Effect of herbal extracts on peripheral nerve regeneration after microsurgery of the sciatic nerve in rats.

BACKGROUND: Recent experimental studies using herbal extracts have shown the possibility of peripheral nerve regeneration. This study aimed to investigate the effects of herbal extracts on peripheral nerve regeneration in a rat sciatic nerve injury model. METHODS: A total of 53 rats were randomly assigned to a control group or one of four experimental groups. In all rats, the sciatic nerve was completely severed and microscopic epineural end-to-end neurorrhaphy was performed. Normal saline (2 mL) was topically applied to the site of nerve repair in the control group, whereas four different herbal extracts - 2 mL each of Astragalus mongholicus Bunge, Coptis japonica (Thunb.) Makino, Aconitum carmichaelii Debeaux, or Paeonia lactiflora Pall. - were topically applied to the site of nerve repair in each experimental group. Nerve conduction studies were performed at an average of 11.9 weeks after the operation, and conduction velocity and proximal and distal amplitudes were measured. Biopsies were performed at an average of 13.2 weeks after the initial neurorrhaphy. The quality of nerve anastomosis and perineural adhesion to the surrounding soft tissues was macroscopically evaluated. The neuroma size at the site of the neurorrhaphy was microscopically measured, whereas the size of the scar tissue was evaluated relative to the diameter of the repaired nerve. RESULTS: The nerve conduction study results showed the highest nerve conduction velocity in the experimental group that used the Coptis japonica (Thunb.) Makino extract and the highest proximal and distal amplitudes in the experimental group that used the Aconitum carmichaelii Debeaux extract. Macroscopic evaluations after the second operation showed that grade 2 perineural adhesion was found in 70.8% of rats. The mean neuroma size in the Coptis japonica (Thunb.) Makino, Aconitum carmichaelii Debeaux, and Paeonia lactiflora Pall. groups showed statistically significant decreases relative to the control group. The mean scar tissue formation index in the Paeonia lactiflora Pall. group showed a statistically significant decrease relative to the control group. CONCLUSIONS: The peripheral nerve regeneration effect of the herbal extracts was confirmed through decreased neuroma and scar tissue formation.

SURGICAL TREATMENT OF PERIPHERAL NERVES COMBAT WOUNDS OF THE EXTREMITIES.

OBJECTIVE: The aim: Improving the effectiveness of patients' treatment with combat injuries of the peripheral nervous system, which consists in the application and development of new methods of reconstructive interventions, optimizing a set of therapeutic and diagnostic measures for the most effective management of this category of patients with peripheral nerve injury. PATIENTS AND METHODS: Materials and methods: The research is based on the results of surgical treatment of 138 patients with combat injuries of peripheral nerves for the period from 2014 to 2020. The mean age was 33.5 ± 2.1 years. Patients were treated for 1 to 11 months after injury (median - 8 months). Damage to the sciatic nerve was observed in 26.1%, ulnar - in 20.3%, median - in 18.8%, radial - in 15.9%, tibial - in 10.9%, common peroneal nerve - in 8% of cases. RESULTS: Results: It was shown that in all patients was significantly improved the recovery of all nerves. In the period from 9 to 12 months, the degree of recovery of motor function to M0-M2 was observed in 40.6%, to M3 - in 35.5%, to M4 - in 16.7%, to M5 - in 7,2%. The degree of recovery of sensitivity to S0-S2 was observed in 36.2%, to S3 - in 42.8%, to S4 - in 17.4%, to S5 - in 3.6%. Regression of pain syndrome after surgery was observed in 81.2% of patients. CONCLUSION: Conclusions: The results of surgical treatment of peripheral nerves gunshot injury are generally worse than other types of nerve injuries. The best results of surgical treatment of combat trauma of peripheral nerves are obtained in patients with sciatic nerve damage.

New bioresorbable wraps based on oxidized polyvinyl alcohol and leukocyte-fibrin-platelet membrane to support peripheral nerve neurorrhaphy: preclinical comparison versus NeuraWrap.

Nerve wrapping improves neurorrhaphy outcomes in case of peripheral nerve injuries (PNIs). The aim of this preclinical study was to assess the efficacy of two novel biodegradable wraps made of a synthetic 1% oxidized polyvinyl alcohol (OxPVA) and a natural leukocyte-fibrin-platelet membrane (LFPm) versus the commercial product NeuraWrap. After rats sciatic nerve transection and neurorrhaphy, the wraps were implanted and compared for functional outcome, by sciatic function index assessment; structural characteristics, by histological/immunohistochemical analysis; ultrastructural features, by transmission electron microscopy. Moreover, a morphometric study was also performed and collagen distribution was observed by Second Harmonic Generation microscopy. After 12 weeks from implantation, all wraps assured nerve function recovery; no scar tissue/neuromas were visible at dissection. LFPm wraps were completely resorbed, while residues of OxPVA and NeuraWrap were observed. In all groups, biocompatibility was confirmed by the absence of significant inflammatory infiltrate. According to histological/immunohistochemical analysis and morphometric findings, OxPVA and LFPm wraps were both effective in preserving nerve integrity. These results assess that bioengineered OxPVA and LFPm wraps successfully guarantee favorable lesion recovery after PNI/neurorrhaphy and, in future, may be considered an interesting alternative to the commercial NeuraWrap.

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.

The effect of different application timings of hyperbaric oxygen treatment on nerve regeneration in rats.

BACKGROUND: The aim of the study was to determine the effect of different application timings of hyperbaric oxygen treatment (HBO) on nerve regeneration in rats. MATERIALS AND METHODS: A total of forty 12-week-old female Wistar albino rats were used. The sciatic nerve was transected. The nerve ends were then realigned and repaired using standard microsurgical techniques. Animals were randomly assigned to four groups: 1) No hyperbaric oxygen, sectioned and repaired; 2) HBO started at postoperative first hour, sectioned and repaired; 3) HBO started at postoperative first week, sectioned, and repaired; and 4) HBO started at postoperative second week, sectioned, and repaired. All rats in all groups were evaluated with gait analysis at 8 and 16 weeks postoperatively. Sciatic function index was calculated. Sciatic nerve samples were taken after gait analysis at 16th week. Foreign body reaction, the intensity of the inflammatory cells and types, repair-associated vascular proliferation in the field, axonal vacuolar degeneration of the fibers from the cut line transition density and switching layout, and myelinization density with perineural sheath were evaluated histopathologically. RESULTS: At the 16th week, group 2 demonstrated the best gait analysis results. Gait analysis was better for group 3 than groups 1 and 4 (P < 0.05). No significant differences were observed among the groups in inflammation (P > 0.05). Fibrosis was statistically less in group 2 than that in other groups (P < 0.05); however, no significant differences were observed among groups 1, 3, and 4 (P > 0.05). CONCLUSIONS: Our results suggest that initiating HBO early after nerve repair will make a positive impact on recovery. © 2016 Wiley Periodicals, Inc. Microsurgery 36:586-592, 2016.

Adjuvant neurotrophic factors in peripheral nerve repair with chondroitin sulfate proteoglycan-reduced acellular nerve allografts.

BACKGROUND: Acellular nerve allografts are now standard tools in peripheral nerve repair because of decreased donor site morbidity and operative time savings. Preparation of nerve allografts involves several steps of decellularization and modification of extracellular matrix to remove chondroitin sulfate proteoglycans (CSPGs), which have been shown to inhibit neurite outgrowth through a poorly understood mechanism involving RhoA and extracellular matrix-integrin interactions. Chondroitinase ABC (ChABC) is an enzyme that degrades CSPG molecules and has been shown to promote neurite outgrowth after injury of the central and peripheral nervous systems. Variable results after ChABC treatment make it difficult to predict the effects of this drug in human nerve allografts, especially in the presence of native extracellular signaling molecules. Several studies have shown cross-talk between neurotrophic factor and CSPG signaling pathways, but their interaction remains poorly understood. In this study, we examined the adjuvant effects of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) on neurite outgrowth postinjury in CSPG-reduced substrates and acellular nerve allografts. MATERIALS AND METHODS: E12 chicken DRG explants were cultured in medium containing ChABC, ChABC + NGF, ChABC + GDNF, or control media. Explants were imaged at 3 d and neurite outgrowths measured. The rat sciatic nerve injury model involved a 1-cm sciatic nerve gap that was microsurgically repaired with ChABC-pretreated acellular nerve allografts. Before implantation, nerve allografts were incubated in NGF, GDNF, or sterile water. Nerve histology was evaluated at 5 d and 8 wk postinjury. RESULTS: The addition of GDNF in vitro produced significant increase in sensory neurite length at 3 d compared with ChABC alone (P < 0.01), whereas NGF was not significantly different from control. In vivo adjuvant NGF produced increases in total myelinated axon count (P < 0.005) and motor axon count (P < 0.01), whereas significantly reducing IB4+ nociceptor axon count (P < 0.01). There were no significant differences produced by in vivo adjuvant GDNF. CONCLUSIONS: This study provides initial evidence that CSPG-reduced nerve grafts may disinhibit the prosurvival effects of NGF in vivo, promoting motor axon outgrowth and reducing regeneration of specific nociceptive neurons. Our results support further investigation of adjuvant NGF therapy in CSPG-reduced acellular nerve grafts.

Evidence and techniques in rehabilitation following nerve injuries.

Following upper extremity peripheral nerve injury and surgery, rehabilitation is essential to optimize sensorimotor function and outcome. This review presents the evidence and related literature regarding a few key topics related to rehabilitation following peripheral nerve injury and surgery.

Serious axillary nerve injury caused by subscapular artery compression resulting from use of backpacks.

A palsy of the brachial plexus elements caused by carrying a heavy backpack is a very rare injury usually occurring in soldiers or hikers, and recovery is usually spontaneous. We describe here the case of male civilian presenting with an isolated serious axillary nerve palsy associated with chronic backpack use. During the surgery, a dumbbell-shaped neuroma-in-continuity was found which was caused by direct pressure from the subscapular artery. After resection of the neuroma, a nerve graft from the sural nerve was used to reconstruct the nerve. Reinnervation was successful and the patient was able to abduct his arm to its full range, with full muscle strength, within 24 months.

New synthetic prosthesis for peripheral nerve injuries: an experimental pilot study.

INTRODUCTION: Even the most modern technology has failed to induce satisfactory functional regeneration of traumatically severed peripheral nerves. Delayed neural regeneration and in consequence, slower neural conduction seriously limit muscle function in the area supplied by the injured nerve. This study aimed to compare a new nerve coaptation system involving an innovative prosthesis with the classical clinical method of sutured nerve coaptation. Besides the time and degree of nerve regeneration, the influence of electrostimulation was also tested. METHODS: The sciatic nerve was severed in 14 female Göttingen minipigs with an average weight of 40.4 kg. The animals were randomized into 2 groups: One group received the new prosthesis and the other underwent microsurgical coaptation. In each group, according to the randomization a part of the animals received postoperative electrostimulation. Postoperative monitoring and the stimulation schedule covered a period of 9 months, during which axonal budding was evaluated monthly. RESULTS: The data from the pilot study indicate that results with the nerve prosthesis were comparable with those of conventional coaptation. CONCLUSION: The results indicate that implantation of the nerve prosthesis allows for good and effective neural regeneration. This new and simple treatment option for peripheral nerve injuries can be performed in any hospital with surgical facilities as it does not involve the demanding microsurgical suture technique that can only be performed in specialized centers.

Applications of biomaterials in plastic surgery.

The expansion of the application of biomaterials in plastic surgery has led to the increased availability of commercial products in recent years. This overview discusses soft tissue fillers, bioengineered skins, acellular dermal matrices, biomaterials for craniofacial surgery, and peripheral nerve repair. We summarize indications, properties, uses, types, advantages and disadvantages of some of the currently available products from each category. Finally, the current state of development in drug delivery system is also briefly summarized.

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.

Effects of low-level laser therapy after nerve reconstruction in rat denervated soleus muscle adaptation.

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.