RESUMEN
Axonotmesis causes sensorimotor and neurofunctional deficits, and its regeneration can occur slowly or not occur if not treated appropriately. Low-level laser therapy (LLLT) promotes nerve regeneration with the proliferation of myelinating Schwann cells to recover the myelin sheath and the production of glycoproteins for endoneurium reconstruction. This study aimed to evaluate the effects of LLLT on sciatic nerve regeneration after compression injury by means of the sciatic functional index (SFI) and Raman spectroscopy (RS). For this, 64 Wistar rats were divided into two groups according to the length of treatment: 14 days (n = 32) and 21 days (n = 32). These two groups were subdivided into four sub-groups of eight animals each (control 1; control 2; laser 660 nm; laser 808 nm). All animals had surgical exposure to the sciatic nerve, and only control 1 did not suffer nerve damage. To cause the lesion in the sciatic nerve, compression was applied with a Kelly clamp for 6 s. The evaluation of sensory deficit was performed by the painful exteroceptive sensitivity (PES) and neuromotor tests by the SFI. Laser 660 nm and laser 808 nm sub-groups were irradiated daily (100 mW, 40 s, energy density of 133 J/cm2). The sciatic nerve segment was removed for RS analysis. The animals showed accentuated sensory and neurofunctional deficit after injury and their rehabilitation occurred more effectively in the sub-groups treated with 660 nm laser. Control 2 sub-group did not obtain functional recovery of gait. The RS identified sphingolipids (718, 1065, and 1440 cm-1) and collagen (700, 852, 1004, 1270, and 1660 cm-1) as biomolecular characteristics of sciatic nerves. Principal component analysis revealed important differences among sub-groups and a directly proportional correlation with SFI, mainly in the sub-group laser 660 nm treated for 21 days. In the axonotmesis-type lesion model presented herein, the 660 nm laser was more efficient in neurofunctional recovery, and the Raman spectra of lipid and protein properties were attributed to the basic biochemical composition of the sciatic nerve.
Asunto(s)
Lesiones por Aplastamiento , Terapia por Luz de Baja Intensidad , Traumatismos de los Nervios Periféricos , Neuropatía Ciática , Animales , Lesiones por Aplastamiento/radioterapia , Terapia por Luz de Baja Intensidad/métodos , Compresión Nerviosa , Regeneración Nerviosa/fisiología , Traumatismos de los Nervios Periféricos/radioterapia , Ratas , Ratas Wistar , Nervio Ciático/lesiones , Neuropatía Ciática/patología , Espectrometría RamanRESUMEN
OBJECTIVES: Whole-body vibration (WBV) is commonly used to improve motor function, balance and functional performance, but its effects on the body are not fully understood. The main objective was to evaluate the morphometric and functional effects of WBV in an experimental nerve regeneration model. METHODS: Wistar rats were submitted to unilateral sciatic nerve crush and treated with WBV (4-5 weeks), started at 3 or 10 days after injury. Functional performances were weekly assessed by sciatic functional index, horizontal ladder rung walking and narrow beam tests. Nerve histomorphometry analysis was assessed at the end of the protocol. RESULTS: Injured groups, sedentary and WBV started at 3 days, had similar functional deficits. WBV, regardless of the start time, did not alter the histomorphometry parameters in the regeneration process. CONCLUSIONS: The earlier therapy did not change the expected and natural recovery after the nerve lesion, but when the WBV starts later it seems to impair function parameter of recovery.
Asunto(s)
Regeneración Nerviosa/fisiología , Nervios Periféricos/fisiología , Recuperación de la Función/fisiología , Neuropatía Ciática/terapia , Vibración/uso terapéutico , Animales , Masculino , Ratas , Ratas Wistar , Neuropatía Ciática/patología , Neuropatía Ciática/fisiopatologíaRESUMEN
Mice cohabiting with a conspecific in chronic pain display anxiogenesis in the elevated plus-maze (EPM). Given that the anterior cingulate (ACC) and insular (InC) cortices play a role in the modulation of anxiety, pain, and emotional contagion, we investigated (a) the FosB activation in both brain areas and (b) the effects of intra-ACC or -InC injection of cobalt chloride (CoCl2, a synaptic blocker), on the anxiety of mice cohabiting with a cagemate suffering pain. Twenty-one days after birth, male Swiss mice were housed in pairs for 14 days to establish familiarity. On the 14th day, mice were divided into two groups: cagemate sciatic nerve constriction (CNC; i.e., one animal of each pair was subjected to sciatic nerve constriction), and cagemate sham (CS; i.e., a similar procedure but without suffering nerve constriction). After that, both groups were housed again with the same pairs for the other 14 days. On the 28th day, mice had their brains removed for the immunoassays analyses (Exp. 1). For experiments 2 and 3, on the 23rd day, the cagemates received guide cannula implantation bilaterally in the ACC or InC and, on the 28th day, they received local injections of saline or CoCl2, and then were exposed to the EPM. Results showed that cohabitation with a conspecific with chronic pain decreases and increases neuronal activation (FosB) within the ACC and InC, respectively. Intra-ACC or InC injection of CoCl2 reversed the anxiogenic effect in those animals that cohabited with a conspecific in chronic pain. ACC and InC seem to modulate anxiety induced by emotional contagion in animals cohabitating with a conspecific suffering pain.
Asunto(s)
Ansiedad/metabolismo , Dolor Crónico/metabolismo , Empatía/fisiología , Giro del Cíngulo/metabolismo , Corteza Insular/metabolismo , Interacción Social , Animales , Ansiedad/patología , Ansiedad/psicología , Dolor Crónico/patología , Dolor Crónico/psicología , Giro del Cíngulo/patología , Corteza Insular/patología , Masculino , Aprendizaje por Laberinto/fisiología , Ratones , Neuropatía Ciática/patología , Neuropatía Ciática/psicologíaRESUMEN
OBJECTIVE: To evaluate the effects of right sciatic nerve compression and cryotherapy on muscle tissue. METHODS: We used 42 male Wistar rats, subdivided in the following Groups Control, Injury 3, Injury 8 and Injury 15 submitted to nerve compression and euthanized in the 3rd, 8th and 15th day after surgery. The Cryotherapy Injury 3 was entailed treatment with cryotherapy by immersion of the animal in recipient for 20 minutes during 1 day, then animals were euthanized at the 3rd day after surgery, and the Cryotherapy Injury 8 and the Cryotherapy Injury 15 was treated for 6 days, and euthanized at the 8th and 15th day after surgery. Functional evaluation was performed by the grasping strength of the right pelvic limb. The right tibialis anterior muscles were evaluated for mass, smaller diameter and cross-sectional area. In the Cryotherapy Injury 8 and the Cryotherapy Injury 15 groups, the hydroxyproline was dosed in the right soles. RESULTS: In the compression there was a significant difference in the Injury Groups compared with the Control Group (p<0.05). In the smaller diameter, the compression in Control Group was higher than Injury 8 (p=0.0094), Injury 15 (p=0.002) and Cryotherapy Injury 15 (p<0.001) groups. The comparison between groups with euthanasia in the same post-operative period, a significant difference (p=0.0363) was seen in day 8th after surgery, and this result in Cryotherapy Injury Group was greater than Injury Group. In the fiber area, Control Group was also higher than the Injury 8 (p=0.0018), the Injury 15 (p<0.001) and the Cryotherapy Injury 15 (p<0.001). In hydroxyproline, no significant difference was seen between groups. CONCLUSION: Nerve damage resulted in decreased muscle strength and trophism, the cryotherapy delayed hypotrophy, but this effect did not persist after cessation of treatment.
Asunto(s)
Crioterapia/métodos , Síndromes de Compresión Nerviosa/patología , Síndromes de Compresión Nerviosa/terapia , Nervio Ciático/patología , Neuropatía Ciática/patología , Neuropatía Ciática/terapia , Animales , Modelos Animales de Enfermedad , Hipertrofia/fisiopatología , Masculino , Debilidad Muscular/fisiopatología , Síndromes de Compresión Nerviosa/fisiopatología , Distribución Aleatoria , Ratas Wistar , Valores de Referencia , Reproducibilidad de los Resultados , Nervio Ciático/fisiopatología , Nervio Ciático/cirugía , Neuropatía Ciática/fisiopatología , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: This study aims to investigate morphological alterations caused by partial sciatic nerve ligation (PNL) and the efficacy of a moderate-intensity swimming training as therapeutic strategy for nerve regeneration. METHODS: A number of 30 male adult mice were equally divided in control, 14 days after PNL (PNL 14 days), 42 days after PNL (PNL 42 days), 70 days after PNL (PNL 70 days) and 5-week exercise training after 7 days post-lesion (PNL trained 35 days) groups. PNL trained 35 days group began with a 10-min session for 3 days and this time was gradually increased by 10 min every three sessions until the animals had swum for 50 min per session. Morphoquantitative analysis was carried out to assess nerve regeneration in each group. RESULTS: PNL 14 days group exhibited less degenerating signs than PNL 42 days group, where most post-lesion alterations were visualized. Nerve area and minimum diameter were significantly lower (p < 0.05) than control group. PNL 70 days group showed a greater degree of regenerating fibers and similar morphometric parameters to control group. PNL trained 35 days demonstrated signs of regeneration, reaching control group values in the morphometric analysis. DISCUSSION: PNL promotes great histopathological changes, which became more visible at 42 post-injury days. A natural nerve-regeneration tendency was observed throughout time, as observed in PNL 70 days group; nevertheless, moderate swimming training was found to be a therapeutic resource for nerve regeneration, accelerating such process from a morphoquantitative perspective. ABBREVIATIONS: ANOVA: One-way analysis of variance; BDNF: Brain-derived neurotrophic factor; FGF-2: Fibroblast growth factor 2; GDNF: Glial cell line derived neurotrophic factor; IGF: Insulin-link growth factor; IL-1ß: Interleukin-1ß; NGF: Neural growth factor; PBS: Phosphate-buffered saline; PNL: Partial sciatic nerve ligation.
Asunto(s)
Terapia por Ejercicio , Regeneración Nerviosa , Neuropatía Ciática/patología , Neuropatía Ciática/terapia , Natación , Animales , Modelos Animales de Enfermedad , Masculino , Ratones Endogámicos BALB C , Síndromes de Compresión Nerviosa/patología , Síndromes de Compresión Nerviosa/terapia , Degeneración Nerviosa/patología , Degeneración Nerviosa/terapia , Neuralgia/patología , Neuralgia/terapia , Distribución Aleatoria , Nervio Ciático/patologíaRESUMEN
The present study compares the effects of a low and high doses of simvastatin in a model of peripheral neuropathy by evaluating sensorial, motor, and morphological parameters. First, male Wistar rats were orally treated with vehicle (saline, 1 mL/kg), simvastatin (2 and 80 mg/kg) or morphine (2 mg/kg, s.c.), 1 h before 2.5% formalin injection. Neuropathic pain was induced by crushing the sciatic nerve, and mechanical and cold allodynia, nerve function, histology, MPO and NAG concentrations, as well as mevalonate induced-nociception were evaluated. Animals were orally treated with vehicle, simvastatin, or gabapentin (30 mg/kg) for 18 days. Simvastatin (2 and 80 mg/kg) reduced the inflammatory pain induced by formalin, but failed to decrease the paw edema. Mechanical allodynia was reduced by the simvastatin (2 mg/kg) until the 12th day after injury and until the 18th day by gabapentin. However, both simvastatin and gabapentin treatments failed in attenuated cold allodynia or improved motor function. Interestingly, both doses of simvastatin showed a neuroprotective effect and inhibited MPO activity without altering kidney and hepatic parameters. Additionally, only the higher dose of simvastatin reduced the cholesterol levels and the nociception induced by mevalonate. Our results reinforce the antinociceptive, antiallodynic, and anti-inflammatory effects of oral simvastatin administration, which can strongly contribute to the sciatic nerve morphology preservation. Furthermore, our data suggest that lower and higher doses of simvastatin present beneficial effects that are dependent and independent of the mevalonate pathway, respectively, without causing signs of nerve damage.
Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hiperalgesia/tratamiento farmacológico , Neuralgia/tratamiento farmacológico , Dimensión del Dolor/efectos de los fármacos , Neuropatía Ciática/tratamiento farmacológico , Simvastatina/uso terapéutico , Animales , Frío/efectos adversos , Relación Dosis-Respuesta a Droga , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Hiperalgesia/metabolismo , Hiperalgesia/patología , Masculino , Neuralgia/metabolismo , Neuralgia/patología , Dimensión del Dolor/métodos , Peroxidasa/antagonistas & inhibidores , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Neuropatía Ciática/metabolismo , Neuropatía Ciática/patología , Simvastatina/farmacología , Resultado del TratamientoRESUMEN
Peripheral nerve injury (PNI) activates the immune system, resulting in increased proinflammatory cytokines at the site of injury and in the spinal cord dorsal horn. Exercise modulates the immune system promoting an anti-inflammatory phenotype of macrophages in uninjured muscle, and increases in anti-inflammatory cytokines can promote healing and analgesia. We proposed that PNI will decrease, and treadmill exercise will increase, release of anti-inflammatory cytokines at the site of injury and in the spinal cord. We show that 2 weeks of treadmill exercise improves neuropathic pain behaviors in mice: mechanical hyperalgesia, escape and avoidance behavior, and spontaneous locomotor activity. Peripheral nerve injury reduced anti-inflammatory cytokines (interleukin-4 [IL-4], IL-1ra, and IL-5) at the site of nerve injury and in the spinal dorsal horn, whereas exercise restored IL-4, IL-1ra, and IL-5 concentrations to preinjury levels. IL4 mice and mice treated with IL-4 antibody did not develop analgesia to treadmill exercise. Using immunohistochemical staining of the sciatic nerve, treadmill exercise increased the percentage of M2 macrophages (secretes anti-inflammatory cytokines) and decreased M1 macrophages (secretes proinflammatory cytokines) when compared with sedentary mice. The increased M2 and decreased M1 macrophages in exercised mice did not occur in IL-4 mice. In the spinal cord, PNI increased glial cell activation, brain-derived neurotrophic factor and ß-nerve growth factor levels, and decreased IL-4 and IL-1ra levels, whereas treadmill exercise suppressed glial cells activation (Glial Fibrillary Acidic Protein and Iba1 immunoreactivity), reduced brain-derived neurotrophic factor and ß-nerve growth factor, and increased IL-4, IL-1ra, and IL-5 concentrations. Our results suggest that IL-4 mediates the analgesia produced by low-intensity exercise by modulating peripheral and central neuroimmune responses in mice with neuropathic pain.
Asunto(s)
Interleucina-4/metabolismo , Condicionamiento Físico Animal/métodos , Neuropatía Ciática/patología , Neuropatía Ciática/rehabilitación , Médula Espinal/metabolismo , Animales , Anticuerpos/uso terapéutico , Reacción de Prevención/fisiología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Prueba de Esfuerzo , Conducta Exploratoria/fisiología , Regulación de la Expresión Génica/fisiología , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/etiología , Interleucina-4/genética , Interleucina-4/inmunología , Masculino , Ratones , Ratones Noqueados , Factor de Crecimiento Nervioso/metabolismo , Neuroglía/efectos de los fármacos , Neuroglía/metabolismo , Umbral del Dolor/fisiología , Neuropatía Ciática/tratamiento farmacológico , Neuropatía Ciática/fisiopatología , Médula Espinal/efectos de los fármacos , Médula Espinal/patología , Factores de TiempoRESUMEN
ABSTRACT Objective: To evaluate the effects of right sciatic nerve compression and cryotherapy on muscle tissue. Methods: We used 42 male Wistar rats, subdivided in the following Groups Control, Injury 3, Injury 8 and Injury 15 submitted to nerve compression and euthanized in the 3rd, 8th and 15th day after surgery. The Cryotherapy Injury 3 was entailed treatment with cryotherapy by immersion of the animal in recipient for 20 minutes during 1 day, then animals were euthanized at the 3rd day after surgery, and the Cryotherapy Injury 8 and the Cryotherapy Injury 15 was treated for 6 days, and euthanized at the 8th and 15th day after surgery. Functional evaluation was performed by the grasping strength of the right pelvic limb. The right tibialis anterior muscles were evaluated for mass, smaller diameter and cross-sectional area. In the Cryotherapy Injury 8 and the Cryotherapy Injury 15 groups, the hydroxyproline was dosed in the right soles. Results: In the compression there was a significant difference in the Injury Groups compared with the Control Group (p<0.05). In the smaller diameter, the compression in Control Group was higher than Injury 8 (p=0.0094), Injury 15 (p=0.002) and Cryotherapy Injury 15 (p<0.001) groups. The comparison between groups with euthanasia in the same post-operative period, a significant difference (p=0.0363) was seen in day 8th after surgery, and this result in Cryotherapy Injury Group was greater than Injury Group. In the fiber area, Control Group was also higher than the Injury 8 (p=0.0018), the Injury 15 (p<0.001) and the Cryotherapy Injury 15 (p<0.001). In hydroxyproline, no significant difference was seen between groups. Conclusion: Nerve damage resulted in decreased muscle strength and trophism, the cryotherapy delayed hypotrophy, but this effect did not persist after cessation of treatment.
RESUMO Objetivo: Avaliar os efeitos da compressão nervosa do isquiático direito e da crioterapia no tecido muscular. Métodos: Foram utilizados 42 ratos Wistar machos, subdivididos nos Grupos Controle, Lesão 3, Lesão 8 e Lesão 15, submetidos a compressão nervosa e eutanasiados, respectivamente, no 3°, 8° e 15° dias pós-operatório; Lesão Crioterapia 3, tratado com crioterapia, por imersão durante 20 minutos, por 1 dia, e eutanasiados no 3° dia pós-operatório; e Lesão Crioterapia 8 e Lesão Crioterapia 15, tratados durante 6 dias e eutanasiados no 8° e 15° dias pós-operatório. A avaliação funcional foi realizada pela força de preensão do membro pélvico direito. Os músculos tibiais anteriores direitos foram avaliados quanto a massa, menor diâmetro e área de secção transversa. Em Lesão Crioterapia 8 e Lesão Crioterapia 15, foi dosada a hidroxiprolina nos sóleos direitos. Resultados: Na preensão, houve diferença significativa nos Grupos Lesão quando comparados ao Grupo Controle (p<0,05). No menor diâmetro, o Grupo Controle foi maior que Lesão 8 (p=0,0094), Lesão 15 (p = 0,002) e Lesão Crioterapia 15 (p<0,001). Na comparação entre os grupos com eutanásia no mesmo pós-operatório, houve diferença significativa (p=0,0363) no 8° pós-operatório, sendo Lesão Crioterapia maior que Lesão. Na área das fibras, o Grupo Controle também foi maior que Lesão 8 (p=0,0018), Lesão 15 (p<0,001) e Lesão Crioterapia 15 (p<0,001). Na hidroxiprolina, não houve diferença significativa entre os grupos. Conclusão: A lesão nervosa resultou na diminuição da força e em trofismo muscular, e a crioterapia retardou a hipotrofia, porém este efeito não se manteve após o tratamento cessar.
Asunto(s)
Animales , Masculino , Nervio Ciático/patología , Crioterapia/métodos , Neuropatía Ciática/patología , Neuropatía Ciática/terapia , Síndromes de Compresión Nerviosa/patología , Síndromes de Compresión Nerviosa/terapia , Valores de Referencia , Nervio Ciático/cirugía , Nervio Ciático/fisiopatología , Factores de Tiempo , Distribución Aleatoria , Reproducibilidad de los Resultados , Resultado del Tratamiento , Ratas Wistar , Debilidad Muscular/fisiopatología , Neuropatía Ciática/fisiopatología , Modelos Animales de Enfermedad , Hipertrofia/fisiopatología , Síndromes de Compresión Nerviosa/fisiopatologíaRESUMEN
OBJECTIVE: To evaluate the action of vanillin (Vanilla planifolia) on the morphology of tibialis anterior and soleus muscles after peripheral nerve injury. METHODS: Wistar rats were divided into four groups, with seven animals each: Control Group, Vanillin Group, Injury Group, and Injury + Vanillin Group. The Injury Group and the Injury + Vanillin Group animals were submitted to nerve injury by compression of the sciatic nerve; the Vanillin Group and Injury + Vanillin Group, were treated daily with oral doses of vanillin (150mg/kg) from the 3rd to the 21st day after induction of nerve injury. At the end of the experiment, the tibialis anterior and soleus muscles were dissected and processed for light microscopy and submitted to morphological analysis. RESULTS: The nerve compression promoted morphological changes, typical of denervation, and the treatment with vanillin was responsible for different responses in the studied muscles. For the tibialis anterior, there was an increase in the number of satellite cells, central nuclei and fiber atrophy, as well as fascicular disorganization. In the soleus, only increased vascularization was observed, with no exacerbation of the morphological alterations in the fibers. CONCLUSION: The treatment with vanillin promoted increase in intramuscular vascularization for the muscles studied, with pro-inflammatory potential for tibialis anterior, but not for soleus muscle. OBJETIVO: Avaliar a ação da vanilina (Vanilla planifolia) sobre a morfologia dos músculos tibial anterior e sóleo após lesão nervosa periférica. MÉTODOS: Ratos Wistar foram divididos em quatro grupos, com sete animais cada, sendo Grupo Controle, Grupo Vanilina, Grupo Lesão e Grupo Lesão + Vanilina. Os animais dos Grupos Lesão e Grupo Lesão + Vanilina foram submetidos à lesão nervosa por meio da compressão do nervo isquiático, e os Grupos Vanilina e Grupo Lesão + Vanilina foram tratados diariamente com doses orais de vanilina (150mg/kg) do 3o ao 21o dia após a indução da lesão nervosa. Ao término do experimento, os músculos tibial anterior e sóleo foram dissecados e seguiram o processamento de rotina em microscopia de luz, para posterior análise morfológica. RESULTADOS: A compressão nervosa promoveu alterações morfológicas características de denervação, sendo que o tratamento com vanilina foi responsável por respostas distintas nos músculos estudados. Para o tibial anterior, houve aumento do número de células satélites, núcleos centrais e atrofia das fibras, bem como desorganização fascicular. Já no sóleo, houve apenas aumento da vascularização, sem exacerbação das alterações morfológicas nas fibras. CONCLUSÃO: O tratamento com vanilina promoveu o aumento da vascularização intramuscular para os músculos estudados, com potencial pró-inflamatório para o tibial anterior, o que não ocorreu no músculo sóleo.
Asunto(s)
Antiinflamatorios/farmacología , Benzaldehídos/farmacología , Tejido Conectivo/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Neuropatía Ciática/patología , Animales , Tejido Conectivo/patología , Humanos , Masculino , Modelos Animales , Fibras Musculares Esqueléticas/efectos de los fármacos , Músculo Esquelético/patología , Distribución Aleatoria , Ratas Wistar , Neuropatía Ciática/rehabilitaciónAsunto(s)
Neurilemoma/diagnóstico , Neoplasias del Sistema Nervioso Periférico/diagnóstico , Neuropatía Ciática/diagnóstico , Ciática/diagnóstico , Adulto , Nalgas/inervación , Diagnóstico Diferencial , Femenino , Humanos , Neurilemoma/patología , Neoplasias del Sistema Nervioso Periférico/patología , Nervio Ciático/patología , Neuropatía Ciática/patologíaRESUMEN
ABSTRACT Objective To evaluate the action of vanillin (Vanilla planifolia) on the morphology of tibialis anterior and soleus muscles after peripheral nerve injury. Methods Wistar rats were divided into four groups, with seven animals each: Control Group, Vanillin Group, Injury Group, and Injury + Vanillin Group. The Injury Group and the Injury + Vanillin Group animals were submitted to nerve injury by compression of the sciatic nerve; the Vanillin Group and Injury + Vanillin Group, were treated daily with oral doses of vanillin (150mg/kg) from the 3rd to the 21st day after induction of nerve injury. At the end of the experiment, the tibialis anterior and soleus muscles were dissected and processed for light microscopy and submitted to morphological analysis. Results The nerve compression promoted morphological changes, typical of denervation, and the treatment with vanillin was responsible for different responses in the studied muscles. For the tibialis anterior, there was an increase in the number of satellite cells, central nuclei and fiber atrophy, as well as fascicular disorganization. In the soleus, only increased vascularization was observed, with no exacerbation of the morphological alterations in the fibers. Conclusion The treatment with vanillin promoted increase in intramuscular vascularization for the muscles studied, with pro-inflammatory potential for tibialis anterior, but not for soleus muscle.
RESUMO Objetivo Avaliar a ação da vanilina (Vanilla planifolia) sobre a morfologia dos músculos tibial anterior e sóleo após lesão nervosa periférica. Métodos Ratos Wistar foram divididos em quatro grupos, com sete animais cada, sendo Grupo Controle, Grupo Vanilina, Grupo Lesão e Grupo Lesão + Vanilina. Os animais dos Grupos Lesão e Grupo Lesão + Vanilina foram submetidos à lesão nervosa por meio da compressão do nervo isquiático, e os Grupos Vanilina e Grupo Lesão + Vanilina foram tratados diariamente com doses orais de vanilina (150mg/kg) do 3o ao 21o dia após a indução da lesão nervosa. Ao término do experimento, os músculos tibial anterior e sóleo foram dissecados e seguiram o processamento de rotina em microscopia de luz, para posterior análise morfológica. Resultados A compressão nervosa promoveu alterações morfológicas características de denervação, sendo que o tratamento com vanilina foi responsável por respostas distintas nos músculos estudados. Para o tibial anterior, houve aumento do número de células satélites, núcleos centrais e atrofia das fibras, bem como desorganização fascicular. Já no sóleo, houve apenas aumento da vascularização, sem exacerbação das alterações morfológicas nas fibras. Conclusão O tratamento com vanilina promoveu o aumento da vascularização intramuscular para os músculos estudados, com potencial pró-inflamatório para o tibial anterior, o que não ocorreu no músculo sóleo.
Asunto(s)
Humanos , Animales , Masculino , Benzaldehídos/farmacología , Músculo Esquelético/efectos de los fármacos , Tejido Conectivo/efectos de los fármacos , Neuropatía Ciática/patología , Antiinflamatorios/farmacología , Distribución Aleatoria , Ratas Wistar , Músculo Esquelético/patología , Fibras Musculares Esqueléticas/efectos de los fármacos , Tejido Conectivo/patología , Neuropatía Ciática/rehabilitación , Modelos AnimalesRESUMEN
The objective of this study was to evaluate three energy densities of low-level laser therapy (LLLT, GaAlAs, 780 nm, 40 mW, 0.04 cm2) for the treatment of lesions to peripheral nerves using the sciatic nerve of rats injured via crushing model (15 kgf, 5.2 MPa). Thirty Wistar rats (â, 200-250 g) were divided into five groups (n = 6): C-control, not injured, and irradiated; L0-injured nerve without irradiation; L4-injured nerve irradiated with LLLT 4 J/cm2 (0.16 J); L10-injured nerve irradiated with LLLT 10 J/cm2 (0.4 J); and L50-injured nerve irradiated with LLLT 50 J/cm2 (2 J). The animals were sacrificed 2 weeks after the injury via perfusion with glutaraldehyde (2.5%, 0.1 M sodium cacodylate buffer). The nerve tissue was embedded in historesin, cut (3 µm), mounted on slides, and stained (Sudan black and neutral red). The morphological and quantitative analysis (myelin and blood capillary densities) and morphometric parameters (maximum and minimum diameters of nerve fibers, axon diameter, G-ratio, myelin sheath thickness) were assessed using the ImageJ software. ANOVA (parametric) or Kruskal-Wallis (nonparametric) tests were used for the statistical analysis. Groups L0, L4, L10, and L50 exhibited diminished values of all the quantitative and morphometric parameters in comparison to the control group. The morphological, quantitative, and morphometric data revealed improvement after injury in groups L4, L10, and L50 (irradiated groups) compared to the injured-only group (L0); the best results, in general, were observed for the L10 group after 15 days of nerve injury.
Asunto(s)
Terapia por Luz de Baja Intensidad/métodos , Compresión Nerviosa , Nervio Ciático/patología , Nervio Ciático/efectos de la radiación , Neuropatía Ciática/patología , Animales , Capilares/patología , Capilares/efectos de la radiación , Masculino , Vaina de Mielina/metabolismo , Ratas Wistar , Nervio Ciático/irrigación sanguíneaRESUMEN
Background. To investigate the climb stairs resistance exercise on nociception and axonal regeneration in the sciatic nerve of rats. Methods. 24 Wistar rats were divided: control group (CG-no injury), exercise group (EG-no injury with physical exercise), lesion group (LG-injury, but without exercise), and treated group (LEG-injury and physical exercise). LG and LEG were subjected to sciatic nerve compression with hemostat. From the 3rd day after injury began treatment with exercise, and after 22 days occurs the removal of a nerve fragment for morphological analysis. Results. Regarding allodynia, CG obtained values less than EG (p = 0.012) and larger than LG and LEG (p < 0.001). Histological results showed that CG and EG had normal appearance, as LG and LEG showed up with large amounts of inflammatory infiltration, degeneration and disruption of nerve fibers, and reduction of the myelin sheath; however LEG presented some regenerated fibers. From the morphometric data there were significant differences, for nerve fiber diameter, comparing CG with LG and LEG and comparing axon diameter and the thickness of the myelin of the CG to others. Conclusion. Climb stairs resistance exercise was not effective to speed up the regenerative process of axons.
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Artrogriposis/complicaciones , Axones/patología , Terapia por Ejercicio , Neuropatía Hereditaria Motora y Sensorial/complicaciones , Neuropatía Ciática , Análisis de Varianza , Animales , Modelos Animales de Enfermedad , Hiperalgesia/diagnóstico , Hiperalgesia/etiología , Fibras Nerviosas/patología , Umbral del Dolor , Condicionamiento Físico Animal , Modalidades de Fisioterapia , Ratas , Ratas Wistar , Neuropatía Ciática/etiología , Neuropatía Ciática/patología , Neuropatía Ciática/rehabilitaciónRESUMEN
Brachial plexus lesion results in loss of motor and sensory function, being more harmful in the neonate. Therefore, this study evaluated neuroprotection and regeneration after neonatal peripheral nerve coaptation with fibrin sealant. Thus, P2 neonatal Lewis rats were divided into three groups: AX: sciatic nerve axotomy (SNA) without treatment; AX+FS: SNA followed by end-to-end coaptation with fibrin sealant derived from snake venom; AX+CFS: SNA followed by end-to-end coaptation with commercial fibrin sealant. Results were analyzed 4, 8, and 12 weeks after lesion. Astrogliosis, microglial reaction, and synapse preservation were evaluated by immunohistochemistry. Neuronal survival, axonal regeneration, and ultrastructural changes at ventral spinal cord were also investigated. Sensory-motor recovery was behaviorally studied. Coaptation preserved synaptic covering on lesioned motoneurons and led to neuronal survival. Reactive gliosis and microglial reaction decreased in the same groups (AX+FS, AX+CFS) at 4 weeks. Regarding axonal regeneration, coaptation allowed recovery of greater number of myelinated fibers, with improved morphometric parameters. Preservation of inhibitory synaptic terminals was accompanied by significant improvement in the motor as well as in the nociceptive recovery. Overall, the present data suggest that acute repair of neonatal peripheral nerves with fibrin sealant results in neuroprotection and regeneration of motor and sensory axons.
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Adhesivo de Tejido de Fibrina/administración & dosificación , Regeneración Nerviosa/fisiología , Recuperación de la Función/fisiología , Neuropatía Ciática/tratamiento farmacológico , Animales , Animales Recién Nacidos , Supervivencia Celular/fisiología , Regeneración Nerviosa/efectos de los fármacos , Ratas , Ratas Endogámicas Lew , Recuperación de la Función/efectos de los fármacos , Nervio Ciático/efectos de los fármacos , Nervio Ciático/patología , Nervio Ciático/fisiología , Neuropatía Ciática/patología , Venenos de Serpiente , Factores de TiempoRESUMEN
Several reports have linked the presence of high titers of anti-Gg Abs with delayed recovery/poor prognosis in GBS. In most cases, failure to recover is associated with halted/deficient axon regeneration. Previous work identified that monoclonal and patient-derived anti-Gg Abs can act as inhibitory factors in an animal model of axon regeneration. Further studies using primary dorsal root ganglion neuron (DRGn) cultures demonstrated that anti-Gg Abs can inhibit neurite outgrowth by targeting gangliosides via activation of the small GTPase RhoA and its associated kinase (ROCK), a signaling pathway common to other established inhibitors of axon regeneration. We aimed to study the molecular basis of the inhibitory effect of anti-Gg abs on neurite outgrowth by dissecting the molecular dynamics of growth cones (GC) cytoskeleton in relation to the spatial-temporal analysis of RhoA activity. We now report that axon growth inhibition in DRGn induced by a well characterized mAb targeting gangliosides GD1a/GT1b involves: i) an early RhoA/ROCK-independent collapse of lamellipodia; ii) a RhoA/ROCK-dependent shrinking of filopodia; and iii) alteration of GC microtubule organization/and presumably dynamics via RhoA/ROCK-dependent phosphorylation of CRMP-2 at threonine 555. Our results also show that mAb 1B7 inhibits peripheral axon regeneration in an animal model via phosphorylation/inactivation of CRMP-2 at threonine 555. Overall, our data may help to explain the molecular mechanisms underlying impaired nerve repair in GBS. Future work should define RhoA-independent pathway/s and effectors regulating actin cytoskeleton, thus providing an opportunity for the design of a successful therapy to guarantee an efficient target reinnervation.
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Anticuerpos/farmacología , Microtúbulos/patología , Regeneración Nerviosa/efectos de los fármacos , Proteínas del Tejido Nervioso/metabolismo , Neuronas/citología , Polisacáridos/inmunología , Proteína de Unión al GTP rhoA/metabolismo , Animales , Animales Recién Nacidos , Células Cultivadas , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Ganglios Espinales/citología , Regulación de la Expresión Génica/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular , Microtúbulos/efectos de los fármacos , Regeneración Nerviosa/fisiología , Neuritas/efectos de los fármacos , Neuritas/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ratas , Ratas Wistar , Neuropatía Ciática/metabolismo , Neuropatía Ciática/patología , Transducción de SeñalRESUMEN
PPARγ is a ligand-activated nuclear receptor best known for its involvement in adipogenesis and glucose homeostasis. PPARγ activity has also been associated with neuroprotection in different neurological disorders, but the mechanisms involved in PPARγ effects in the nervous system are still unknown. Here we describe a new functional role for PPARγ in neuronal responses to injury. We found both PPAR transcripts and protein within sensory axons and observed an increase in PPARγ protein levels after sciatic nerve crush. This was correlated with increased retrograde transport of PPARγ after injury, increased association of PPARγ with the molecular motor dynein, and increased nuclear accumulation of PPARγ in cell bodies of sensory neurons. Furthermore, PPARγ antagonists attenuated the response of sensory neurons to sciatic nerve injury, and inhibited axonal growth of both sensory and cortical neurons in culture. Thus, axonal PPARγ is involved in neuronal injury responses required for axonal regeneration. Since PPARγ is a major molecular target of the thiazolidinedione (TZD) class of drugs used in the treatment of type II diabetes, several pharmaceutical agents with acceptable safety profiles in humans are available. Our findings provide motivation and rationale for the evaluation of such agents for efficacy in central and peripheral nerve injuries.
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Axones/metabolismo , Regulación de la Expresión Génica/fisiología , Regeneración Nerviosa/fisiología , Neuronas/patología , PPAR gamma/metabolismo , Neuropatía Ciática/patología , Anilidas/farmacología , Animales , Axones/efectos de los fármacos , Axotomía , Células Cultivadas , Embrión de Mamíferos , Ganglios Espinales/patología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas de Neurofilamentos/metabolismo , Fármacos Neuroprotectores/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
Previous studies by our group demonstrated the key role of iron in Schwann cell maturation through an increase in cAMP, PKA activation and CREB phosphorylation. These studies opened the door to further research on non-transferrin-bound iron uptake, which revealed the presence of DMT1 mRNA all along SC progeny, hinting at a constitutive role of DMT1 in ensuring the provision of iron in the PNS. In light of these previous results, the present work evaluates the participation of DMT1 in the remyelination process following a demyelinating lesion promoted by sciatic nerve crush--a reversible model of Wallerian degeneration. DMT1 was observed to colocalize with a SC marker S100ß at all survival times analyzed. In turn, the assessment of DMT1 mRNA expression exhibited an increase 7 days post-injury, while DMT1 protein levels showed an increase 14 days after crush at the lesion site and distal stump; finally, an increase in iron levels became evident as from 14 days post-injury, in parallel with DMT1 values. To sum up, the present work unveils the role of DMT1 in mediating the neuroregenerative action of iron.
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Proteínas de Transporte de Catión/metabolismo , Hierro/metabolismo , Sistema Nervioso Periférico/metabolismo , Animales , Western Blotting , Proteínas de Transporte de Catión/genética , Vaina de Mielina/metabolismo , Sistema Nervioso Periférico/patología , Ratas , Ratas Wistar , Neuropatía Ciática/metabolismo , Neuropatía Ciática/patología , Degeneración Walleriana/metabolismo , Degeneración Walleriana/patologíaRESUMEN
BACKGROUND: It has recently become evident that activating/inhibitory cell surface immune receptors play a critical role in regulating immune and inflammatory processes in the central nervous system (CNS). The immunoreceptor CD300f expressed on monocytes, neutrophils, and mast cells modulates inflammation, phagocytosis, and outcome in models of autoimmune demyelination, allergy, and systemic lupus erythematosus. On the other hand, a finely regulated inflammatory response is essential to induce regeneration after injury to peripheral nerves since hematogenous macrophages, together with resident macrophages and de-differentiated Schwann cells, phagocyte distal axonal and myelin debris in a well-orchestrated inflammatory response. The possible roles and expression of CD300f and its ligands have not been reported under these conditions. METHODS: By using quantitative PCR (QPCR) and CD300f-IgG2a fusion protein, we show the expression of CD300f and its ligands in the normal and crush injured sciatic nerve. The putative role of CD300f in peripheral nerve regeneration was analyzed by blocking receptor-ligand interaction with the same CD300f-IgG2a soluble receptor fusion protein in sciatic nerves of Thy1-YFP-H mice injected at the time of injury. Macrophage M1/M2 polarization phenotype was also analyzed by CD206 and iNOS expression. RESULTS: We found an upregulation of CD300f mRNA and protein expression after injury. Moreover, the ligands are present in restricted membrane patches of Schwann cells, which remain stable after the lesion. The lesioned sciatic nerves of Thy1-YFP-H mice injected with a single dose of CD300f-IgG2a show long lasting effects on nerve regeneration characterized by a lower number of YFP-positive fibres growing into the tibial nerve after 10 days post lesion (dpl) and a delayed functional recovery when compared to PBS- or IgG2a-administered control groups. Animals treated with CD300f-IgG2a show at 10 dpl higher numbers of macrophages and CD206-positive cells and lower levels of iNOS expression than both control groups. At later time points (28 dpl), increased numbers of macrophages and iNOS expression occur. CONCLUSIONS: Taken together, these results show that the pair CD300f ligand is implicated in Wallerian degeneration and nerve regeneration by modulating both the influx and phenotype of macrophages.
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Inflamación/patología , Macrófagos/patología , Regeneración Nerviosa , Receptores Inmunológicos/genética , Animales , Axones/patología , Células CHO , Cricetinae , Cricetulus , Femenino , Inmunoglobulina G/biosíntesis , Inmunoglobulina G/genética , Lectinas Tipo C/metabolismo , Ligandos , Masculino , Receptor de Manosa , Lectinas de Unión a Manosa/metabolismo , Ratones , Compresión Nerviosa , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Nervios Periféricos/patología , Fagocitosis , Fenotipo , Receptores de Superficie Celular/metabolismo , Células de Schwann/patología , Neuropatía Ciática/patología , Degeneración Walleriana/patologíaRESUMEN
INTRODUCTION: In this study we evaluated the characteristics of the tibialis anterior muscle after sciatic nerve crush and treatment with low-level laser therapy (LLLT) or the protein from natural latex (P1). METHODS: We studied the following 6 groups of male Wistar rats: control (CG); exposed nerve (EG); injured nerve (IG); injured nerve with LLLT (LG); injured nerve with P1 (PG); and injured nerve with P1 and LLLT (LPG). RESULTS: After 4 weeks, muscle morphology showed improvement in the treated groups; after 8 weeks, the treated groups resembled controls, especially the PG. Morphometry revealed muscle fiber atrophy after nerve injury, with time-dependent recovery. Histochemical analysis revealed increased intermediate fiber area. The PG was more similar to controls with NADH staining, whereas the LPG more closely resembled controls with SDH staining. CONCLUSION: Treatment using only P1 proved most efficient, revealing a negative interaction between P1 and LLLT.
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Hevea , Terapia por Láser/métodos , Látex/uso terapéutico , Compresión Nerviosa , Neuropatía Ciática/terapia , Animales , Látex/aislamiento & purificación , Terapia por Luz de Baja Intensidad/métodos , Masculino , Ratas , Ratas Wistar , Neuropatía Ciática/patología , Resultado del TratamientoRESUMEN
This study evaluated the effect of low-level laser therapy (LLLT; 15 J/cm(2)) and a latex protein (F1) on a crush injury of the sciatic (ischiadicus) nerve. Seventy-two rats (male, 250 g) were divided into 6 groups: CG, control; EG, exposed nerve; IG, injured nerve without treatment; LG, injured nerve with LLLT; HG, injured nerve with F1; and LHG, injured nerve with LLLT and F1. After 4 or 8 weeks, the animals were euthanized and samples of the sciatic nerve were collected for morphometric and high-resolution scanning electron microscopy (HRSEM) analysis. After 4 weeks, the morphometry revealed improvements in the treated animals, and the HG appeared to be the most similar to the CG; after 8 weeks, the injured groups showed improvements compared to the previous period, and the results of the treatment groups were more similar to one another. At HRSEM after 4 weeks, the treated groups were similar and showed improvement compared to the IG; after 8 weeks, the LHG and HG had the best results. In conclusion, the treatments resulted in improvement after the nerve injury, and this recovery was time-dependent. In addition, the use of the F1 resulted in the best morphometric and ultrastructural findings.