Physical exercise therapy for autoimmune neuroinflammation: Application of knowledge from animal models to patient care

Einstein, Ofira; Katz, Abram; Ben‐Hur, Tamir

doi:10.1016/j.autrev.2022.103033

Cited by 13 publications

(4 citation statements)

References 145 publications

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“…Another group of recipient mice were injected with PLP-reactive encephalitogenic cells from SED mice and served as controls. This approach enabled assessment of whether treadmill running of the donor mice modulated the systemic autoimmune process: (1) in vivo by examination of the clinical severity and CNS inflammation of EAE in recipient na€ ıve SJL mice, following transfer of encephalitogenic cells from trained-vs. sedentary donor mice; and (2) in vitro, at the day of PLP-reactive LNCs removal or following secondary activation in vitro by the PLP auto-antigen, using chemokine receptor and integrin gene expression and surface integrin expression analyses.…”

Section: Experimental Designmentioning

confidence: 99%

“…A large body of evidence indicates beneficial outcomes of exercise training (ET) among multiple sclerosis (MS) patients and in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. 1 In a series of studies, we utilized the passive transfer EAE model that enabled differentiation between systemic immunomodulatory effects and direct neuroprotective effects of different training paradigms of ET. We first demonstrated peripheralsystemic immunomodulatory effects of moderate-intensity continuous training (MICT) in transfer EAE.…”

Section: Introductionmentioning

confidence: 99%

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Exercise training alters autoimmune cell invasion into the brain in autoimmune encephalomyelitis

Hamdi

Nabat

Goldberg

et al. 2022

Ann Clin Transl Neurol

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Background The mechanisms by which exercise training (ET) elicits beneficial effects on the systemic immune system and the central nervous system (CNS) in autoimmune neuroinflammation are not fully understood. Objectives To investigate (1) the systemic effects of high‐intensity continuous training (HICT) on the migratory potential of autoimmune cells; (2) the direct effects of HICT on blood–brain‐barrier (BBB) properties. Methods Healthy mice were subjected to high‐intensity continuous training (HICT) by treadmill running. The proteolipid protein (PLP) transfer EAE model was utilized to examine the immunomodulatory effects of training, where PLP‐reactive lymph‐node cells (LNCs) from HICT and sedentary donor mice were analyzed in vitro and transferred to naïve recipients that developed EAE. To examine neuroprotection, encephalitogenic LNCs from donor mice were transferred into HICT or sedentary recipient mice and the BBB was analyzed. Results Transfer of PLP‐reactive LNCs obtained from HICT donor mice attenuated EAE severity and inflammation in recipient mice. HICT markedly inhibited very late antigen (VLA)‐4 and lymphocyte function‐associated antigen (LFA)‐1 expression in LNCs. Transfer of encephalitogenic LNCs into HICT recipients resulted in milder EAE and attenuated CNS inflammation. HICT reduced BBB permeability and the expression of intercellular adhesion molecule (ICAM)‐1 and vascular cell adhesion molecule (VCAM)‐1 in CNS blood vessels. Interpretation HICT attenuates EAE development by both immunomodulatory and neuroprotective effects. The reduction in destructive CNS inflammation in EAE is attributed to systemic inhibition of autoreactive cell migratory potential, as well as reduction in BBB permeability, which are associated with reduced VLA‐4/VCAM‐1 and LFA‐1/ICAM‐1 interactions.

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Section: Experimental Designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exercise training alters autoimmune cell invasion into the brain in autoimmune encephalomyelitis

Hamdi

Nabat

Goldberg

et al. 2022

Ann Clin Transl Neurol

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“…Physical exercise was also suggested to be involved in neuroprotective mechanisms. The importance of researching the optimization of physical exercise to achieve neuroprotection [ 164 ], was concluded by the author. Song examined the role of hydroxyfasudil (HF) on oxidative stress in experimental autoimmune encephalomyelitis (EAE) mice and its possible mechanisms.…”

Section: Autoimmune and Rheumatic Diseases During Auto13: (Diseases 1–9)mentioning

confidence: 99%

The mosaic of autoimmunity – Finally discussing in person. The 13th international congress on autoimmunity 2022 (AUTO13) Athens

Mahroum

Elsalti

Alwani

et al. 2022

Autoimmunity Reviews

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“…Beneficial outcomes of exercise training (ET) in multiple sclerosis (MS) patients are well documented 1 , 2 . Various mechanisms have been suggested to underlie the beneficial effects of ET in experimental autoimmune encephalomyelitis (EAE), an animal model of MS 3 . Accordingly, in a series of studies, we utilized the passive transfer EAE model, that enabled us to differentiate between systemic immunomodulatory and direct neuroprotective effects of ET, to examine the impact of various training paradigms on the progression of EAE 4 – 8 .…”

Section: Introductionmentioning

confidence: 99%

High-intensity interval training attenuates development of autoimmune encephalomyelitis solely by systemic immunomodulation

Goldberg,

Segal,

Hamdi

et al. 2023

Sci Rep

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The impact of high-intensity interval training (HIIT) on the central nervous system (CNS) in autoimmune neuroinflammation is not known. The aim of this study was to determine the direct effects of HIIT on the CNS and development of experimental autoimmune encephalomyelitis (EAE). Healthy mice were subjected to HIIT by treadmill running and the proteolipid protein (PLP) transfer EAE model was utilized. To examine neuroprotection, PLP-reactive lymph-node cells (LNCs) were transferred to HIIT and sedentary (SED) mice. To examine immunomodulation, PLP-reactive LNCs from HIIT and SED donor mice were transferred to naïve recipients and analyzed in vitro. HIIT in recipient mice did not affect the development of EAE following exposure to PLP-reactive LNCs. HIIT mice exhibited enhanced migration of systemic autoimmune cells into the CNS and increased demyelination. In contrast, EAE severity in recipient mice injected with PLP-reactive LNCs from HIIT donor mice was significantly diminished. The latter positive effect was associated with decreased migration of autoimmune cells into the CNS and inhibition of very late antigen (VLA)-4 expression in LNCs. Thus, the beneficial effect of HIIT on EAE development is attributed solely to systemic immunomodulatory effects, likely because of systemic inhibition of autoreactive cell migration and reduced VLA-4 integrin expression.

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Physical exercise therapy for autoimmune neuroinflammation: Application of knowledge from animal models to patient care

Cited by 13 publications

References 145 publications

Exercise training alters autoimmune cell invasion into the brain in autoimmune encephalomyelitis

Exercise training alters autoimmune cell invasion into the brain in autoimmune encephalomyelitis

The mosaic of autoimmunity – Finally discussing in person. The 13th international congress on autoimmunity 2022 (AUTO13) Athens

High-intensity interval training attenuates development of autoimmune encephalomyelitis solely by systemic immunomodulation

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