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Exercise: finding the good in inflammation using models of MS
B.T. Lund, A.M. Levy, G. Agadjanyan, E.E. Kelland Neurology, University of Southern California, Los Angeles, CA, United States
Background: Recent studies have shown that the brain is capable of recovering from injury and that this recovery can be enhanced with exercise and environmental stimuli which are new to the individual. Exercise has multiple biological effects in the brain and on the peripheral immune system, both of which are involved in the disease processes that we see in MS. Exercise is associated with neurogenesis and synaptogenesis, and can inhibit inflammatory processes. We assessed the mechanisms of exercise intervention in the early stages of demyelinating disease using the experimental allergic encephalomyelitis (EAE) model of MS. Assessing the effect of exercise in models of MS allowed us to remove the confounds of concomitant medications and lifestyles.
Methods: Our experimental approach evaluated the effects of exercise on clinical course, pathological hallmarks of disease, and adaptive and innate immune responses. We assessed the effect of exercise intervention, in the form of daily treadmill running, in a relapsing-remitting model (PLP-EAE: PLP inoculation in SJL/J mice) and a more chronic progressive model (MOG-EAE: MOG inoculation in C57BL6/J mice). Exercise was started only after recovery from the acute phase in PLP-EAE or after mice showed accrued disability (>1.0) in MOG-EAE. Clinical effects were compared to control EAE littermates subjected to the same environmental stimuli but which did not undergo an exercise regimen.
Results: Exercise was associated with almost complete attenuation of clinical disease in the PLP-EAE model. In MOG-EAE, exercise was associated with a dramatic reduction in clinical disease, though these mice still accrued mild disability. Analyses of spinal cord tissue showed that there was a significant reduction in disease pathology in exercised mice: reduced lesion number, lesion volume and inflammatory infiltrate. Exercise was also associated with significant changes in the immune response: reduced antigen-specific (PLP or MOG) proliferative responses, increased secretion of anti-inflammatory cytokines, reduction in typical pro-inflammatory cytokines, and changes in the mononuclear cells recruited to the CNS both at early and late stages of exercise intervention.
Conclusions: Exercise is associated with a beneficial, neuroprotective, anti-inflammatory response in animal models of demyelinating disease. These data suggest that appropriate exercise intervention may be a useful approach to the treatment of early stages MS.
B.T. Lund, A.M. Levy, G. Agadjanyan, E.E. Kelland Neurology, University of Southern California, Los Angeles, CA, United States
Background: Recent studies have shown that the brain is capable of recovering from injury and that this recovery can be enhanced with exercise and environmental stimuli which are new to the individual. Exercise has multiple biological effects in the brain and on the peripheral immune system, both of which are involved in the disease processes that we see in MS. Exercise is associated with neurogenesis and synaptogenesis, and can inhibit inflammatory processes. We assessed the mechanisms of exercise intervention in the early stages of demyelinating disease using the experimental allergic encephalomyelitis (EAE) model of MS. Assessing the effect of exercise in models of MS allowed us to remove the confounds of concomitant medications and lifestyles.
Methods: Our experimental approach evaluated the effects of exercise on clinical course, pathological hallmarks of disease, and adaptive and innate immune responses. We assessed the effect of exercise intervention, in the form of daily treadmill running, in a relapsing-remitting model (PLP-EAE: PLP inoculation in SJL/J mice) and a more chronic progressive model (MOG-EAE: MOG inoculation in C57BL6/J mice). Exercise was started only after recovery from the acute phase in PLP-EAE or after mice showed accrued disability (>1.0) in MOG-EAE. Clinical effects were compared to control EAE littermates subjected to the same environmental stimuli but which did not undergo an exercise regimen.
Results: Exercise was associated with almost complete attenuation of clinical disease in the PLP-EAE model. In MOG-EAE, exercise was associated with a dramatic reduction in clinical disease, though these mice still accrued mild disability. Analyses of spinal cord tissue showed that there was a significant reduction in disease pathology in exercised mice: reduced lesion number, lesion volume and inflammatory infiltrate. Exercise was also associated with significant changes in the immune response: reduced antigen-specific (PLP or MOG) proliferative responses, increased secretion of anti-inflammatory cytokines, reduction in typical pro-inflammatory cytokines, and changes in the mononuclear cells recruited to the CNS both at early and late stages of exercise intervention.
Conclusions: Exercise is associated with a beneficial, neuroprotective, anti-inflammatory response in animal models of demyelinating disease. These data suggest that appropriate exercise intervention may be a useful approach to the treatment of early stages MS.