Effects of photobiomodulation therapy on muscle function in individuals with multiple sclerosis.

BACKGROUND: In people with multiple sclerosis (pwMS), muscle fatigue and weakness are common issues that can interfere with daily activities. Photobiomodulation therapy (PBMT), comprising light in a 600-1100 nm bandwidth, is a low-level laser therapy thought to improve muscle performance in non-disease populations, in part, by improving mitochondrial function and thus, might be beneficial in pwMS. Given this potential, we aimed to investigate the effects of PBMT on muscle performance in pwMS, both in the short-term and over an extended period. METHODS: This study consisted of two parts with a randomized double-blind crossover design. In study I, muscle function was assessed in four sessions before and after PBMT in ambulatory pwMS (N = 17, F = 14) as follows: maximal voluntary contraction (MVC) and muscle fatigue of the right tibialis anterior (TA) muscle was compared at baseline and following a two-min submaximal fatiguing contraction. Then, PBMT was administered to the belly of TA muscle at different doses of energy of an active device (40 J, 80 J, 120 J) or placebo. The muscle function assessment was then repeated. OUTCOME VARIABLES: muscle force recovery (%), muscle fatigue (%). Statistical tests included McNemar's exact test, Wilcoxon signed-rank test, and the Friedman test. In study II, a subgroup from study I (N = 12, F = 11) received individualized doses (i.e., best dose-effect observed in study I) of active, or placebo PBMT, which was administered on the TA muscle for two weeks. Muscle function assessments were performed pre- and post-PBMT in four sessions similar to study I. OUTCOME VARIABLES: Baseline strength (N), endurance time (s), and muscle fatigue (%). The Wilcoxon signed-rank test was used for statistical analysis. Values are reported as mean (SD). RESULTS: In study I, participants who received a high dose of PBMT showed significant improvement in force recovery (101.89 % (13.55 %)) compared to the placebo group (96.3 % (18.48 %); p = 0.03). Muscle fatigue did not significantly improve with either active PBMT or placebo. In study II, active PBMT resulted in a significant improvement in muscle strength compared to both the baseline (pre-PBMT = 162.70 N (37.52 N); post-PBMT = 185.56 N (33.95 N); p = 0.01) and the placebo group (active PBMT: mean-change = 22.87 N (23.67 N); placebo: mean-change = -4.12 N (31.95 N); p = 0.02). Endurance time and muscle fatigue did not show significant improvement with either active PBMT or placebo. CONCLUSION: Our findings suggest that an individualized dose of PBMT might improve muscle performance, including force recovery and strength in individuals with mild-moderate MS. Therefore, PBMT might be a novel therapeutic modality, either as a standalone treatment or in combination with other interventions, to improve muscle performance in pwMS.

Photobiomodulation at 830 nm Reduced Nitrite Production by Peripheral Blood Mononuclear Cells Isolated from Multiple Sclerosis Subjects.

Background: Multiple sclerosis (MS) is a neurodegenerative condition characterized by high concentration of nitric oxide leading to the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), a condition known as nitrosative stress. ROS and RNS produce the inhibition of the mitochondrial electron transport chain leading to mitochondrial dysfunction, reduction of adenosine triphosphate, and death of neurons, producing severe and irreversible damage in the central nervous system of people with MS (PwMS). Current drug treatments for MS focus on the regulation of immune response in acute stages of disease, but they do not regulate nitrosative stress which is present in the acute and chronic stages of disease. Previously, our laboratory showed that photobiomodulation (PBM) on experimental autoimmune encephalomyelitis mice, the animal model of MS, reduced clinical severity of disease, gene expression of inducible nitric oxide synthase (iNOS), and the levels of nitrite in in vivo and in vitro experiments. Objective: We evaluated the effect of PBM on the regulation of nitrosative stress in PwMS. Methods: PBM was applied on peripheral blood mononuclear cells (PBMCs) obtained from PwMS to evaluate PBM on the regulation of nitrate as a marker of nitrosative stress. Results: PBM at 830 nm (10 J/cm2 at 72 h) reduced the levels of nitrite and this reduction was in relationship with the increase of interleukin-10 and the reduction of interferon-γ produced by the PBMCs regardless of the severity of disease present in the participants. Conclusions: PBM at 830 nm can potentially be used to reduce nitrosative stress at any point of disease in PwMS.

Photobiomodulation Modulates Interleukin-10 and Interferon Gamma Production by Mononuclear Cells from Healthy Donors and Persons with Multiple Sclerosis.

Background: Photobiomodulation (PBM) therapy was previously shown to reduce the clinical severity of disease and modulated pro- and anti-inflammatory cytokines in an animal model of multiple sclerosis (MS). Objective: Previous observations were extended to determine the effect of PBM therapy on peripheral blood mononuclear cells and CD4+ T cells isolated from persons with MS (PwMS) and healthy donors. Methods: Using an in vitro cell culture system, isolated cells were activated and treated with red or near-infrared light wavelengths to determine the effect of PBM on the production of interferon gamma and interleukin-10 (IL-10). Results: PBM modulated cytokine production in MS subjects and healthy donors in a dose- and wavelength-dependent manner, with MS subjects and healthy donors responding differently to administered light. In addition, disease severity affected the response of immune cells, for instance, 670 nm increased IL-10 production associated with increased disease severity. Conclusions: The data show that PBM therapy has the potential to modulate pro- and anti-inflammatory cytokines in PwMS over the course of disease. Further experiments applying PBM treatment directly on patients should be carried out with extreme caution to avoid severe imbalance in the immune response.

Pathogenesis of septal fibrosis of the liver. (An experimental study with a new model.).

Septal fibrosis is an important, frequent, and non-specific type of fibrosis associated with chronic liver diseases, but its pathogenesis is still poorly understood. An interesting model of septal fibrosis occurs in rats infected with the nematode Capillaria hepatica. This model was used to investigate the pathogenesis, site of origin, structure, and cell-types of septal fibrosis. Forty young adult Wistar rats were inoculated with 800 embryonated eggs of C. hepatica. Daily liver samples were obtained from the 20th to the 39th day after inoculation to cover the critical period when septal fibrosis usually starts. Routine histology, electron microscopy, immunohistochemistry, and indirect immunofluorescence were applied to the study of liver sections. Septal blood vessels were demonstrated by India ink perfusion of the portal vein system. Prominent angiogenesis was observed to precede collagen deposition. Besides angiogenesis and mesenchymal-cell mobilization, septal fibrosis was seen to originate from portal spaces and to course through acinar zone I in between sinusoids, inducing no alterations in them, with no evident participation of stellate hepatic cells. Septal fibrosis appeared as an adaptative type of response of the liver to chronic injury, which resulted in a new structure that is normal to other species and creates accessory vessels that drain portal blood into hepatic sinusoids.

Significance and fate of septal fibrosis of the liver.

Septal fibrosis commonly occurs during chronic diseases of the liver. It is experimentally reproduced in a proportion of rats treated with pig-serum, and in 100% of rats infected with Capillaria hepatica. These models have only been used in relatively short-term studies. To contribute to the natural history and significance of hepatic septal fibrosis it is important to disclose its fate after prolonged observation, and following partial or total withdrawal of its inciting cause. Adult Wistar rats were sacrificed 3, 6, 9 and 12 months following inoculation of 800 embryonated eggs of C. hepatica. Besides routine histology, liver sections were submitted to immunohistochemical, immunofluorescence and ultrastructural techniques for the identification of cells and extracellular matrix components present in the fibrous septa. Septal blood vessels were studied after portal vein perfusion with India-ink, while the hepatic functional profile and levels of anti-C. hepatica antibodies were determined in collected sera. Results revealed that all parasites were already dead 2 months from inoculation, and the accumulated eggs in the liver lost their capacity to embryonate around the 4th-6th month, when progressive reduction in the number of cells and in the amount of collagen occurred in the septa. Septal fibrosis persisted throughout the time of experimentation (12 months). This fibrosis was seen as a supporting stroma for septal vessels that conducted portal blood directly to the sinusoids. Thus, persistence of fibrosis was probably related to its morphological and functional association with blood vessels.