Effect of resistance exercise training on plasma neurofilaments in multiple sclerosis: a proof of concept for future designs.

Multiple sclerosis (MS) is a dysimmune and neurodegenerative disease of the central nervous system that continues to be one of the main causes of non-traumatic disability in young people despite the recent availability of highly effective drugs. Exercise-based interventions seem to have a positive impact on the course of the disease although pathophysiological mechanisms responsible for this benefit remain unclear. This is a longitudinal study to examine the effects of a short-term training program on neurofilament plasma levels, a biomarker of axonal destruction, measured using the ultrasensitive single molecule array (SiMoA). Eleven patients completed a 6-week supervised resistance-training program of 18 sessions that consisted of 3 sets of 8-10 repetitions of 7 exercises. Median plasma neurofilament levels significantly decreased from baseline (6.61 pg/ml) to 1 week after training intervention (4.44 pg/ml), and this effect was maintained after 4 weeks of detraining (4.38 pg/ml). These results suggest a neuroprotective effect of resistance training in this population and encourage us to investigate further the beneficial impact of physical exercise and to emphasize the importance of lifestyle in MS.

Anti-Neuroinflammatory Potential of a Nectandra angustifolia (Laurel Amarillo) Ethanolic Extract.

Microglia, the resident macrophage-like population in the CNS, plays an important role in the pathogenesis of many neurodegenerative disorders. Nectandra genus is known to produce different metabolites with anti-inflammatory, anti-oxidant and analgesic properties. Although the species Nectandra angustifolia is popularly used for the treatment of different types of inflammatory processes, its biological effects on neuroinflammation have not yet been addressed. In this study, we have investigated the role of a Nectandra angustifolia ethanolic extract (NaE) in lipopolysaccharide (LPS)-induced neuroinflammation in vitro and in vivo. In LPS-activated BV2 microglial cells, NaE significantly reduced the induced proinflammatory mediators TNF-α, IL-1ß, IL-6, COX-2 and iNOS, as well as NO accumulation, while it promoted IL-10 secretion and YM-1 expression. Likewise, reduced CD14 expression levels were detected in microglial cells in the NaE+LPS group. NaE also attenuated LPS-induced ROS and lipid peroxidation build-up in BV2 cells. Mechanistically, NaE prevented NF-κB and MAPKs phosphorylation, as well as NLRP3 upregulation when added before LPS stimulation, although it did not affect the level of some proteins related to antioxidant defense such as Keap-1 and HO-1. Additionally, we observed that NaE modulated some activated microglia functions, decreasing cell migration, without affecting their phagocytic capabilities. In LPS-injected mice, NaE pre-treatment markedly suppressed the up-regulated TNF-α, IL-6 and IL-1ß mRNA expression induced by LPS in brain. Our findings indicate that NaE is beneficial in preventing the neuroinflammatory response both in vivo and in vitro. NaE may regulate microglia homeostasis, not only restraining activation of LPS towards the M1 phenotype but promoting an M2 phenotype.