English | WPRIM | ID: wpr-691404


<p><b>OBJECTIVE</b>To observe the effect of acupuncture on the Notch signaling pathway in rats with traumatic brain injury and to explore the pathogenesis of acupuncture intervention on traumatic brain injury.</p><p><b>METHODS</b>Feeney's freefall epidural impact method was used to establish a traumatic brain injury model in rats; the rats were randomly divided into a normal group, sham operation group, model group and acupuncture group. Acupuncture was performed in the Baihui (DU 20), Shuigou (DU 26), Fengfu (DU 16), Yamen (DU 15) and Hegu (LI 4) acupoints in the rat, and Yamen was punctured via Fengfu. Then, the rats in each group were randomly divided into three subgroups, namely the day 3 subgroup, day 7 subgroup and day 14 subgroup according to treatment duration. The modified neurological severity scores (mNss) method was used to perform neurobehavioral scoring for evaluating the degree of injury in the rats. The hematoxylin-eosin (HE) staining method was used to observe the pathological change in the brain tissue of rats in each group. Real-time fluorescent quantitative polymerase chain reaction (Q-PCR) technology was used to detect changes in the Notch1, Hes1 and Hes5 gene expression levels in the cortex on the injured side. Western blot was used to detect the protein expression changes.</p><p><b>RESULTS</b>One day after modeling, the mNss scores in the model group and in the acupuncture group were significantly higher than those in the normal and sham operation groups (P<0.01) ; there was no statistically significant difference between the normal group and the sham operation group. The scores decreased with increased treatment time, and the scores in the acupuncture group decreased more significantly than those in the model group (P<0.01). The pathological examination by the HE staining method demonstrated that the brain tissue of the rats in the acupuncture and model groups relatively significantly changed. The Notch1 gene expression level in the acupuncture group was significantly higher than the level in all of the other groups (P<0.01) ; the Hes1 and Hes5 gene expression levels were also higher in the acupuncture group. The expression changes of the Notch1 and Hes1 protein were consistent with that of mRNA. In each experimental group, the mNss score and the pathological results by the HE staining method were consistent with the mRNA results.</p><p><b>CONCLUSION</b>Acupuncture could significantly promote high expression levels of Notch1, Hes1 and Hes5 in the brain tissue of traumatic brain injury rats. Therefore, acupuncture might be an important intervention for inducing endogenous stem cell proliferation and for promoting nerve repair.</p>

Acupuncture Points , Acupuncture Therapy , Animals , Brain Injuries , Genetics , Pathology , Therapeutics , Brain Ischemia , Pathology , Therapeutics , Male , Nerve Regeneration , Genetics , Rats , Rats, Sprague-Dawley , Receptors, Notch , Genetics , Metabolism , Reperfusion Injury , Genetics , Therapeutics , Signal Transduction , Genetics
Article in English | WPRIM | ID: wpr-690640


<p><b>OBJECTIVE</b>To investigate the optimal timing for the repair of persistent incomplete facial paralysis by hypoglossal-facial 'side'-to-side neurorrhaphy in rats.</p><p><b>METHODS</b>A total of 30 adult rats with crushed and bulldog-clamped facial nerve injury were randomly divided into 5 groups (n = 6 each) that were subjected to injury without nerve repair or with immediate repair, 2-week-delayed repair, 4-week-delayed repair, or 8-week-delayed repair. Three months later, the effects of repair in each rat were evaluated by facial symmetry assessment, electrophysiological examination, retrograde labeling, and axon regeneration measurement.</p><p><b>RESULTS</b>At 3 months after injury, the alpha angle significantly increased in the group of rats with 4-week-delayed repair compared with the other four groups. Upon stimulation of the facial nerve or Pre degenerated nerve, the muscle action potentials MAPs were recorded in the whisker pad muscle, and the MAP amplitude and area under the curve in the 4-week-delayed repair group were significantly augmented at 3 months post-injury. Similarly, the number of retrograde-labeled motor neurons in the facial and hypoglossal nuclei was quantified to be significantly greater in the 4-week-delayed repair group than in the other groups, and a large number of regenerated axons was also observed.</p><p><b>CONCLUSION</b>The results of this study demonstrated that hemiHN-FN neurorrhaphy performed 4 weeks after facial nerve injury was most effective in terms of the functional recovery of axonal regeneration and activation of facial muscles.</p>

Animals , Disease Models, Animal , Facial Nerve , General Surgery , Facial Nerve Injuries , General Surgery , Facial Paralysis , General Surgery , Hypoglossal Nerve , General Surgery , Nerve Regeneration , Neurosurgical Procedures , Methods , Rats, Sprague-Dawley , Treatment Outcome
Article in English | WPRIM | ID: wpr-716160


BACKGROUND: The interplay between neurogenesis and angiogenesis is crucial during the development mediated by neuro-angiogenic morphogens. In particular, the angiogenic activity of neuropeptides and their role in tissue regeneration have long been investigated for better understanding of their biological mechanisms and further applications. However, there have been few studies for direct comparison of angiogenic activities of neuropeptides for in vitro and in vivo models. In this study, we report that direct comparison of the angiogenic activities of neuropeptide Y, secretoneurin, and substance P (SP) immobilized on hydrogels in in vitro and in vivo experiments. METHODS: A hyaluronic acid-based hydrogel is prepared by utilizing acrylated hyaluronic acid and thiolated peptides as a crosslinker and angiogenic factors, respectively. Angiogenic activities of three neuropeptides are evaluated not only by in vitro angiogenic and gene expression assays, but also by an in vivo chronic myocardial infarction model. RESULTS: The comparison of in vitro angiogenic activities of three peptides demonstrates that the SP-immobilized hydrogel shows a higher degree of cell network formation and angiogenic-specific genes than those of the other peptides and the control case. In addition, a three-dimensional angiogenic assay illustrates that more sprouting is observable in the SP group. Evaluation of regenerative activity in the chronic myocardial infarction model reveals that all three peptideimmobilized hydrogels induce increased cardiac function as well as structural regeneration. Among all the cases, the SP group provided the highest regenerative activity both in vitro and in vivo. CONCLUSION: In our comparison study, the SP-immobilized hydrogel shows the highest angiogenic activity and tissue regeneration among the test groups. This result suggests that nerve regeneration factors help angiogenesis in damaged tissues, which also highlights the importance of the neuro-angiogenic peptides as an element of tissue regeneration.

Angiogenesis Inducing Agents , Gene Expression , Hyaluronic Acid , Hydrogels , Hydrogels , In Vitro Techniques , Myocardial Infarction , Nerve Regeneration , Neurogenesis , Neuropeptide Y , Neuropeptides , Peptides , Regeneration , Substance P