RESUMO
Brief low-frequency electrical stimulation (ES, 1 h, 20 Hz) of the proximal nerve stump has emerged as a potential adjunct treatment for nerve injury. Despite available experimental and clinical data, the potentials and limitations of the ES therapy still have to be defined using different animal models, types of nerves, and clinical settings. Here, we show that brief ES of the proximal stump of the transected rat femoral nerve causes, as estimated by motion analysis, enhanced functional recovery reaching preoperative levels within 5 months of injury, in contrast to the incomplete restoration in sham-stimulated (SS) animals. The functional advantage seen in ES rats was associated with higher numbers, as compared with SS, of correctly targeted quadriceps motoneurons. In contrast, ES prior to facial nerve suture did not lead to improvement of whisking compared with SS. Lack of functional effects of the treatment was correlated with lack of changes, as compared with SS, in the precision of muscle reinnervation and frequency of abnormally innervated muscle fibers. These results show that ES is an effective therapy in a spinal nerve injury model leading to complete restoration of function. Although this finding and the safety of the procedure are encouraging, the results for the facial nerve model suggest that brief ES may not be a universal treatment for nerve injuries. Anat Rec, 302:1304-1313, 2019. © 2019 Wiley Periodicals, Inc.
Assuntos
Terapia por Estimulação Elétrica/métodos , Traumatismos do Nervo Facial/patologia , Nervo Facial/fisiopatologia , Nervo Femoral/lesões , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/terapia , Recuperação de Função Fisiológica , Animais , Traumatismos do Nervo Facial/etiologia , Feminino , Ratos , Ratos Wistar , Vibrissas/fisiologiaRESUMO
Abstract Introduction: Ozone may promote moderate oxidative stress, which increases antioxidant endogenous systems. There are a number of antioxidants that have been investigated therapeutically for improving peripheral nerve regeneration. However, no previous studies have reported the effect of ozone therapy on facial nerve regeneration. Objective: We aimed to evaluate the effect of ozone therapy on facial nerve regeneration. Methods: Fourteen Wistar albino rats were randomly divided into two groups with experimental nerve crush injuries: a control group, which received saline treatment post-crush, and an experimental group, which received ozone treatment. All animals underwent surgery in which the left facial nerve was exposed and crushed. Treatment with saline or ozone began on the day of the nerve crush. Left facial nerve stimulation thresholds were measured before crush, immediately after crush, and after 30 days. After measuring nerve stimulation thresholds at 30 days post-injury, the crushed facial nerve was excised. All specimens were studied using light and electron microscopy. Results: Post-crushing, the ozone-treated group had lower stimulation thresholds than the saline group. Although this did not achieve statistical significance, it is indicative of greater functional improvement in the ozone group. Significant differences were found in vascular congestion, macrovacuolization, and myelin thickness between the ozone and control groups. Significant differences were also found in axonal degeneration and myelin ultrastructure between the two groups. Conclusion: We found that ozone therapy exerted beneficial effect on the regeneration of crushed facial nerves in rats.
Resumo Introdução: O ozônio pode promover estresse oxidativo moderado, o que aumenta sistemas endógenos antioxidantes. Há determinado número de antioxidantes sendo investigados terapeuticamente para melhorar a regeneração do nervo periférico. No entanto, nenhum estudo anterior relatou o efeito da terapia com ozônio na regeneração do nervo facial. Objetivo: Nosso objetivo foi avaliar o efeito da terapia com ozônio na regeneração do nervo facial. Método: Ao todo, 14 ratos albinos Wistar foram divididos aleatoriamente em dois grupos com lesões experimentais por esmagamento do nervo: um grupo controle, que recebeu tratamento com solução salina pós-esmagamento; e um grupo experimental, que recebeu tratamento com ozônio. Todos os animais foram submetidos a cirurgia na qual o nervo facial esquerdo foi exposto e esmagado. O tratamento com solução salina ou ozônio se iniciou no dia do esmagamento do nervo. Os limiares de estimulação do nervo facial esquerdo foram medidos antes do esmagamento, imediatamente após o esmagamento e após 30 dias. Depois de medir limiares de estimulação do nervo aos 30 dias pós-lesão, o nervo facial esmagado foi excisado. Todas as amostras foram estudadas por meio de microscopia óptica e eletrônica. Resultados: Após o esmagamento, o grupo tratado com ozônio apresentou menores limiares de estimulação do que o grupo da solução salina. Embora isso não tenha significância estatística, é indicativo de maior melhoria funcional no grupo do ozônio. Foram encontradas diferenças significativas na congestão vascular, macrovacuolização e espessura da mielina entre os grupos do ozônio e controle. Diferenças significativas também foram encontradas na degeneração axonal e ultraestrutura de mielina entre os dois grupos. Conclusão: Verificou-se que a terapia com ozônio teve efeito benéfico sobre a regeneração dos nervos faciais esmagados em ratos.
Assuntos
Animais , Ratos , Ozônio/uso terapêutico , Traumatismos do Nervo Facial/tratamento farmacológico , Regeneração Nervosa/efeitos dos fármacos , Ozônio/administração & dosagem , Ratos Wistar , Traumatismos do Nervo Facial/patologia , Modelos Animais de DoençasRESUMO
Orofacial pain is associated with peripheral and central sensitization of trigeminal nociceptive neurons. Nerve injury results in release of chemical mediators that contribute to persistent pain conditions. The activation of the transient receptor potential vanilloid 1 (TRPV1), promotes release of calcitonin gene-related peptide (CGRP) and substance P (SP) from trigeminal nerve terminals. CGRP and SP contribute to the development of peripheral hyperalgesia. The expression of SP and CGRP by primary afferent neurons is rapidly increased in response to peripheral inflammation. CGRP receptor activation promotes activation of AMPA receptors, leading to increased firing of neurons which is reflected as central sensitization. In this study we investigated whether inferior alveolar nerve (IAN) injury influences AMPA receptors, CGRP, SP and TRPV1 expression in the trigeminal ganglion (TG). The relative expression of the protein of interest from naive rats was compared to those from injured rats and animals that received low level laser therapy (LLLT). IAN-injury did not change expression of GluA1, GluA2 and CGRP, but increased the expression of TRPV1 and SP. LLLT increases GluA1 and GluA2 expression and decreases TVPV1, SP and CGRP. These results, together with previous behavioral data, suggest that IAN-injury induced changes in the proteins analyzed, which could impact on nociceptive threshold. These data may help to understand the molecular mechanisms of pain sensitization in the TG.
Assuntos
Traumatismos do Nervo Facial/radioterapia , Regulação da Expressão Gênica/efeitos da radiação , Terapia com Luz de Baixa Intensidade , Nervo Mandibular/efeitos da radiação , Gânglio Trigeminal/efeitos da radiação , Animais , Peptídeo Relacionado com Gene de Calcitonina/genética , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Traumatismos do Nervo Facial/genética , Traumatismos do Nervo Facial/metabolismo , Traumatismos do Nervo Facial/patologia , Masculino , Nervo Mandibular/metabolismo , Nervo Mandibular/patologia , Neurônios Aferentes/metabolismo , Neurônios Aferentes/patologia , Neurônios Aferentes/efeitos da radiação , Estimulação Luminosa/métodos , Ratos , Ratos Sprague-Dawley , Receptores de AMPA/genética , Receptores de AMPA/metabolismo , Transdução de Sinais , Substância P/genética , Substância P/metabolismo , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Gânglio Trigeminal/lesões , Gânglio Trigeminal/metabolismoRESUMO
INTRODUCTION: Ozone may promote moderate oxidative stress, which increases antioxidant endogenous systems. There are a number of antioxidants that have been investigated therapeutically for improving peripheral nerve regeneration. However, no previous studies have reported the effect of ozone therapy on facial nerve regeneration. OBJECTIVE: We aimed to evaluate the effect of ozone therapy on facial nerve regeneration. METHODS: Fourteen Wistar albino rats were randomly divided into two groups with experimental nerve crush injuries: a control group, which received saline treatment post-crush, and an experimental group, which received ozone treatment. All animals underwent surgery in which the left facial nerve was exposed and crushed. Treatment with saline or ozone began on the day of the nerve crush. Left facial nerve stimulation thresholds were measured before crush, immediately after crush, and after 30 days. After measuring nerve stimulation thresholds at 30 days post-injury, the crushed facial nerve was excised. All specimens were studied using light and electron microscopy. RESULTS: Post-crushing, the ozone-treated group had lower stimulation thresholds than the saline group. Although this did not achieve statistical significance, it is indicative of greater functional improvement in the ozone group. Significant differences were found in vascular congestion, macrovacuolization, and myelin thickness between the ozone and control groups. Significant differences were also found in axonal degeneration and myelin ultrastructure between the two groups. CONCLUSION: We found that ozone therapy exerted beneficial effect on the regeneration of crushed facial nerves in rats.
Assuntos
Traumatismos do Nervo Facial/tratamento farmacológico , Regeneração Nervosa/efeitos dos fármacos , Ozônio/uso terapêutico , Animais , Modelos Animais de Doenças , Traumatismos do Nervo Facial/patologia , Ozônio/administração & dosagem , Ratos , Ratos WistarRESUMO
CONCLUSION: Hyperbaric oxygen treatment (HBOT) promoted an increase of the mean axonal diameter in the group evaluated 2 weeks after lesion induction, which suggests a more advanced regeneration process. However, the number of myelin nerve fibers of the facial nerve of the rabbits was similar when compared to the control and treatment groups, in both evaluation periods. OBJECTIVE: To evaluate the effect of HBOT on the histological pattern of the facial nerve in rabbits exposed to a nerve crush injury. MATERIALS AND METHODS: Twenty rabbits were exposed to facial nerve crush injury. Ten rabbits received HBOT, 10 rabbits comprised the control group. The rabbits were sacrificed 2 and 4 weeks after the trauma. Qualitative morphological analysis, measurement of the external axonal diameters and myelin fiber count were carried out in an area of 185 000 microm2. RESULTS: There was an increase in the area of the axons and thicker myelin in the 2 weeks treatment group in comparison with the control group. The mean diameter of the axons was of 2.34 microm in the control group and of 2.81 microm in the HBOT group, with statistically significant differences. The 2 week control group had a mean number of myelin fibers of 1865.2 +/- 664, and the HBOT group had a mean number of 2026.3 +/- 302; this was not statistically significant. The 4 week control group presented a mean of 2495.1 +/- 479 fibers and the HBOT group presented a mean of 2359.9 +/- 473; this was not statistically significant.
Assuntos
Traumatismos do Nervo Facial/patologia , Traumatismos do Nervo Facial/terapia , Oxigenoterapia Hiperbárica , Regeneração Nervosa , Animais , Axônios/patologia , Axônios/fisiologia , Nervo Facial/patologia , Nervo Facial/fisiopatologia , Traumatismos do Nervo Facial/fisiopatologia , Masculino , Bainha de Mielina/patologia , Bainha de Mielina/fisiologia , Compressão Nervosa , Coelhos , Fatores de TempoRESUMO
Numerous attempts have been made to enhance and/or accelerate the recovery of injured peripheral nerves. One of the methods studied is the use of phototherapy (low power laser or light irradiation) to enhance recovery of the injured peripheral nerve. A critical analysis of the literature on the employment of phototherapy for the enhancement of the regeneration process of the rat facial and sciatic nerve (after crush injury or transection followed by surgical reconstruction) is provided, together with the description of some of the most suitable basic biological mechanisms through which laser radiation exerts its action on peripheral nerve regeneration.