Electrical Stimulation Prevents Muscular Atrophy and the Decrease of Interleukin-6 in Paralyzed Muscles after Spinal Cord Injury in Rats.

Objective To analyze the muscle trophism and expression of interleukin-6 in the biceps brachii muscle of rats with incomplete cervical spinal cord injury treated with neuromuscular electrical stimulation (NMES). Methods Adult rats underwent C5-C7 spinal cord hemisection and a 5-week NMES protocol. Trophism of the biceps brachii was assessed using muscle weight/body weight ratio and histological analysis. Interleukin-6 expression from biceps brachii was measured using the enzyme-linked immunosorbent assay technique. Results Preservation of the biceps brachii muscle trophism was found in the NMES treated group, along with prevention of the reduction of interleukin-6 levels. Conclusion Spinal cord injury causes muscle atrophy and decreases interleukin-6 levels. These alterations are partially prevented by NMES. The results suggest a possible NMES action mechanism and underscore the clinical use of this therapeutic tool.

Electrical Stimulation Prevents Muscular Atrophy and the Decrease of Interleukin-6 in Paralyzed Muscles after Spinal Cord Injury in Rats / A estimulação elétrica previne a atrofia muscular e a diminuição da interleucina-6 em músculos paralisados após lesão da medula espinal em ratos

Abstract Objective To analyze the muscle trophism and expression of interleukin-6 in the biceps brachii muscle of rats with incomplete cervical spinal cord injury treated with neuromuscular electrical stimulation (NMES). Methods Adult rats underwent C5-C7 spinal cord hemisection and a 5-week NMES protocol. Trophism of the biceps brachii was assessed using muscle weight/body weight ratio and histological analysis. Interleukin-6 expression from biceps brachii was measured using the enzyme-linked immunosorbent assay technique. Results Preservation of the biceps brachii muscle trophism was found in the NMES treated group, along with prevention of interleukin-6 level reduction. Conclusion Spinal cord injury causes muscle atrophy and decreases interleukin-6 levels. These alterations are partially prevented by NMES. The results suggest a possible NMES action mechanism and underscore the clinical use of this therapeutic tool.

Resumo Objetivo Analisar o trofismo muscular e a de interleucina-6 no músculo bíceps braquial de ratas com lesão medular cervical incompleta tratados com estimulação elétrica neuromuscular (EENM). Métodos Ratas adultas foram submetidas à hemissecção da medula espinal em C5-C7 e a um protocolo de EENM de 5 semanas. O trofismo do bíceps braquial foi avaliado pela relação peso muscular/peso corporal e análise histológica. A expressão de interleucina-6 no bíceps braquial foi medida usando ensaio de imunoabsorção enzimática. Resultados O grupo tratado com EENM apresentou preservação do trofismo muscular, assim como prevenção da redução dos níveis de interleucina-6. Conclusão A lesão da medula espinal causa atrofia muscular e diminui a expressão de interleucina-6. Essas alterações são parcialmente prevenidas pela EENM. Os resultados sugerem um possível mecanismo de ação da EENM e ressaltam o uso clínico desta ferramenta terapêutica.

Manipulation of the Fascial System Applied During Acute Inflammation of the Connective Tissue of the Thoracolumbar Region Affects Transforming Growth Factor-ß1 and Interleukin-4 Levels: Experimental Study in Mice.

Fascia can become rigid and assume a fibrotic pattern due to inflammatory processes. Manipulation of the fascial system (MFS), manual technique targeting connective tissues, is commonly used in clinical practice in pain management. We aimed to verify MFS effects on the connective tissue inflammatory changes in mice. Swiss Mus musculus male mice (n = 44) were distributed into groups: carrageenan without treatment (Car, n = 11), carrageenan with MFS (Car + MFS, n = 12), saline without treatment (n = 10), and saline with MFS (saline + MFS, n = 11). Interleukin 4 (IL-4), IL-6, tumor necrosis factor (TNF), transforming growth factor ß1 (TGF-ß1), and monocyte chemoattractant protein 1 (MCP-1) levels were verified by enzyme-linked immunosorbent assay. Neutrophil (Ly-6G), macrophage (F4/80), and nitric oxide synthase 2 (NOS-2) were identified using Western blot. The MFS protocol was applied from the first to the third day after inflammation of the connective tissue of the thoracolumbar region. There was a significant MFS effect on IL-4 (p = 0.02) and TGF-ß1 (p = 0.04), without increasing MCP-1, TNF, and IL-6 levels (p > 0.05) on thoracolumbar region from Car + MFS, in comparison with saline. Ly-6G in Car + MFS presented lower levels when compared with saline (p = 0.003) or saline + MFS (0.003). NOS-2 levels were lower in Car + MFS than in saline + MFS (p = 0.0195) or saline (p = 0.003). MFS may have an anti-inflammatory effect, based on TGF-ß1 and IL-4. IL-4 may have inhibited neutrophil migration. Lower levels of NOS-2 may be linked to the lack of macrophages, which are responsible for NOS-2 expression.

Overground gait training promotes functional recovery and cortical neuroplasticity in an incomplete spinal cord injury model.

AIM: Evidence suggests that task-specific gait training improves locomotor impairments in people with incomplete spinal cord injury (SCI); however, plastic changes in brain areas remain poorly understood. The aim of this study was to examine the possible effects of a task-specific overground gait training on locomotor recovery and neuroplasticity markers in the cortex, cerebellum, and lumbar spinal cord in an experimental model of incomplete-SCI. MAIN METHODS: Using a blind, basic experimental design, 24 adult Wistar rats underwent a surgical procedure and were allocated into sham, non-trained SCI (SCI), and trained SCI (Tr-SCI) groups. On postoperative day 14, trained animals started a 4-week overground gait training program. All groups were subjected to weekly assessment of locomotor recovery of the hind limbs. On postoperative day 40, brain and lumbar spinal cord structures were dissected and processed for biochemical analysis of the synaptophysin, microtubule-associated protein 2 (MAP-2), and brain-derived neurotrophic factor (BDNF). KEY FINDINGS: Tr-SCI group showed greater locomotor function recovery compared with non-trained SCI from the postoperative day 21 (p < 0.05). The training was able to improve the neuroplasticity markers synaptophysin, MAP-2, and BDNF expressions in motor cortex (p < 0.05), but not in the cerebellum and in the spinal cord for trained SCI group compared to non-trained. SIGNIFICANCE: Task-specific overground gait training improves locomotor recovery in a rat model of incomplete thoracic-SCI. Furthermore, training promotes motor cortex plasticity, evidenced for increasing expression of the neuroplasticity markers that may support the functional recovery.

Early Cyclical Neuromuscular Electrical Stimulation Improves Strength and Trophism by Akt Pathway Signaling in Partially Paralyzed Biceps Muscle After Spinal Cord Injury in Rats.

Background: Electrical stimulation is often used to treat weakness in people with spinal cord injury (SCI); however its efficacy for increasing strength and trophism is weak, and the mechanisms underlying the therapeutic benefits are unknown. Objective: The purpose of this study was to analyze the effects of neuromuscular electrical stimulation (NMES) on muscle function, trophism, and the Akt pathway signaling involved in muscular plasticity after incomplete SCI in rats. Design: This was an experimental study. Methods: Twenty-one adult female Wistar rats were divided into sham, SCI, and SCI plus NMES groups. In injured animals, SCI hemisection was induced by a surgical procedure at the C5-C7 level. The 5-week NMES protocol consisted of biceps brachii muscle stimulation 5 times per week, initiated 48 h after injury. Forepaw function and strength, biceps muscle trophism, and the expression of phosphorylated Akt, p70S6K, and GSK-3ß cellular anabolic pathway markers in stimulated muscle tissue were assessed. Results: There was an increase in bicep muscle strength in the NMES group compared with the untreated SCI group, from postoperative day 21 until the end of the evaluation period. Also, there was an increase in muscle trophism in the NMES group compared with the SCI group. Forelimb function gradually recovered in both the SCI group and the NMES group, with no differences between them. Regarding muscle protein expression, the NMES group had higher values for phospho-Akt, phospho-p70S6K, and phospho-GSK-3ß than did the SCI group. Limitations: The experimental findings were limited to an animal model of incomplete SCI and may not be fully generalizable to humans. Conclusions: Early cyclical NMES therapy was shown to increase muscle strength and induce hypertrophy after incomplete SCI in a rat model, probably by increasing phospho-Akt, phospho-p70S6K, and phospho-GSK-3ß signaling protein synthesis.