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.

Resultados de la neurólisis como tratamiento del dolor neuropático en pacientes con lesión del nervio ciático. Reporte de casos / Results of neurolysis for the treatment of neuropathic pain in patients with sciatic nerve Injury. Case report

Introducción: La lesión del nervio ciático puede ocasionar desde parestesias e hipoestesias, hasta dolor neuropático severo y parálisis. La neurólisis suele mejorar la función, el dolor y la calidad de vida de los pacientes. El objetivo de este estudio fue evaluar los resultados clínico-funcionales de una serie de pacientes con dolor neuropático por lesión del nervio ciático que no respondieron al tratamiento conservador y fueron sometidos a neurólisis. Materiales y métodos: Se analizó retrospectivamente una serie de pacientes sometidos a neurólisis del nervio ciático mayor entre marzo de 2009 y junio de 2018. El dolor pre- y posoperatorio se evaluó mediante la escala analógica visual y la escala de Likert. El tipo de dolor posoperatorio se evaluó con el cuestionario DN4 y la calidad de vida relacionada con la salud, con el cuestionario SF-36.Resultados:Se incluyó a 8 pacientes. A los 32 meses de seguimiento promedio (rango 14-66), el dolor había mejorado notablemente (promedio de 3 y 1,88 puntos en las escalas analógica visual y de Likert, respectivamente). El cuestionario DN4 arrojó un promedio de 3,75 puntos (rango 2-7). Según el SF-36, la "salud física" fue la variable con peores resultados (promedio 30,15).Conclusiones: La neurólisis, cuando se indica a pacientes con mala respuesta al tratamiento conservador, es un método que alivia el dolor y mejora la calidad de vida de los pacientes con dolor neuropático secundario a una lesión del nervio ciático. Nivel de Evidencia: IV

Introduction: Sciatic nerve injury may cause paresthesias and hypoesthesias, severe neuropathic pain, and paralysis. Neurolysis can improve function, pain, and quality of life for these patients. The objective of this paper is to evaluate the clinical-functional outcomes of a series of patients with neuropathic pain due to sciatic nerve injury that was refractory to conservative treatment in whom neurolysis was performed. materials and methods:A retrospective case series of patients operated on for neurolysis of the greater sciatic nerve between March 2009 and June 2018 was analyzed. Preoperative and postoperative pain were evaluated using the visual analog scale (VAS) and the Likert scale. The type of postoperative pain was evaluated using the DN4 questionnaire, and the health-related quality of life was measured with the SF-36 questionnaire. Results: Eight patients were included. All patients evolved with a notable improvement in pain, with an average of 3 and 1.88 points on the VAS and Likert scales, respectively. The mean follow-up was 32 months (range 14­66). The DN4 questionnaire showed an average of 3.75 points (range 2­7). According to the SF-36, "Physical Health" was the variable with the worst results, with an average of 30.15. Conclusions: Sciatic nerve neurolysis in patients with neuropathic pain due to sciatic nerve injury and poor response to conservative treatment may improve pain and quality of life. Level of Evidence: IV

Alleviation of neuropathic pain by trazodone in rats

Abstract Neuropathic pain is generally characterised by an abnormal sensation (dysesthesia), an increased response to painful stimuli (hyperalgesia), and pain in response to a stimulus that does not normally provoke pain (allodynia). The present study was designed to investigate the effect of trazodone (5mg/kg and 10mg/kg) on peripheral neuropathic pain induced by partial sciatic nerve ligation in rats. Mechanical hyperalgesia, cold allodynia and thermal hyperalgesia were assessed by performing the pinprick, acetone, and hot plate tests, respectively. Biochemically, lipid peroxidation level and total calcium levels were measured. However, trazodone administration (5 and 10 mg/ kg i.p.) for 21days significantly diminished partial sciatic nerve ligation-induced neuropathic pain along with areduction in oxidative stress and calcium levels. The results of the present study suggest that trazodone is effective in attenuating partial sciatic nerve ligation-inducedpainful neuropathic states, which may be attributed to decreased oxidative stress and calcium levels.

Local vibration therapy promotes the recovery of nerve function in rats with sciatic nerve injury / 中西医结合学报

OBJECTIVE@#It has been reported that local vibration therapy can benefit recovery after peripheral nerve injury, but the optimized parameters and effective mechanism were unclear. In the present study, we investigated the effect of local vibration therapy of different amplitudes on the recovery of nerve function in rats with sciatic nerve injury (SNI).@*METHODS@#Adult male Sprague-Dawley rats were subjected to SNI and then randomly divided into 5 groups: sham group, SNI group, SNI + A-1 mm group, SNI + A-2 mm group, and SNI + A-4 mm group (A refers to the amplitude; n = 10 per group). Starting on the 7th day after model initiation, local vibration therapy was given for 21 consecutive days with a frequency of 10 Hz and an amplitude of 1, 2 or 4 mm for 5 min. The sciatic function index (SFI) was assessed before surgery and on the 7th, 14th, 21st and 28th days after surgery. Tissues were harvested on the 28th day after surgery for morphological, immunofluorescence and Western blot analysis.@*RESULTS@#Compared with the SNI group, on the 28th day after surgery, the SFIs of the treatment groups were increased; the difference in the SNI + A-2 mm group was the most obvious (95% confidence interval [CI]: [5.86, 27.09], P < 0.001), and the cross-sectional areas of myocytes in all of the treatment groups were improved. The G-ratios in the SNI + A-1 mm group and SNI + A-2 mm group were reduced significantly (95% CI: [-0.12, -0.02], P = 0.007; 95% CI: [-0.15, -0.06], P < 0.001). In addition, the expressions of S100 and nerve growth factor proteins in the treatment groups were increased; the phosphorylation expressions of ERK1/2 protein in the SNI + A-2 mm group and SNI + A-4 mm group were upregulated (95% CI: [0.03, 0.96], P = 0.038; 95% CI: [0.01, 0.94], P = 0.047, respectively), and the phosphorylation expression of Akt in the SNI + A-1 mm group was upregulated (95% CI: [0.11, 2.07], P = 0.031).@*CONCLUSION@#Local vibration therapy, especially with medium amplitude, was able to promote the recovery of nerve function in rats with SNI; this result was linked to the proliferation of Schwann cells and the activation of the ERK1/2 and Akt signaling pathways.

Transcriptome Analysis of Schwann Cells at Various Stages of Myelination Implicates Chromatin Regulator Sin3A in Control of Myelination Identity / 神经科学通报·英文版

Enhancing remyelination after injury is of utmost importance for optimizing the recovery of nerve function. While the formation of myelin by Schwann cells (SCs) is critical for the function of the peripheral nervous system, the temporal dynamics and regulatory mechanisms that control the progress of the SC lineage through myelination require further elucidation. Here, using in vitro co-culture models, gene expression profiling of laser capture-microdissected SCs at various stages of myelination, and multilevel bioinformatic analysis, we demonstrated that SCs exhibit three distinct transcriptional characteristics during myelination: the immature, promyelinating, and myelinating states. We showed that suppressor interacting 3a (Sin3A) and 16 other transcription factors and chromatin regulators play important roles in the progress of myelination. Sin3A knockdown in the sciatic nerve or specifically in SCs reduced or delayed the myelination of regenerating axons in a rat crushed sciatic nerve model, while overexpression of Sin3A greatly promoted the remyelination of axons. Further, in vitro experiments revealed that Sin3A silencing inhibited SC migration and differentiation at the promyelination stage and promoted SC proliferation at the immature stage. In addition, SC differentiation and maturation may be regulated by the Sin3A/histone deacetylase2 (HDAC2) complex functionally cooperating with Sox10, as demonstrated by rescue assays. Together, these results complement the recent genome and proteome analyses of SCs during peripheral nerve myelin formation. The results also reveal a key role of Sin3A-dependent chromatin organization in promoting myelinogenic programs and SC differentiation to control peripheral myelination and repair. These findings may inform new treatments for enhancing remyelination and nerve regeneration.

Síndrome do piriforme: diagnóstico e tratamento: um estudo retrospectivo / Piriformis syndrome: diagnosis and treatment: a retrospective study

Introdução: A síndrome do piriforme (SP) é uma causa de dor ciática pouco entendida e conhecida, por isso, subdiagnosticada. Possui múltiplas possibilidades etiológicas e a abordagem terapêutica corrente privilegia o tratamento conservador. Objetivo: Neste estudo retrospectivo são destacados o diagnóstico, a etiologia, o diagnóstico diferencial e analisados os resultados do tratamento instituído. Métodos: 34 casos com seguimento mínimo de seis meses e máximo de 12 meses avaliados por uma escala simplificada de graduação de sintomas. Resultados: O tratamento clínico-conservador obteve excelentes resultados em 23 pacientes (67,6%), bom em nove pacientes (26,4%) e razoáveis (insatisfatórios) em dois pacientes (5,8%). Conclusões: Na dor com característica ciática, contínua ou intermitente e sem evidências de compressão radicular ou herniação discal lombar, deve-se pesquisar a possibilidade de síndrome do piriforme como um diagnóstico eminentemente clínico e de exclusão. O tratamento conservador apresenta resultados satisfatórios na maioria dos casos e a indicação cirúrgica está reservada como último recurso às falhas da terapia conservadora.

Introduction: Piriformis syndrome is a cause of sciatalgy barely understood and frequently unrecognized. It has multiple possible etiologic factors and the treatment of option is largely conservative. Objective: In this retrospective study, the diagnostic signs, the ethiology, the diferential diagnosis and the treatment results are discussed. Methods: 34 patients were followed-up for 6-12 months and evaluated by a simplified symptom rating scale. Results: Excellent results in 23 patients (67,6%), good in 9 patients (26,4%) and fair (unsatisfactory) in 2 patients (5,8%). Conclusions: In patients with sciatic pain without proved rachidian or discal lumbar disease, the possibility of Piriformis Syndrome must be investigated mainly by proper clinical examination and seen as a diagnosis of exclusion. The conservative treatment has satisfactory outcomes in most of cases and surgical procedure is reserved as a last resort in case of failure of the conservative management.

Comparison of two volumes for sciatic perineural injection using 1% methylene blue in rabbit cadavers / [Comparação de dois volumes para injeção perineural no nervo isquiático utilizando azul de metileno 1% em cadáveres de coelhos]

The purpose of this study was to assess the efficacy of a blind technique for sciatic and femoral nerve block in rabbit cadavers by evaluating the spread of 1% methylene blue at two different volumes. Nine recently euthanized rabbits weighing 2.5(0.3kg were used. The sciatic (SN) and femoral (FN) nerves of each limb were randomly assigned for injection with 1% methylene blue at 0.2mL/kg (G0.2) or 0.3mL/kg (G0.3). Nerves were dissected and measured for depth and extension of staining (cm). Mean comparisons were performed using paired t test. The relation between volume and nerve staining ( 2cm was assessed using chi-square test. The mean depth of SN was 1.9±0.2 and 1.6±0.3cm and staining 1.9±1.4 and 2.0±1.2cm, respectively in G0.2 and G0.3. No relation was found between depth and dye spread and there was no association between nerve staining ( 2.0cm and volume of solution. The FN failed to be stained in all subjects. In conclusion, SN injection can be successfully performed without guidance in rabbits. The lower volume (0.2mL/kg) is recommended to avoid systemic toxicity.(AU)

O objetivo deste estudo foi avaliar a eficácia de uma técnica para bloqueio às cegas dos nervos isquiático e femoral em cadáveres de coelhos, por meio da avaliação da dispersão de azul de metileno 1% em dois volumes distintos. Nove coelhos recém-eutanasiados, com peso 2,5(0,3kg, foram utilizados. Os nervos isquiático (NI) e femoral (NF) de cada membro foram aleatoriamente designados para injeção com azul de metileno 1% a 0,2mL/kg (G0,2) ou 0,3mL/kg (G0,3). Em seguida, foram dissecados e mensurados em relação à sua profundidade e extensão corada (cm). As médias foram comparadas por meio de teste t pareado. A relação entre volume e extensão corada ( 2cm foi avaliada utilizando-se teste de qui-quadrado. A profundidade média do NI foi 1,9±0,2 e 1,6±0,3cm, e a extensão corada 1,9±1,4 e 2,0±1,2cm, respectivamente, no G0,2 e no G0,3. Não houve relação entre a profundidade e a extensão corada ou entre a extensão corada ( 2,0cm e o volume de solução. Não foi observada coloração do NF em nenhum cadáver. Concluiu-se que a injeção do NI pode ser realizada com sucesso sem auxílio de tecnologias em coelhos. O menor volume (0,2mL/kg) é recomendado para evitar toxicidade sistêmica.(AU)

Lesión del nervio ciático mayor por proyectil de escopeta / Lesion of the major sciatic nerve due to a shotgun projectile

Se describe el caso clínico de un paciente de 26 años de edad, atendido en la consulta de Ortopedia y Traumatología del Centro de Diagnóstico Integral Salvador Allende de Caracas, en la República Bolivariana de Venezuela, quien desde hacía 6 meses había recibido un disparo de escopeta en la cara posterior de ambos muslos. Esta vez acudió a consulta con dolor intenso en el miembro inferior izquierdo, sobre todo por debajo de la rodilla, acompañado de parestesias en la zona de inervación de ambas ramas de bifurcación del nervio ciático. Se pudo comprobar que el joven presentaba múltiples impactos de proyectiles en la cara posterior de ambos muslos y marcha claudicante. Los estudios radiográficos confirmaron la presencia de 8 proyectiles, 2 en el muslo derecho y 6 en el izquierdo. En la vista lateral se observó que uno de ellos se encontraba a una profundidad que se correspondía con la región anatómica del nervio ciático izquierdo. Para la intervención quirúrgica se utilizó anestesia local, sedación y un intensificador de imágenes. Con la cooperación del paciente se pudo extraer el proyectil alojado en el epineuro del ciático sin complicaciones. A los 3 meses habían desaparecido las molestias y pudo reincorporarse a sus actividades habituales.

The case report of a 26 years patient is described. He was assisted in the Orthopedics and Traumatology Service of Salvador Allende Integral Diagnostic Center from Caracas, in the Bolivian Republic of Venezuela who had received a shotgun shot in the posterior face of both thighs 6 months ago. This time he went to visit the doctor with intense pain in the left inferior member, mainly below the knee, accompanied by paresthesias in the innervation area of both bifurcation branches of the sciatic nerve. It could be demonstrated that the young man presented multiple projectile impacts in the posterior face of both thighs and hesitating gait. The radiographic studies confirmed the presence of 8 projectiles, two in the right thigh and 6 in the left one. In the lateral view it was observed that one of them was at a depth that matched with the anatomical region of the left sciatic nerve. Local anesthesia, sedation and an images intensifier were used for the operation. The projectile located in the epineurium of the sciatic nerve could be removed with the patient cooperation without complications. After 3 months the discomfort had disappeared and he could return to his usual activities.

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.

Effect of creatine and sildenafil citrate on the physical performance of mice / Efecto de la creatina y del citrato de sildenafil sobre el desempeño físico de ratones / Efeito da creatina e do citrato de sildenafila sobre o desempenho físico de camundongos

ABSTRACT Introduction: The use of substances to enhance sports performance among professional and amateur athletes is increasing. Such substances may either be included in the group of dietary supplements or fall into pharmacological classes. Every substance used for this purpose is called an ergogenic agent. The number of ergogenic options available increases every day, favoring overuse and use without proper guidance. Among the dietary supplements, we highlight the use of creatine, a substance widespread in sports. Among the pharmacological groups, many drugs are used. Recently the use of sildenafil citrate by professional athletes from various predominantly aerobic sports modalities was reported in the media. Objective: To compare and demonstrate the responses caused by physical training associated with the use of creatine and sildenafil citrate in mice. Methods: A swim training protocol was applied and then an electrophysiograph was used in order to obtain parameters related to contraction intensity, the area under the curve and the percentage drop. Results: The responses obtained demonstrated the ergogenic action of creatine because it altered the parameters used for measurement. The use of sildenafil citrate did not yield satisfactory results to frame the drug as an ergogenic agent. Conclusion: Creatine has an ergogenic effect, reducing the percentage drop after 10 seconds, while sildenafil demonstrated no ergogenic potential and, interestingly, resulted in weaker responses when compared to the exercise groups. Evidence level II; Comparative prospective study .

RESUMEN Introducción: El uso de sustancias con el objetivo de aumentar el rendimiento deportivo entre atletas profesionales y amateurs es creciente. Tales sustancias pueden formar parte del grupo de suplementos alimentarios o integrar clases farmacológicas. Toda sustancia empleada para ese fin es denominada agente ergogénico. El número de opciones entre los agentes ergogénicos aumenta cada día, favoreciendo así su uso excesivo y sin la debida orientación. Entre los suplementos alimentarios, se destaca el uso de creatina, sustancia muy difundida en el medio deportivo. Ya entre los grupos farmacológicos, muchas sustancias son usadas. Recientemente, fue divulgado entre los medios de comunicación el uso de citrato de sildenafil por atletas profesionales, de varias modalidades deportivas, predominantemente las aeróbicas. Objetivos: Comparar y demostrar las respuestas ocasionadas por el entrenamiento físico, asociadas al uso de creatina y citrato de sildenafil en ratones. Métodos: Se aplicó un protocolo de entrenamiento de natación y, a continuación, se usó un electrofisiógrafo con el objetivo de obtener parámetros referentes a la intensidad de contracción, al área bajo la curva y a la caída porcentual. Resultados: Las respuestas obtenidas demuestran acción ergogénica de la creatina, visto que alteraron los parámetros empleados para la medición. Ya el uso de citrato de sildenafil no presentó resultados satisfactorios para encuadrar al fármaco como agente ergogénico. Conclusión: La creatina presenta efecto ergogénico porque reduce la caída porcentual después de 10 segundos, mientras que el sildenafil no presentó potencial ergogénico y, curiosamente, demostró respuestas inferiores cuando comparado a los grupos de ejercicio. Nivel de evidencia II; Estudio prospectivo comparativo .

RESUMO Introdução: O uso de substâncias com o objetivo de aumentar o rendimento esportivo entre atletas profissionais e amadores é crescente. Tais substâncias podem fazer parte do grupo de suplementos alimentares ou integrar classes farmacológicas. Toda substância empregada para esse fim é denominada de agente ergogênico. O número de opções entre os agentes ergogênicos aumenta a cada dia, favorecendo assim o uso em demasia e sem a devida orientação. Entre os suplementos alimentares, salientamos a utilização de creatina, substância muito difundida no meio esportivo. Já entre os grupos farmacológicos, muitas substâncias são utilizadas. Recentemente, foi divulgado entre os meios de comunicação o uso de citrato de sildenafila por atletas profissionais de várias modalidades esportivas, predominantemente as aeróbicas. Objetivos: Comparar e demonstrar as repostas ocasionadas pelo treinamento físico, associadas ao uso de creatina e citrato de sildenafila em camundongos. Métodos: Aplicou-se um protocolo de treinamento de natação e, a seguir, empregou-se um eletrofisiógrafo com objetivo de obter parâmetros referentes à intensidade de contração, à área sob a curva e à queda percentual. Resultados: As respostas obtidas demonstram ação ergogênica da creatina, visto que alteraram os parâmetros empregados para a mensuração. Já a utilização de citrato de sildenafila não apresentou resultados satisfatórios para enquadrar o fármaco como agente ergogênico. Conclusão: A creatina apresenta efeito ergogênico porque reduz a queda percentual após 10 segundos, já a sildenafila não apresentou potencial ergogênico e, curiosamente, demonstrou respostas inferiores quando comparado aos grupos de exercício. Nível de evidência II; Estudo prospectivo comparativo .

Anatomic landmarks for a safe arthroscopic approach to the deep gluteal space: a cadaveric study / Hitos anatómicos para un abordaje artroscópico seguro del espacio glúteo profundo: un estudio cadavérico

SUMMARY: To determine the morphometric landmarks and anatomical variants relevant to the arthroscopic approach to the deep gluteal space. Twenty deep gluteal spaces from cadaveric specimens were dissected. The anatomical variants of the sciatic nerve (SN) were determined according to the Beaton and Anson classification. A morphometric study of the distances in the subgluteal space was carried out to define the anatomical references to achieve a safe arthroscopic approach for piriformis syndrome [GT-SN=Distance from greater trochanter (GT) to SN emergence; GT-IT=Distance from GT to ischial tuberosity (IT); GT-IGA=distance from GT to inferior gluteal artery (IGA) emergence; IT-SN=distance from IT to SN emergence; IT-IGA=distance from IT to IGA]. The SN showed the most frequent anatomical pattern with an undivided nerve coming out of the pelvis below the piriformis muscle (Beaton type A) in 16 specimens (80 %). The common peroneal nerve emergence in the subgluteal space through the piriformis muscle (PM) with the tibial nerve being located at the lower margin of the piriformis muscle (Beaton type B) was observed in 4 specimens (20 %). The morphometric measurements of the surgical area of study were: GT-SN=7.23 cm (±8.3); GT-IT=8.56 cm (±0.1); GT-IGA=8.46 cm (±0.97); IT-SN=5.28 cm (±0.73), IT- IGA=5.47 cm (±0.74). When planning surgery for the deep gluteal syndrome in adult patients, the fact that the emergence of the SN in the subgluteal space is approximately 7 cm from the greater trochanter and 5 cm from the ischial tuberosity must be considered.

RESUMEN: El objetivo del estudio fue determinar referentes morfométricos y variantes anatómicas relevantes en el abordaje artroscópico del espació subglúteo. Se disecaron veinte regiones glúteas procedentes de cadáver. Las variaciones anatómicas del nervio ciático (SN) se determinaron de acuerdo con la clasificación de Beaton y Anson. Se llevó a cabo un estudio morfométrico de distancias en el espacio subglúteo, con objeto de determinar referencias que permitan un abordaje artroscópico seguro del sindrome piriforme [GT-SN= distancia trocánter mayor (GT) a la emergencia del nervio ciático (SN); GT-IT= distancia GT a la tuberosidad isquiática (IT); GT-IGA= distancia GT a la emergen- cia de la arteria glútea inferior (IGA); IT-SN= distancia IT a la emergencia del SN; IT-IGA= distancia IT a la IGA]. El patrón más frecuente del SN fue su emergencia no dividida por el margen inferior del músculo piriforme (tipo A Beaton) en 16 especímenes (80 %). La salida del nervio fibular común a través del músculo piriforme (PM) con el nervio tibial localizado en el margen inferior del PM (tipo B Beaton) se observó en 4 especímenes (20 %). Las medidas en el área quirúrgica de estudio fueron: GT-SN= 7,23 cm ± 8,3; GT-IT= 8,56 cm ± 0,1; GT-IGA= 8,46 cm ± 0,97; IT-SN= 5,28 cm ± 0,73 IT-IGA= 5,47 cm ± 0,74. En la cirugía del síndrome glúteo profundo en adultos, debe considerarse que la sa- lida del SN hacia el espacio subglúteo tiene lugar aproximadamente a 7 cm del GT y a 5 cm de la IT.

Neurofibroma plexiforme gigante del nervio ciático en una adulta burkinesa / Giant plexiform neurofibroma of the sciatic nerve in a Burkinabé adult

Se presenta el caso de una paciente de 36 años de edad con antecedente patológico de enfermedad de Von Reklinghausen, quien fue asistida en el Servicio de Cirugía General del Centro Hospitalario de Kossodô en Burkina Faso por presentar un tumor gigante en la región posterior del muslo derecho. Los exámenes complementarios confirmaron el presunto diagnóstico de neurofibroma plexiforme gigante del nervio ciático. Durante el procedimiento quirúrgico se extirpó un tumor infrecuente cuyo peso excedió los 22,5 kg. Con el tratamiento rehabilitador posoperatorio del miembro operado la paciente evolucionó satisfactoriamente y se le dio el alta hospitalaria 7 días después.

The case report of a 36 years patient with pathological history of Von Reklinghausen disease is presented. She was assisted in the General Surgery Service of the Hospital Center from Kossodô in Burkina Faso presenting a giant tumor in the back region of the right thigh. The complementary exams confirmed the presumed diagnosis of giant plexiform neurofibroma of the sciatic nerve. During the surgical procedure an uncommon tumor was removed which weight exceeded the 22.5 kg. With the postoperative rehabilitative treatment of the operated member the patient had a favorable clinical course and she was discharged from the hospital 7 days later.

Diagnóstico clínico de la incontinencia pigmentaria en dos neonatos con lesiones cutáneas vesículo-pustulosas / Clinical diagnosis of pigment incontinence in two neonates with vesicle-pustulous skin lesions

Introducción: La incontinencia pigmentaria es un trastorno neuroectodérmico sistémico que en el recién nacido se diagnostica por la presencia de lesiones cutáneas de tipo eritemato-vesiculosas o vesículo-pustulosas, con distribución según las líneas de Blaschko, asociadas a eosinofilia en muestra de sangre. Objetivo: Mostrar que es factible diagnosticar la incontinencia pigmentaria en el período neonatal, aún en casos esporádicos, mediante un adecuado ejercicio del método clínico. Presentación de los casos: Se trata de dos recién nacidas femeninas, nacidas a término, con peso adecuado para la edad gestacional y sin antecedentes pre- y perinatales de interés; la primera de las cuales se presenta al tercer día de nacida con lesiones en piel, de aspecto vesículo-pustuloso, que seguían el recorrido del nervio ciático poplíteo externo. El segundo caso se presenta al 11no día de nacida con lesiones de tipo vesículo-ampulosas, en región externa de los cuatro miembros, con mejoría a los 26 días de vida. En ambos casos se plantea el diagnóstico de incontinencia pigmentaria esporádica. Conclusiones: El diagnóstico de la incontinencia pigmentaria en el período neonatal constituye un reto, el cual es posible asumir si se lleva a cabo un adecuado uso del método clínico, con un minucioso diagnóstico diferencial. Para el diagnóstico, resulta útil establecer consenso a partir de un enfoque multidisciplinario(AU)

Introduction: Pigment incontinence is a systemic neuroectodermal disorder that in the newborn is diagnosed by the presence of skin lesions of erythematous-vesiculosus or vesicle-pustulous type, with distribution according to the Blaschko lines, associated with eosinophilia in the blood sample. Objective: Show that it is feasible to diagnose pigment incontinence in the neonatal period, even in sporadic cases, through proper performance of the clinical method. Presentation of cases: These are two female newborns, born full-term, with a suitable weight for gestational age and without a pre- and perinatal history of interest; the first case occurs on the third day of life, presenting skin lesions, vesicle-pustulous in appearance, which followed the path of the external popliteal sciatic nerve. The second case occurs on the 11th day of life with vesicle-ampulose lesions in the outer region of the four limbs, with improvement at 26 days of life. Diagnosis of sporadic pigment incontinence is stated in both cases. Conclusions: Diagnosing pigment incontinence in the neonatal period is a challenge, which can be assumed if proper use of the clinical method is carried out, with a thorough differential diagnosis(AU)

Endometriosis con infiltración aislada del nervio ciático, una forma de presentación atípica: reporte de un caso clínico / Isolated infiltrative endometriosis of the sciatic nerve, an atypical presentation: clinical case report

INTRODUCCIÓN: La endometriosis afecta hasta un 10-15% de las mujeres jóvenes. Se define como tejido endometrial funcional fuera de la cavidad uterina y su presentación clásica es la dismenorrea. La variedad profunda afecta a un 1-2% y las localizaciones más frecuentes son el peritoneo pélvico, ovarios, ligamentos útero-sacros y septum recto-vaginal; sin embargo, puede presentarse de forma muy infrecuente como implantes aislados localizados en relación al nervio ciático. El diagnóstico habitualmente es complejo y tardío, dado que los síntomas son inespecíficos y el examen físico puede ser indistinguible de otras etiologías. El estudio imagenológico de elección para la endometriosis profunda es la resonancia magnética (RM) de pelvis ya que una adecuada localización pre-quirúrgica de las lesiones es fundamental. CASO CLÍNICO: Paciente de sexo femenino de 46 años, con tres años de dolor pélvico, dismenorrea y dispareunia. El síntoma cardinal fue dolor ciático progresivo, con déficit motor y alteraciones sensitivas, los cuales se exacerbaban durante la menstruación y no presentaban respuesta al tratamiento farmacológico. En la RM se identifica nódulo sólido sospechoso de endometriosis en relación al nervio ciático derecho. El caso es evaluado por un comité multidisciplinario y se realiza cirugía laparoscópica. El diagnóstico de sospecha es confirmado histológicamente. La paciente presenta buena recuperación post-quirúrgica y cese completo de los síntomas descritos. DISCUSIÓN: La endometriosis profunda presenta un reto diagnóstico y habitualmente es tardío. Este caso presenta el resultado exitoso de una buena sospecha clínica, un estudio imagenológico completo y la resolución con una técnica quirúrgica compleja.

INTRODUCTION: Endometriosis is a disease that affects 10-15% of young women. It is characterized as functional endometrial tissue outside the uterine cavity. The most common form of presentation is dysmenorrhea. Deep endometriosis affects 1-2% of the patients, and is frequently located in the pelvic peritoneum, ovaries, utero-sacral ligaments and recto-vaginal septum. The isolated endometriosis of the sciatic nerve is a very uncommon presentation of this disease. Late diagnosis is frequent, mainly because the symptoms are non-specific, and the physical examination may be indistinguishable from other etiologies. The imaging study of choice is the pelvic magnetic resonance imaging (MRI) and an accurate pre-surgical location of the lesions is critical for a successful surgical outcome. CLINICAL CASE: 46-year-old female patient with 3 years of pelvic pain, dysmenorrhea and dyspareunia. The cardinal symptom was progressive sciatic pain, with motor deficit and sensory alterations. The pain was persistent despite pharmacological treatment and exacerbated during menstruation. MRI identifies a nodule located in the pelvic portion of the right sciatic nerve, suggestive of an endometriosis implant. The case was discussed by a multidisciplinary committee and laparoscopic surgery was performed. The diagnosis was confirmed with histology. The patient recovered well from surgery with significant improvement of the previously described symptoms. DISCUSSION: The diagnosis of deep endometriosis is challenging and usually delayed. This rare disease had a successful outcome, due to an early clinical suspicion, a thorough imaging study and an effective resolution with a complex surgical technique.

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.

The absence of piriformis muscle, combined muscular fusion, and neurovascular variation in the gluteal region

The gluteal region contains important neurovascular and muscular structures with diverse clinical and surgical implications. This paper aims to describe and discuss the clinical importance of a unique variation involving not only the piriformis, gluteus medius, gluteus minimus, obturator internus, and superior gemellus muscles, but also the superior gluteal neurovascular bundle, and sciatic nerve. A routine dissection of a right hemipelvis and its gluteal region of a male cadaver fixed in 10% formalin was performed. During dissection, it was observed a rare presentation of the absence of the piriformis muscle, associated with a tendon fusion between gluteus and obturator internus, and a fusion between gluteus minimus and superior gemellus muscles, along with an unusual topography with the sciatic nerve, which passed through these group of fused muscles. This rare variation stands out with clinical manifestations that are not fully established. Knowing this anatomy is essential to avoid surgical iatrogeny.

Effects of vitamin D administration on nociception and spinal cord pro-oxidant and antioxidant markers in a rat model of neuropathic pain

Reactive oxygen species (ROS) are involved in neuropathic pain, a complicated condition after nerve tissue lesion. Vitamin D appears to improve symptoms of pain and exhibits antioxidant properties. We investigated the effects of oral administration of vitamin D3, the active form of vitamin D, on nociception, the sciatic functional index (SFI), and spinal cord pro-oxidant and antioxidant markers in rats with chronic constriction injury (CCI) of the sciatic nerve, a model of neuropathic pain. Vitamin D3 (500 IU/kg per day) attenuated the CCI-induced decrease in mechanical withdrawal threshold and thermal withdrawal latency (indicators of antinociception) and SFI. The vitamin prevented increased lipid hydroperoxide levels in injured sciatic nerve without change to total antioxidant capacity (TAC). Vitamin D3 prevented increased lipid hydroperoxide, superoxide anion generation (SAG), and hydrogen peroxide (H2O2) levels in the spinal cord, which were found in rats without treatment at 7 and 28 days post-CCI. A significant negative correlation was found between mechanical threshold and SAG and between mechanical threshold and H2O2 at day 7. Vitamin D3 also prevented decreased spinal cord total thiols content. There was an increase in TAC in the spinal cord of vitamin-treated CCI rats, compared to CCI rats without treatment only at 28 days. No significant changes were found in body weight and blood parameters of hepatic and renal function. These findings demonstrated, for first time, that vitamin D modulated pro-oxidant and antioxidant markers in the spinal cord. Since antinociception occurred in parallel with oxidative changes in the spinal cord, the oxidative changes may have contributed to vitamin D-induced antinociception.

Claudin 14/15 play important roles in early wallerian degeneration after rat sciatic nerve injury / 中华创伤杂志(英文版)

PURPOSE@#Wallerian degeneration (WD) is an antegrade degenerative process distal to peripheral nerve injury. Numerous genes are differentially regulated in response to the process. However, the underlying mechanism is unclear, especially the early response. We aimed at investigating the effects of sciatic nerve injury on WD via CLDN 14/15 interactions in vivo and in vitro.@*METHODS@#Using the methods of molecular biology and bioinformatics analysis, we investigated the molecular mechanism by which claudin 14/15 participate in WD. Our previous study showed that claudins 14 and 15 trigger the early signal flow and pathway in damaged sciatic nerves. Here, we report the effects of the interaction between claudin 14 and claudin 15 on nerve degeneration and regeneration during early WD.@*RESULTS@#It was found that claudin 14/15 were upregulated in the sciatic nerve in WD. Claudin 14/15 promoted Schwann cell proliferation, migration and anti-apoptosis in vitro. PKCα, NT3, NF2, and bFGF were significantly upregulated in transfected Schwann cells. Moreover, the expression levels of the β-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK signaling pathways were also significantly altered.@*CONCLUSION@#Claudin 14/15 affect Schwann cell proliferation, migration, and anti-apoptosis via the β-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK pathways in vitro and in vivo. The results of this study may help elucidate the molecular mechanisms of the tight junction signaling pathway underlying peripheral nerve degeneration.

Low-intensity extracorporeal shock wave therapy promotes recovery of sciatic nerve injury and the role of mechanical sensitive YAP/TAZ signaling pathway for nerve regeneration / 中华医学杂志(英文版)

BACKGROUND@#Histological and functional recovery after peripheral nerve injury (PNI) is of significant clinical value as delayed surgical repair and longer distances to innervate terminal organs may account for poor outcomes. Low-intensity extracorporeal shock wave therapy (LiESWT) has already been proven to be beneficial for injured tissue recovery on various pathological conditions. The objective of this study was to explore the potential effect and mechanism of LiESWT on PNI recovery.@*METHODS@#In this project, we explored LiESWT's role using an animal model of sciatic nerve injury (SNI). Shockwave was delivered to the region of the SNI site with a special probe at 3 Hz, 500 shocks each time, and 3 times a week for 3 weeks. Rat Schwann cells (SCs) and rat perineurial fibroblasts (PNFs) cells, the two main compositional cell types in peripheral nerve tissue, were cultured in vitro, and LiESWT was applied through the cultured dish to the adherent cells. Tissues and cell cultures were harvested at corresponding time points for a reverse transcription-polymerase chain reaction, Western blotting, and immunofluorescence staining. Multiple groups were compared by using one-way analysis of variance followed by the Tukey-Kramer test for post hoc comparisons.@*RESULTS@#LiESWT treatment promoted the functional recovery of lower extremities with SNI. More nerve fibers and myelin sheath were found after LiESWT treatment associated with local upregulation of mechanical sensitive yes-associated protein (YAP)/transcriptional co-activator with a PDZ-binding domain (TAZ) signaling pathway. In vitro results showed that SCs were more sensitive to LiESWT than PNFs. LiESWT promoted SCs activation with more expression of p75 (a SCs dedifferentiation marker) and Ki67 (a SCs proliferation marker). The SCs activation process was dependent on the intact YAP/TAZ signaling pathway as knockdown of TAZ by TAZ small interfering RNA significantly attenuated this process.@*CONCLUSION@#The LiESWT mechanical signal perception and YAP/TAZ upregulation in SCs might be one of the underlying mechanisms for SCs activation and injured nerve axon regeneration.

GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus mediates nerve injury-induced neuropathic pain in rats / 生理学报

The present study was aimed to investigate the role of GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus (CSF-CN) in neuropathic pain. Intra-lateral ventricle injection of cholera toxin subunit B conjugated with horseradish peroxidase (CBHRP) was used to label the CSF-CN. Double-labeled immunofluorescent staining and Western blot were used to observe the expression of GluN2B and BDNF in the CSF-CN. Chronic constriction injury of sciatic nerve (CCI) rat model was used to duplicate the neuropathic pain. Pain behavior was scored to determine the analgesic effects of GluN2B antagonist Ro 25-6981 and BDNF neutralizing antibody on CCI rats. GluN2B and BDNF were expressed in the CSF-CN and their expression was up-regulated in CCI rats. Intra-lateral ventricle injection of GluN2B antagonist Ro 25-6981 or BDNF neutralizing antibody notably alleviated thermal hyperalgesia and mechanical allodynia in CCI rats. Moreover, the increased expression of BDNF protein in CCI rats was reversed by intra-lateral ventricle injection of Ro 25-6981. These results suggest that GluN2B and BDNF are expressed in the CSF-CN and alteration of GluN2B-BDNF pathway in the CSF-CN is involved in the modulation of the peripheral neuropathic pain.