Structural brain changes after 4 wk of unilateral strength training of the lower limb.

Strength training enhances muscular strength and neural drive, but the underlying neuronal mechanisms remain unclear. This study used magnetic resonance imaging (MRI) to identify possible changes in corticospinal tract (CST) microstructure, cortical activation, and subcortical structure volumes following unilateral strength training of the plantar flexors. Mechanisms underlying cross-education of strength in the untrained leg were also investigated. Young, healthy adult volunteers were assigned to training (n = 12) or control (n = 9) groups. The 4 wk of training consisted of 16 sessions of 36 unilateral isometric plantar flexions. Maximum voluntary isometric contraction torque was tested pre- and posttraining. MRI investigation included a T1-weighted scan, diffusion tensor imaging and functional MRI. Probabilistic fiber tracking of the CST was performed on the diffusion tensor imaging images using a two-regions-of-interest approach. Fractional anisotropy and mean diffusivity were calculated for the left and right CST in each individual before and after training. Standard functional MRI analyses and volumetric analyses of subcortical structures were also performed. Maximum voluntary isometric contraction significantly increased in both the trained and untrained legs of the training group, but not the control group. A significant decrease in mean diffusivity was found in the left CST following strength training of the right leg. No significant changes were detected in the right CST. No significant changes in cortical activation were observed following training. A significant reduction in left putamen volume was found after training. This study provides the first evidence for strength training-related changes in white matter and putamen in the healthy adult brain.

Protease-activated receptor 2 mediates the proinflammatory effects of synovial mast cells.

OBJECTIVE: Mast cells are hypothesized to play a role in the pathogenesis of rheumatoid arthritis (RA) by mechanisms requiring elucidation. Tryptase released from these cells can activate protease-activated receptor 2 (PAR-2), which was recently shown to have proinflammatory actions. The purpose of this study was to examine the relationship between synovial mast cells and PAR-2. Mast cell proximity to PAR-2-expressing cells was investigated in RA synovium. In murine studies, we assessed the capacity of mast cell tryptase to mediate synovial proinflammatory responses via PAR-2 and whether degranulating mast cells induced synovial hyperemia by PAR-2 activation. METHODS: RA synovial tissue was examined by immunohistochemistry. PAR-2(+/+) and PAR-2(-/-) C57BL/6J mice were used to investigate the PAR-2 dependence of compound 48/80-induced synovial hyperemia, as measured by laser Doppler imaging, and joint swelling and hyperemic responses to recombinant human beta-tryptase. RESULTS: Mast cells and synovial lining cells staining for PAR-2 were colocalized in RA articular tissue. Compound 48/80 administration resulted in vasodilatation in PAR-2(+/+) mice but not in PAR-2(-/-) mice, which showed a vasoconstrictor response. Eliminating the 5-hydroxytryptamine-mediated component of this response with methysergide unveiled an enhanced PAR-2-mediated vasodilatation to compound 48/80 in PAR-2(+/+) mice and ablated the vasoconstrictor response in PAR-2(-/-) mice. Treatment with beta-tryptase resulted in dose-dependent knee joint swelling and synovial vasodilatation in PAR-2(+/+) mice but not PAR-2(-/-) mice. CONCLUSION: This in vivo study is the first to explore the relationship between synovial mast cells and PAR-2. Our results support the hypothesis that mast cells contribute to the pathogenesis of inflammatory arthritis through PAR-2 activation via release of mast cell tryptase.