Effect of folic acid coated-crosslinked urethane-doped polyester elastomer nerve conduit on promoting the repair of long distance peripheral nerve injury in rats / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effect of folic acid coated-crosslinked urethane-doped polyester elastomer (fCUPE) nerve conduit in repairing long distance peripheral nerve injury.@*METHODS@#Thirty-six 3-month-old male Sprague Dawley rats weighing 180-220 g were randomly assigned to 3 groups, each consisting of 12 rats: CUPE nerve conduit transplantation group (group A), fCUPE nerve conduit transplantation group (group B), and autologous nerve transplantation group (group C), the contralateral healthy limb of group C served as the control group (group D). A 20-mm-long sciatic nerve defect model was established in rats, and corresponding materials were used to repair the nerve defect according to the group. The sciatic function index (SFI) of groups A-C was calculated using the Bain formula at 1, 2, and 3 months after operation. The nerve conduction velocity (NCV) of the affected side in groups A-D was assessed using neuroelectrophysiological techniques. At 3 months after operation, the regenerated nerve tissue was collected from groups A-C for S-100 immunohistochemical staining and Schwann cell count in groups A and B to compare the level of nerve repair and regeneration in each group.@*RESULTS@#At 3 months after operation, the nerve conduits in all groups partially degraded. There was no significant adhesion between the nerve and the conduit and the surrounding tissues, the conduit was well connected with the distal and proximal nerves, and the nerve-like tissues in the conduit could be observed when the nerve conduit stents were cut off. SFI in group A was significantly higher than that in group C at each time point after operation and was significantly higher than that in group B at 2 and 3 months after operation ( P<0.05). There was no significant difference in SFI between groups B and C at each time point after operation ( P>0.05). NCV in group A was significantly slower than that in the other 3 groups at each time point after operation ( P<0.05). The NCV of groups B and C were slower than that of group D, but the difference was significant only at 1 month after operation ( P<0.05). There was no significant difference between groups B and C at each time point after operation ( P>0.05). Immunohistochemical staining showed that the nerve tissue of group A had an abnormal cavo-like structure, light tissue staining, and many non-Schwann cells. In group B, a large quantity of normal neural structures was observed, the staining was deeper than that in group A, and the distribution of dedifferentiated Schwann cells was obvious. In group C, the nerve bundles were arranged neatly, and the tissue staining was the deepest. The number of Schwann cells in group B was (727.50±57.60) cells/mm 2, which was significantly more than that in group A [(298.33±153.12) cells/mm 2] ( t=6.139, P<0.001).@*CONCLUSION@#The fCUPE nerve conduit is effective in repairing long-distance sciatic nerve defects and is comparable to autologous nerve grafts. It has the potential to be used as a substitute material for peripheral nerve defect transplantation.

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.

Inside-out and standard vein grafts associated with platelet-rich plasma (PRP) in sciatic nerve repair. A histomorphometric study

Abstract Purpose: To evaluated the tubulization technique with standard and inside-out vein, filled or not with platelet-rich plasma (PRP), in sciatic nerve repair. Methods: Seventy male Wistar rats were randomly divided into five groups: IOVNF (Inside-Out Vein with No Filling); IOVPRP (Inside-Out Vein filled with PRP); SVNF (Standard Vein with No Filling); SVPRP (Standard Vein filled with PRP); Sham (Control). The left external jugular vein was used as graft in a 10 mm nervous gap. Results: In the morphological analysis of all groups, myelinated nerve fibers with evident myelin sheath, neoformation of the epineurium and perineurium, organization of intraneural fascicles and blood vessels were observed. In the morphometry of the distal stump fibers, SVPRP group had the highest means regarding fiber diameter (3.63±0.42 μm), axon diameter (2.37±0.31 μm) and myelin sheath area (11.70±0.84 μm2). IOVPRP group had the highest means regarding axon area (4.39±1.16 μm2) and myelin sheath thickness (0.80±0.19 μm). As for values of the fiber area, IOVNF group shows highest means (15.54±0.67 μm2), but are still lower than the values of the Sham group. Conclusion: The graft filled with platelet-rich plasma, with use standard (SVPRP) or inside-out vein (IOVPRP), promoted the improvement in axonal regeneration on sciatic nerve injury.

In Vivo Effects of Adipose-Derived Stem Cells in Inducing Neuronal Regeneration in Sprague-Dawley Rats Undergoing Nerve Defect Bridged with Polycaprolactone Nanotubes

There have been many attempts for regeneration of peripheral nerve injury. In this study, we examined the in vivo effects of non-differentiated and neuronal differentiated adipose-derived stem cells (ADSCs) in inducing the neuronal regeneration in the Sprague-Dawley (SD) rats undergoing nerve defect bridged with the PCL nanotubes. Then, we performed immunohistochemical and histopathologic examinations, as well as the electromyography, in three groups: the control group (14 sciatic nerves transplanted with the PCL nanotube scaffold), the experimental group I (14 sciatic nerves with the non-differentiated ADSCs at a density of 7x105 cells/0.1 mL) and the experimental group II (14 sciatic nerves with the neuronal differentiated ADSCs at 7x105 cells/0.1 mL). Six weeks postoperatively, the degree of the neuronal induction and that of immunoreactivity to nestin, MAP-2 and GFAP was significantly higher in the experimental group I and II as compared with the control group. In addition, the nerve conduction velocity (NCV) was significantly higher in the experimental group I and II as compared with the control group (P=0.021 and P=0.020, respectively). On the other hand, there was no significant difference in the NCV between the two experimental groups (P>0.05). Thus, our results will contribute to treating patients with peripheral nerve defects using PCL nanotubes with ADSCs.

Traumatic injuries of peripheral nerves: a review with emphasis on surgical indication / Lesoes traumaticas de nervos perifericos: uma revisao com enfase na indicacao cirurgica

Traumatic peripheral nerve injury is a dramatic condition present in many of the injuries to the upper and lower extremities. An understanding of its physiopathology and selection of a suitable time for surgery are necessary for proper treatment of this challenging disorder. This article reviews the physiopathology of traumatic peripheral nerve injury, considers the most used classification, and discusses the main aspects of surgical timing and treatment of such a condition.

Traumatismos dos nervos periféricos resultam em lesões incapacitantes e estão presentes em muitas das lesões dos membros. A compreensão da fisiopatologia dessas lesões e a seleção do momento operatório mais adequado são imprescindíveis para que o tratamento seja adequado. Neste artigo revisamos a fisiopatologia das lesões traumáticas dos nervos periféricos, apresentamos a classificação mais utilizada dessas lesões e discutimos os principais aspectos relacionados ao momento da cirurgia e às formas de reparo cirúrgico.

Effect of amnion-wrapped allogenic nerve bridging on peripheral nerve injury / Efecto del puente alogénico de nervio envuelto en membrana amniótica sobre la lesión de nervio periférico

This work aims to investigate the effect of fetal amnion-wrapped acellular allogenic nerve transplantation on peripheral nerve injury (PNI) in dogs and to explore its advantages and feasibility in PNI repair. A total of 15 dogs were divided into three groups: the allogenic nerve transplantation (A), amnion-wrapped allogenic nerve transplantation (B), and allogenic nerve donor (C) groups. Neurite counts after myelin and H-E stainings, soleus muscle action potentials, and sciatic nerve conductive velocities were compared between the A and B groups at 16 w after operation. The B group showed better nerve regeneration than the A group at 16 w. Compared with the A group, the B group showed a better growth continuity of the transplanted nerve and milder inflammatory reactions around the nerve. The B group presented much more proliferated Schwannocytes and regenerated nerve fibers than the A group. The neurite density and the amplitude of the soleus muscle action potentials in the B group were significantly higher than those in the A group (P < 0.05). The two groups did not show significant differences in nerve conductive velocities (P > 0.05). Amnion-wrapped acellular allogenic nerve transplantation can improve defected nerve morphology and the quality of transplanted nerve regeneration.

El objetivo fue investigar el efecto del trasplante alogénico de nervio acelular envuelto en membrana amniótica fetal sobre la lesión del nervio periférico (LNP) en perros, y explorar sus ventajas y viabilidad en la reparación de LNP. Quince 15 perros se dividieron en tres grupos: grupo trasplante alogénico de nervio (A), grupo trasplante alogénico de nervio envuelto en membrana amniótica (B), y grupo donante alogénico de nervio (C). Se compararon el recuento de neuritas posterior a la tinción de hematoxilina-eosina (HE) y para mielina, potenciales de acción del músculo sóleo, y velocidades conductoras nerviosas del nervio ciático entre los grupos A y B, 16 semanas después de la operación. El grupo B mostró una mejor regeneración de los nervios que el grupo A a las 16 semanas. En comparación con el grupo A, el grupo B mostró una mejor continuidad del crecimiento del nervio trasplantado con reacciones inflamatorias leves alrededor del nervio. El grupo B presentó fibras nerviosas donde proliferaron más los Schwannocitos y regeneración que el grupo A. La densidad de las neuritas y la amplitud de los potenciales de acción del músculo sóleo en el grupo B fueron significativamente más altos (p <0,05). Ambos grupos no mostraron diferencias significativas en las velocidades conductoras nerviosas (P> 0,05). El trasplante alogénico de nervio acelular envuelto en membrana amniótica puede mejorar la morfología del nervio lesionado y la calidad de regeneración del nervio trasplantado.

Effects of low-level laser therapy after nerve reconstruction in rat denervated soleus muscle adaptation / Efeitos do laser de baixa potência após reconstrução nervosa na adaptação do músculo sóleo de rato

BACKGROUND: Peripheral nerve injury (PNI) rehabilitation remains a challenge for physical therapists because PNI effects are very disabling. Low-level laser therapy (LLLT) has been described as a physical resource that is able to influence enzymes called metallopeptidases (MMPs) associated with extracellular matrix (ECM) turnover, thus accelerating neuromuscular recovery after nerve crush injuries. However, the effects of LLLT in the treatment of severe nerve injuries and denervated slow-twitch muscles are still inconclusive. OBJECTIVES: The aim of this study was to evaluate the effects of different wavelengths and energy densities of LLLT irradiation, applied to a severe nerve injury after reconstruction, on denervated slow-twitch skeletal muscle adaptation. METHOD: Rats were submitted to a neurotmesis of the sciatic nerve followed by end-to-end neurorrhaphy. They received transcutaneous LLLT irradiation at the lesion site. The LLLT parameters were: wavelengths - 660 or 780 nm; energy densities - 10, 60 or 120 J/cm²; power - 40 mW; spot - 4 mm². Sciatic functional index (SFI), histological, morphometric, and zymographic analyses were performed. One-way ANOVA followed by Tukey's test was used (p<0.05). RESULTS: An atrophic pattern of muscle fibers was observed in all injured groups. The MMP activity in the soleus muscle reached normal levels. On the other hand, SFI remained below normality after PNI, indicating incapacity. No difference was found among PNI groups submitted or not to LLLT in any variable. CONCLUSIONS: LLLT applied to the nerve post-reconstruction was ineffective in delaying degenerative changes to the slow-twitch denervated muscles and in functional recovery in rats. New studies on recovery of denervated slow-twitch muscle are necessary to support clinical practice.

CONTEXTUALIZAÇÃO: A reabilitaçao das lesões nervosas periféricas (LNP) ainda é um desafio para a fisioterapia. A terapia com o laser de baixa potência (LBP) é descrita como um recurso físico capaz de interagir com enzimas relacionadas à alteração da matrix extracelular. Denominadas metalopeptidases (MMPs), essas enzimas atuam durante a recuperação neuromuscular após LNP. No entanto, os efeitos da LBP no tratamento de músculos desnervados de contração lenta após LNP graves ainda são inconclusivos. OBJETIVO: Avaliar os efeitos de diferentes comprimentos de onda e densidades de energia de irradiação de LBP, aplicado sobre o local do nervo após LNP grave e reconstrução. MÉTODO: Ratos foram submetidos a neurotmese do nervo isquiático e neurorrafia término-terminal. Os parâmetros do laser são: comprimento de onda: 660 ou 780 nm; densidades de energia: 10, 60 ou 120 J/cm²; potência: 40 mw; spot: 4 mm². O índice funcional isquiático (IFC) e análises histológicas, morfométricas e zimografia foram realizados. ANOVA one-way e teste de Tukey (p<0,05) foram utilizados. RESULTADOS: Um padrão atrófico das fibras musculares foi observado em todos os grupos com LNP. A atividade das MMPs no músculo sóleo alcançaram níveis normais. Entretanto, o IFC permaneceu inferior à normalidade após a LNP, indicando incapacidade. Não houve diferença entre os grupos de LNP submetidos ou não à LBP em qualquer variável. CONCLUSÃO: O LBP é incapaz de retardar alterações degenerativas em músculos sóleos desnervados e é ineficaz na recuperação funcional de ratos. Novos estudos sobre a recuperação do músculo de contração lenta desnervados são necessários para apoiar a prática clínica.

Lesões do plexo braquial / Brachial plexus injury

A lesão do plexo braquial acarreta grave disfunção no membro superior. Pode ser resultante de qualquer trauma com energia suficiente para tracionar, romper ou até avulsionar as raízes nervosas diretamente da coluna cervical. Os mecanismos mais comuns são os acidentes de motocicletas em homens jovens. A abordagem inclui minuciosa anamnese, com identificação do mecanismo e energia do trauma, exames eletrofisiológicos e de imagem. O tratamento especializado e precoce vai oferecer as melhores chances de recuperação. Recentemente, a contribuição da microcirurgia e as técnicas de neurotização (transferência de um nervo funcionante oriundo de uma raiz nervosa sadia e anastomosada com o coto distal do nervo lesado) têm demonstrado resultados satisfatórios. O artigo revisa a etiopatogenia das lesões de plexo braquial, o diagnóstico e as condutas atuais no tema

Brachial plexus injury causes severe upper limb dysfunction. It may result from any trauma that is strong enough to pull, break up or even avulse nerve roots directly from the cervical spine. The most common mechanisms are motorcycle accidents in young men. The approach includes thorough history taking, identifying the mechanism and energy of trauma, and electrophysiological and imaging examinations. Early specialized treatment will offer the best chances of recovery. Recently, the contribution of microsurgery and the techniques of neurotization (transfer of a functioning nerve from a healthy nervous root that is anastomosed with the distal stump of the injured nerve) have shown satisfactory results. The article reviews the etiopathogeny, diagnosis and current approaches to brachial plexus injuries

Uso da cola de fibrina na anastomose nervosa: estudo comparativo experimental em ratos / Fibrin glue use in nervous anastomosis: an experimental comparative study in rat

Há muitos anos a técnica, dita convencional, para aproximação dos cotos afastados do nervo lesado, é realizada com pontos de fios microcirúrgicos. Recentemente, a cola de fibrina tem sido utilizada para essa finalidade. O objetivo deste estudo é verificar a reinervação obtida através da sua aplicação experimental. Utilizou-se uma amostra de 35 ratos divididos em 3 grupos (grupo A: cola de fibrina; grupo B: cola e sutura; Grupo C: sutura). Após 90 dias, o nervo isquiático foi retirado e avaliado através da mensuração da espessura média da bainha de mielina das fibras regeneradas e da medição do número de axônios regenerados em um milímetro quadrado, visando a identificar o potencial de reinervação. Espessura média da bainha de mielina, em micras, foi: grupo A: 0,4417; grupo B: 0,5452; grupo C: 0,8510. O número médio de axônios reinervados por milímetro quadrado foi: grupo A: 12,95; grupo B: 25,07; grupo C: 21,17. Após a avaliação dos resultados verificou-se que o grupo que utilizou cola de fibrina apresentou menor reinervação quando comparado aos outros (AU)

For many years the so-called conventional technique to approach the separated stumps of an injured nerve has been performed using microsurgical thread stitches. Recently, fibrin glue began to be used for this purpose. The objective of this study is to look at the reinnervation achieved by using it experimentally. A sample of 35 rats was used, divided into 3 groups (Group A: Fibrin Glue; Group B: Glue and Suture; Group C: Suture). After 90 days the sciatic nerve was removed and evaluated by measuring the mean thickness of the myelin sheath of regenerated fibers and the number of axons regenerated in a square millimeter, aiming at identifying the potential for reinnervation. The mean thickness of the myelin sheath in micra was: Group A 0.4417; Group B 0.5452; Group C 0.8510. The mean number of axons reinnervated per square millimeter was: Group A 12.95; Group B 25.07; Group C 21.17. After the results were evaluated, it was found that the group using fibrin glue presented the least reinnervation as compared to the others (AU)