Effect of Long-term Peripheral Nerve Stimulation on Neuro-Muscular Complex Morphologic Recovery in Experiment / Efecto de la Estimulación del Nervio Periférico a Largo Plazo sobre la Recuperación Morfológica del Complejo Neuromuscular en Experimento

SUMMARY: Peripheral nerve injury is an extremely important medical and socio-economic problem. It is far from a solution, despite on rapid development of technologies. To study the effect of long-term electrical stimulation of peripheral nerves, we used a domestically produced electrical stimulation system, which is approved for clinical use. The study was performed on 28 rabbits. Control of regeneration was carried out after 3 month with morphologic techniques. The use of long-term electrostimulation technology leads to an improvement in the results of the recovery of the nerve trunk after an injury, both directly at the site of damage, when stimulation begins in the early period, and indirectly, after the nerve fibers reach the effector muscle.

La lesión de los nervios periféricos es un problema médico y socioeconómico extremadamente importante. Sin embargo, y a pesar del rápido desarrollo de las tecnologías, aún no tiene solución. Para estudiar el efecto de la estimulación eléctrica a largo plazo de los nervios periféricos, utilizamos un sistema de estimulación eléctrica de producción nacional, que está aprobado para uso clínico. El estudio se realizó en 28 conejos. El control de la regeneración se realizó a los 3 meses con técnicas morfológicas. El uso de tecnología de electro estimulación a largo plazo conduce a una mejora en los resultados de la recuperación del tronco nervioso después de una lesión, tanto directamente en el lugar del daño, cuando la estimulación comienza en el período temprano, como indirectamente, después de que las fibras nerviosas alcanzan el músculo efector.

Investigation of the Neuro-Regenerative Effects of Bioresonance and Magnetotherapy in Sciatic Nerve Damage-Induced Rats / Investigación de los Efectos Neurorregenerativos de Biorresonancia y Magnetoterapia en Ratas Inducidas por Daño del Nervio Ciático

SUMMARY: Peripheral nerve damage is a significant clinical problem that can lead to severe complications in patients. Regarding the regeneration of peripheral nerves, it is crucial to use experimental animals' nerves and use different evaluation methods. Epineural or perineural suturing is the gold standard in treating sciatic nerve injury, but nerve repair is often unsuccessful. This study aimed to investigate the neuroregenerative effects of magnetotherapy and bioresonance in experimental animals with sciatic nerve damage. In this study, 24 female Wistar rats were divided into 7 groups (n=6) as follows: Group 1 (Control), Group 2 (Axonotmesis control), Group 3 (Anastomosis control), Group 4 (Axonotmesis + magnetotherapy), Group 5 (Anastomosis + magnetotherapy), Group 6 (Axonotmesis + bioresonance), Group 7 (Anastomosis + bioresonance). Magnetotherapy and bioresonance treatments were applied for 12 weeks. Behavioural tests and EMG tests were performed at the end of the 12th week. Then the rats were sacrificed, and a histopathological evaluation was made. The statistical significance level was taken as 5 % in the calculations, and the SPSS (IBM SPSS for Windows, ver.21) statistical package program was used for the calculations. Statistically significant results were obtained in animal behaviour tests, EMG, and pathology groups treated with magnetotherapy. There was no statistically significant difference in the groups treated with bioresonance treatment compared to the control groups. Muscle activity and nerve repair occurred in experimental animals with acute peripheral nerve damage due to 12 weeks of magnetotherapy, and further studies should support these results.

El daño a los nervios periféricos es un problema clínico importante que puede conducir a complicaciones graves en los pacientes. En cuanto a la regeneración de los nervios periféricos, es crucial utilizar los nervios de los animales de experimentación y diferentes métodos de evaluación. La sutura epineural o perineural es el gold estándar en el tratamiento de lesiones del nervio ciático, pero la reparación del nervio a menudo no tiene éxito. Este estudio tuvo como objetivo investigar los efectos neuroregenerativos de la magnetoterapia y la biorresonancia en animales de experimentación con daño del nervio ciático. En el estudio, 24 ratas hembras Wistar se dividieron en 7 grupos (n=6) de la siguiente manera: Grupo 1 (Control), Grupo 2 (Control de axonotmesis), Grupo 3 (Control de anastomosis), Grupo 4 (Axonotmesis + magnetoterapia), Grupo 5 (Anastomosis + magnetoterapia), Grupo 6 (Axonotmesis + biorresonancia), Grupo 7 (Anastomosis + biorresonancia). Se aplicaron durante 12 semanas tratamientos de magnetoterapia y biorresonancia. Las pruebas de comportamiento y las pruebas de EMG se realizaron al final de la semana 12. Luego se sacrificaron las ratas y se realizó una evaluación histopatológica. El nivel de significación estadística se tomó como 5 % en los cálculos, y se utilizó el programa de paquete estadístico SPSS (IBM SPSS para Windows, ver.21). Se obtuvieron resultados estadísticamente significativos en pruebas de comportamiento animal, EMG y grupos de patología tratados con magnetoterapia. No hubo diferencia estadísticamente significativa en los grupos con tratamiento de biorresonancia en comparación con los grupos controles. La actividad muscular y la reparación nerviosa, se produjeron en animales de experimentación con daño nervioso periférico agudo, debido a 12 semanas de magnetoterapia.Estudios adicionales deberían respaldar estos resultados.

Time-dependent proregenerative effects of exogenous melatonin on the transected sciatic nerve / Efectos proregenerativos dependientes del tiempo de la melatonina exógena en el nervio ciático seccionado

SUMMARY: Microsurgical procedures are the treatment of choice of peripheral nerve injuries, but often fail to reach full functional recovery. Melatonin has neuroprotective actions and might be used as a possible proregenerative pharmacological support. Therefore, the aim of this study was to analyze the time-dependence of the neuroprotective effect of melatonin on the overall fascicular structures of both ends of the transected nerve. Sciatic nerve transection was performed in 34 adult male Wistar rats divided in four groups: two vehicle groups (N=7) treated intraperitoneally for 7 (V7) or 21 (V21) consecutive days with vehicle (5 % ethanol in Ringer solution) and two melatonin groups (N=10) administered intraperitoneally 30 mg/kg of melatonin for 7 (M7) or 21 (M21) consecutive days. At the end of the experiment, proximal stump neuroma and distal stump fibroma were excised and processed for qualitative and quantitative histological analysis. Intrafascicular neural structures were better preserved and the collagen deposition was reduced in the melatonin treated groups than in the vehicle groups. Myelin sheath regeneration observed through its thickness measurement was statistically significantly (p<0,05) more pronounced in the M21 (1,23±0,18 µm) vs. V21 group (0,98±0,13 µm). The mean volume density of the endoneurium was lower in both melatonin treated groups in comparison to the matching vehicle treated groups. Although not statistically different, the endoneural tube diameter was larger in both melatonin groups vs. vehicle groups, and the effect of melatonin was more pronounced after 21 days (24,97 % increase) vs. 7 days of melatonin treatment (18,8 % increase). Melatonin exerts a time-dependent proregenerative effect on nerve fibers in the proximal stump and an anti-scarring effect in both stumps.

Los procedimientos microquirúrgicos son el tratamiento de elección de las lesiones de los nervios periféricos, pero a menudo no logran una recuperación funcional completa. La melatonina tiene acciones neuroprotectoras y podría ser utilizada como un posible apoyo farmacológico proregenerativo. Por lo tanto, el objetivo de este estudio fue analizar la dependencia del tiempo del efecto neuroprotector de la melatonina sobre las estructuras fasciculares generales de ambos extremos del nervio seccionado. La sección del nervio ciático se realizó en 34 ratas Wistar macho adultas divididas en cuatro grupos: dos grupos de vehículo (N=7) tratados por vía intraperitoneal durante 7 (V7) o 21 (V21) días consecutivos con vehículo (5 % de etanol en solución Ringer) y dos grupos grupos de melatonina (N=10) a los que se les administró por vía intraperitoneal 30 mg/kg de melatonina durante 7 (M7) o 21 (M21) días consecutivos. Al final del experimento, se extirparon y procesaron el neuroma del muñón proximal y el fibroma del muñón distal del nervio para un análisis histológico cualitativo y cuantitativo. Las estructuras neurales intrafasciculares se conservaron mejor y el depósito de colágeno se redujo en los grupos tratados con melatonina respecto a los grupos con vehículo. La regeneración de la vaina de mielina observada a través de la medición de su espesor fue estadísticamente significativa (p<0,05) más pronunciada en el grupo M21 (1,23±0,18 µm) vs V21 (0,98±0,13 µm). La densidad de volumen media del endoneuro fue menor en ambos grupos tratados con melatonina en comparación con los grupos tratados con vehículo equivalente. Aunque no fue estadísticamente diferente, el diámetro del tubo endoneural fue mayor en ambos grupos de melatonina frente a los grupos de vehículo, y el efecto de la melatonina fue más pronunciado después de 21 días (aumento del 24,97 %) frente a los 7 días de tratamiento con melatonina (18,8 % de aumento). La melatonina ejerce un efecto proregenerativo dependiente del tiempo sobre las fibras nerviosas del muñón proximal y un efecto anticicatricial en ambos muñones.

Effect of Tacrolimus and Cyclosporine Immunosuppressants on Peripheral Nerve Regeneration: Systematic Review and Meta-analysis / Efeito dos imunossupressores tacrolimus e ciclosporina na regeneração de nervos periféricos: Revisão sistemática e metanálises

Abstract Peripheral nerve damage is an important cause of seeking medical attention. It occurs when the continuity of structures is interrupted and the propagation of nervous impulses is blocked, affecting the functional capacity of individuals. To assess the effects of the immunosuppressants tacrolimus and cyclosporine on the regeneration of peripheral nerves, a systematic review of the literature was carried out. The articles included were published until September 2018 and proposed to evaluate the effects of the immunosuppressants tacrolimus and cyclosporine on nerve regeneration and neuroprotection, available in the MEDLINE, EMBASE, Cochrane Library, Web of Science, Oxford Pain Relief Database, and LILACS databases. The research analysed a total of 56 articles, of which 22 were included in the meta-analysis. Statistical analysis suggests the protective effect of tacrolimus in the regeneration of the number of myelinated axons (95% confidence interval [CI]: 0.93-2.39; p< 0.01); however, such effect was not observed in relation to cyclosporine (95%CI: - 0.38-1.18; p» 0.08) It also suggests that there is a significant relationship between the use of tacrolimus and myelin thickness (95%CI» 2.00-5.71; p< 0. 01). The use of immunosuppressants in the regeneration of peripheral nerve damage promotes an increase in the number of myelinated axons in general, regardless of the administered dose. In addition, it ensures greater myelin thickness, muscle weight and recovery of the sciatic functional index. However, heterogeneity was high in most analyses performed.

Resumo As lesões nervosas periféricas são uma causa importante de busca por atendimento médico. Elas ocorrem quando há a interrupção da continuidade das estruturas e do bloqueio da propagação dos impulsos nervosos, afetando a capacidade funcional dos indivíduos. Para avaliar os efeitos dos imunossupressores tacrolimus e ciclosporina na regeneração de nervos periféricos, foi realizada uma revisão sistemática da literatura. Foram incluídos artigos publicados até setembro de 2018, que se propunham avaliar os efeitos dos imunossupressores tacrolimus e ciclosporina na regeneração nervosa e neuroproteção, disponíveis nas bases de dados MEDLINE, EMBASE, Cochrane Library, Web of Science, Oxford Pain Relief Database e LILACS. A pesquisa analisou um total de 56 artigos, dos quais 22 foram para metanálise. A análise estatística sugere o efeito protetor do tacrolimus na regeneração do número de axônios mielinizados (intervalo de confiança [IC] 95%: 0,93-2,39; p< 0,01); todavia tal efeito não foi observado em relação à ciclosporina (IC95%: - 0,38-1,18; p» 0,08). Ela também sugere haver uma relação significativa entre o uso do tacrolimus e a espessura da mielina (IC95%: 2,00-5,71; p< 0,01). O uso de imunossupressores na regeneração de lesão nervosa periférica promove um aumento no número de axônios mielinizados de forma geral, independentemente da dose administrada. Além disso, garante uma maior espessura da mielina, um maior peso muscular e restabelecimento do índice da função do nervo ciático. Todavia, a heterogeneidade foi alta na maioria das análises realizadas.

Use of aerobic treadmill exercises on nerve regeneration after sciatic nerve injury in spontaneously hypertensive rats

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.

Morphometric study of rat sciatic nerve recovery after three nerve repair techniques: epineural suture, polyethylene glycol hydrogel and fibrin sealant / Estudio morfométrico de la recuperación del nervio ciático de rata después de tres técnicas de reparación nerviosa: sutura epineural, hidrogel de polietilenglicol y sellante de fibrina

SUMMARY: The effectiveness of microsurgical technique has a direct impact on the recovery of the injured peripheral nerve. The aim of our study was to investigate the result of sciatic nerve regeneration in rats after complete neurotomy and after nerve repair techniques including: 1) epineural suture; 2) polyethylene glycol hydrogel (PEG) (DuraSeal); 3) fibrin sealant (Tisseel). The cross-section of distal sciatic nerve was studied at 14th, 30th and 60th days after nerve repair. Morphometry of myelinated nerve fibers in the distal stump of the sciatic nerve was performed. A significant increase in the number of myelinated nerve fibers was found, especially between 14 and 30 days. The density of myelinated nerve fibers in the distal stump at day 60 was significantly higher after using nerve repair technique including PEG and fibrin versus epineural suture (29.2 % and 32.1 % versus 21.5 %, P <0.05), and a higher level of remyelination of nerve fibers observed in the group with PEG. On day 60, complete elimination of PEG and fibrin sealant was not observed, encapsulation was found around the clusters of hydrogel. Thereby, three peripheral nerve repair techniques were equally effective, only with the use of PEG remyelination of nerve fibers was increasing.

RESUMEN: La efectividad de la técnica microquirúrgica tiene un impacto directo en la recuperación del nervio periférico lesionado. El objetivo de nuestro estudio fue investigar el resultado de la regeneración del nervio ciático en ratas después de una neurotomía completa y después de técnicas de reparación nerviosa que incluyeron: 1) sutura epineural; 2) hidrogel de polietilenglicol (PEG) (DuraSeal); 3) sellante de fibrina (Tisseel). La sección transversal del nervio ciático distal se estudió a los 14, 30 y 60 días después de la reparación del nervio. Se realizó la morfometría de fibras nerviosas mielinizadas en el muñón distal del nervio ciático. Se observó un aumento significativo en el número de fibras nerviosas mielinizadas, especialmente entre los 14 y 30 días. La densidad de las fibras nerviosas mielinizadas en el muñón distal en el día 60 fue significativamente mayor después de usar una técnica de reparación nerviosa que incluye PEG y fibrina en comparación con la sutura epineural (29,2 % y 32,1 % versus 21,5 %, P <0,05), y un mayor nivel de remielinización del nervio en fibras observadas en el grupo con PEG. El día 60, no se observó la eliminación completa de PEG y sellador de fibrina, se encontró encapsulación alrededor de los grupos de hidrogel. Por lo tanto, tres técnicas de reparación de nervios periféricos fueron igualmente efectivas, solo que aumentaba la remielinización de fibras nerviosas con PEG.

Effects of Nogo-A and its receptor on the repair of sciatic nerve injury in rats

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.

Olfactory ensheathing cells in facial nerve regeneration / Células embainhantes olfatórias na regeneração do nervo facial

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.

Assessment of the Effects of Swimming as a Postoperative Rehabilitation on Nerve Regeneration of Wistar Rats Submitted to Grafting of Autologous Nerves after Injury to the Sciatic Nerve / Avaliação dos efeitos da natação como reabilitação pós-operatória na regeneração nervosa de ratos da linhagem Wistar submetidos a enxerto de nervos autólogos após lesão do nervo ciático

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.

High energy photobiomodulation therapy in the early days of injury improves sciatic nerve regeneration in mice / Aplicação de alta energia da terapia de fotobiomodulação nos primeiros dias de lesão otimiza a regeneração de nervo ciático em camundongos

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.

Caracterização físico-química e atividade biológica de um cimento dentário à base de quitosana, nanohidroxiapatita, nanopartículas de óxido de zinco para estimulação de células nervosas de Schwann (HS-SCH-2) / Physical-chemical characterization and biological activity of a dental cement based on chitosan, nano-hydroxyapatite, and zinc oxide nanoparticles for Schwann nervous cell stimulation (hs-sch-2)

Os cimentos dentários e ortopédicos são utilizados amplamente em diversas aplicações clínicas. Novos cimentos vêm sendo propostos visando à preservação ou regeneração tecidual. Contudo, pouco se conhece sobre o papel desses biomateriais na regeneração nervosa. As células mais comumente envolvidas na regeneração nervosa são as células de Schwann (SCs) sendo sua principal função o suporte aos axônios através da liberação de fatores de crescimento e isolamento axonal através da formação da bainha de mielina. Como estratégia da presente pesquisa, foi estudado um cimento à base da quitosana com adição de substâncias que podem atuar sinergicamente na resposta celular nervosa, tais como, as nanopartículas (NPs) de hidroxiapatita e o óxido de zinco, visto que têm propriedades bioativas e biocondutoras, além de promoverem a condução de prolongamento axonal. A doxiciclina (Dox) foi acrescida como antimicrobiano, potente inibidora de metaloproteinases (MMPs) e estimuladora da diferenciação celular no processo de regeneração tecidual. Assim, as propriedades físico-químicas e biológicas do cimento de nano-hidroxiapatita, quitosana, óxido de zinco e doxiciclina foram avaliadas, bem como a capacidade de promover um ambiente favorável para as células nervosas periféricas. Os cimentos foram caracterizados físico-químicamente mediante a determinação do pH, tempo de presa e solubilidade, lixiviação de íons cálcio, liberação controlada de doxiciclina, difração de Raios X, Termogravimetria (TG), espectroscopia Raman, molhabibidade, e testes de atividade biológica, para assim também serem avaliados em contato com células nervosas de Schwann (HS-Sch-2). O cimento apresentou pH neutro (7,0), tempo de presa de 5,7 ± 0,22 minutos, solubilidade menor que 3%, lixiviação de cálcio de 8,14 ± 0,71 mg L-1 após 14 dias, estabilidade térmica e a análise espectroscópica ratificou a presença e diferenciação das estruturas químicas dos componentes do cimento coerentemente com as imagens das análises microscópicas. Além disso, o cimento se mostrou hidrofílico, teve efeito hemolítico baixo (17%), obteve alta citocompabilidade celular em fibroblastos ATCC 3T3 (72%) e ação antimicrobiana. O cimento aumentou significativamente o crescimento das células de Schwann, 48,6% a mais do que o grupo controle (p≤0.05), e maior capacidade metabólica na análise mitótica quando em contato com este material (33%). Pode-se concluir que o cimento proposto à base de quitosana contendo hidroxiapatita e óxido de zinco nanoparticulados com adição de doxiciclina obteve efeito bioativo em células de Schwann promovendo, assim, o crescimento e a atividade mitótica celular, sendo então um biomaterial promissor para estudos de remielinização de nervos periféricos e regeneração nervosa in vivo.

Dental and orthopedic cements are used widely in several clinical applications. New cements have been proposed aimed the tissue preservation or regeneration. Nevertheless, nerve regeneration is not well known. The cells most commonly used in nerve regeneration are Schwann cells (SCs) which represent glial cells in the peripheral nervous system, their main function being supporting axons by releasing growth factors and axonal isolation through the formation of the myelin sheath. As a strategy of this research, chitosan-based cement was studied with the addition of substances that can act synergistically in the nervous cell response, such as the hydroxyapatite and zinc oxide nanoparticles (NPs), since they have bioactive and bioconductive properties; in addition to furthermore, they promote the conduction of axonal prolongation. Doxycycline (Dox) was added as an antimicrobial, a potent inhibitor of MMPs, a stimulator of cell differentiation in the tissue regeneration process. Thus, the physical-chemical and biological properties of nanohydroxyapatite, chitosan, zinc oxide and doxycycline cements were evaluated, as well as the ability to promote a favorable environment for peripheral nerve cells. Blocks of cements were characterized physically and chemically by determining pH, setting time and solubility, calcium ions leaching, controlled release of doxycycline, X-ray diffraction, Thermogravimetry (TG), Raman spectroscopy, wetness, and biological activity tests, so they can also be evaluated in contact with Schwann nerve cells (HS-Sch-2). The cement showed neutral pH (7.0), setting time of 5.7 ± 0.22 minutes, solubility less than 3%, calcium leaching of 8.14 ± 0.71 mg L-1 after 14 days, stability thermal and spectroscopic analysis confirmed the presence and differentiation of the chemical structures of the cement components coherently with the images of the microscopic analysis. In addition, the cement was shown to be hydrophilic, had a low hemolytic effect (17%), and obtained high cell cytocompatibility in ATCC 3T3 fibroblasts (72%) and antimicrobial action. The cement significantly increased the growth of Schwann cells, 48.6% more than the control group (p≤0.05), and greater metabolic capacity in the mitotic analysis when in contact with this material (33%). It can be concluded that the proposed chitosan-based cement containing hydroxyapatite and zinc oxide nanoparticulated with the addition of doxycycline has a bioactive effect in Schwann cells, thus promoting cell growth and mitotic activity, thus being a promising biomaterial for studies of remyelinization of peripheral nerves and nerve regeneration in vivo.

Stem cells in end-to-side neurorrhaphy. Experimental study in rats

Abstract Purpose: To evaluate the influence of mesenchymal stem cells from adipose tissue in the end-to-side neurorrhaphy, focusing in the nerve regeneration and the muscle reinnervation in acute trauma. Methods: 140 animals were randomly divided in seven groups: control, denervated, end-to-side neurorrhaphy between distal stump of common peroneal nerve and tibial nerve (ESN), ESN wrapped in fascia, ESN wrapped in fascia and platelet gel, ESN wrapped in platelet gel, ESN wrapped in fascia and platelet gel within stem cells (without culture) removed from the adipose tissue. Mass measurements of the animal and of cranial tibial muscles, electromyography, walking track analysis tests and histological examinations of the nerves and muscles after 180 days was performed. Results: In the groups where the ESN was performed, the results were always better when compared to the denervated group, showing reinnervation in all ESN groups. The most sensitive methods were walking track and histological analysis. Only the group with stem cells showed values similar to the control group, as well as the functional indices of peroneal nerve and the number of nerve fibers in the peroneal nerve. Conclusions: Stem cells were effective in ESN according with the functional index of the peroneal nerve, evaluated by walking track analysis and the number of nerve fibers in the peroneal nerve.

Criteria for assessing peripheral nerve injury. Behavioral and functional assessment in non-operated Wistar rats

Abstract Purpose To evaluate the normality pattern in functional tests of peripheral nerves. Methods Sixty female and sixty male Wistar rats were submitted to vibrissae movement and nictitating reflex for facial nerve; grooming test and grasping test for brachial plexus; and walking tracking test and horizontal ladder test for lumbar plexus. The tests were performed separately, with an interval of seven days between each. Results All animals showed the best score in vibrissae movement, nictitating reflex, grooming test, and horizontal ladder test. The best score was acquired for the first time in more than 90% of animals. The mean of strength on the grasping test was 133.46±12.08g for the right and 121.74±8.73g for the left anterior paw. There was a difference between the right and left sides. There was no difference between the groups according to sex. There is no statistical difference comparing all functional indexes between sex, independent of the side analyzed. The peroneal functional index showed higher levels than the sciatic and tibial functional index on both sides and sex. Conclusions The behavioral and functional assessment of peripheral nerve regeneration are low-cost, easy to perform, and reliable tests. However, they need to be performed by experienced researchers to avoid misinterpretation.

Mechanical properties of the sciatic nerve following combined transplantation of analytically extracted acellular allogeneic nerve and adipose-derived mesenchymal stem cells

Abstract Purpose To investigate the effects of Chemically Extracted Acellular Nerves (CEANs) when combined with Adipose-Derived mesenchymal Stem Cell (ADSC) transplantation on the repair of sciatic nerve defects in rabbits. Methods A total of 71 six-month-old Japanese rabbit were used in this study. Twenty rabbits served as sciatic nerve donors, while the other 51 rabbits were randomly divided into Autologous Nerve Transplantation Group (ANT, n=17), CEAN group (n=17) and CEAN-ADSCs group (n=17). In all these groups, the rabbit's left sciatic nerves were injured before the experiment, and the uninjured sciatic nerves on their right side were used as the control (CON). Electrophysiological tests were carried out and sciatic nerves were prepared for histomorphology and stretch testing at 24 weeks post-transplant. Results There were significant differences between ANT and Con groups in amplitude (AMP): P=0.031; motor nerve conduction velocity (MNCV): P=0.029; Maximum stress: P=0.029; and Maximum strain P=0.027. There were also differences between the CEAN and CEAN+ADSCs groups in AMP: P=0.026, MNCV: P=0.024; Maximum stress: P=0.025 and Maximum strain: P=0.030. No significant differences in these parameters were observed when comparing the ANT and CEAN+SACN groups (MNCV: P=0.071) or the CEAN and ANT groups (Maximum stress: P=0.069; Maximum strain P=0.077). Conclusion Addition of ADSCs has a significant impact on the recovery of nerve function, morphology, and tensile mechanical properties following sciatic nerve injury.

Monitorização de células-tronco mesenquimais injetadas via retrobulbar próximas ao nervo óptico lesados de coelhos / Monitoring of stem cells from adipose tissue injected via retrobulbar next to previously injured optic nerve of rabbits

Resumo Objetivo: Verificar a presença das células-tronco mesenquimais (MSC) na área próxima ao nervo óptico de coelhos previamente lesado com álcool absoluto. Métodos: Os 12 coelhos da raça Nova Zelândia foram distribuídos em 2 lotes. Após sedação, cada olho do animal recebeu uma injeção retrobulbar de 1 ml de álcool absoluto em um dos olhos e de 1 ml de solução fisiológica 0,9% (SF) no olho contralateral. Após 15 dias deste procedimento inicial todos os olhos dos animais pertencentes ao lote A, receberam via retrobulbar, uma solução contendo MSC de tecido adiposo humano e previamente marcadas com Qdots,. Todos os olhos dos animais do lote B receberam solução PBS. Resultados: Após 15 dias desta última aplicação os animais foram sacrificados e as lâminas foram analisadas. A presença das MSC foi observada em 100% dos olhos dos animais do lote A. Conclusão: Os resultados sugerem que a marcação prévia das MSC com Qdots permitiu o acompanhamento das mesmas na região aplicada e em áreas mais internas do nervo óptico. A permanência de MSC após 15 dias de aplicação ao redor do nervo óptico sugere a viabilidade e possível participação das mesmas no processo de regeneração do tecido lesado. Nas condições deste estudo, a via de aplicação retrobulbar permitiu a mobilização das células tronco do local de aplicação até áreas centrais dos nervos ópticos nos animais do lote A, sugerindo que esta poderá ser uma via de acesso eficaz para as MSC no processo de regeneração de neuropatias ópticas.

Abstract Obtective: To verify the presence of mesenchymal stem cells (MSC) in the area close to the optic nerve of previously injured with absolute alcohol. Methods: Twelve New Zealand breed rabbits were divided into two groups, and after sedation, each eye of the animal received a retrobulbar injection of 1 ml of absolute ethanol in one eye, and 1 ml of physiological solution 0.9 % (PS) in the contralateral eye. After 15 days all eyes of animals belonging to group A, received via retrobulbar a solution containing MSCs from human adipose tissue (AT) and previously marked with Qdots, while all eyes of animals from group B received solution containing PBS. Results: The presence of MSC was observed in 100% of the eyes of the animals of group A and the more central areas near and into the optic nerve. Conclusion: The results suggest that the appointment of MSC with Qdots allowed their follow-up applied in the region and in the inner areas of the optic nerve. The MSC permanence after 15 days of application around the optic nerve suggests the feasibility and possible involvement of the same during the damaged tissue regeneration process. Under the conditions of this study, the route of retrobulbar application and the presence of the stem cells to the central areas of the optic nerves in animals of group A, suggests that this might be an effective approach for MSCs in regeneration process of optic neuropathies.

Effects of growth hormone in the central nervous system

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

Eficácia da estimulação elétrica com corrente russa após neurorrafia término-lateral do nervo fibular comum: análise eletroneuromiográfica e de força muscular / Eficacia de la estimulación eléctrica con la corriente rusa tras la neurorrafia término-lateral del nervio fibular común: análisis electroneuromiográfico y de fuerza muscular muscular / Efficacy of electrical Russian current stimulation after end-to-side neurorrhaphy of the common fibular nerve: electroneuromyography and muscle strength analysis

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.

Serotonin induces or inhibits neuritic regeneration of leech CNS neurons depending on neuronal identity

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.

Sugarcane biopolymer as a guide tube in the regeneration of peripheral nerves in rats / Biopolímero de caña de azúcar como tubo guía en la regeneración de nervios periféricos en ratones

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.

Does neuroectodermal stem cells transplantation restore neural regeneration and locomotor functions in compressed spinal cord injury rat model? / ¿El trasplante de células madre neuroectodérmicas restaura la regeneración neural y las funciones locomotoras en el modelo de rata con lesión de la médula espinal comprimida?

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.