Department of Physical Therapy, Faculty of Health Sciences, Ariel University, Ariel, Israel.
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
Ann Clin Transl Neurol. 2022 Nov;9(11):1792-1806. doi: 10.1002/acn3.51677. Epub 2022 Oct 10.
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.
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.
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.
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.
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.
运动训练（ET）通过何种机制对自身免疫性神经炎症中的全身免疫系统和中枢神经系统（CNS）产生有益影响，目前尚不完全清楚。
研究高强度连续训练（HICT）对自身免疫性细胞迁移潜能的全身性影响；（2）HICT 对血脑屏障（BBB）特性的直接影响。
通过跑步机跑步使健康小鼠接受高强度连续训练（HICT）。采用蛋白脂质蛋白（PLP）转移实验性自身免疫性脑脊髓炎（EAE）模型，观察训练的免疫调节作用，分析来自 HICT 和久坐不动的供体小鼠的 PLP 反应性淋巴结细胞（LNC），并在体外转移至发生 EAE 的幼稚受体。为了研究神经保护作用，将供体小鼠的致脑炎 LNC 转移到 HICT 或久坐不动的受体小鼠中，并分析 BBB。
来自 HICT 供体小鼠的 PLP 反应性 LNC 的转移可减轻受体小鼠 EAE 的严重程度和炎症。HICT 显著抑制 LNC 中非常晚期抗原（VLA）-4 和淋巴细胞功能相关抗原（LFA）-1 的表达。将致脑炎 LNC 转移到 HICT 受体中导致 EAE 较轻和 CNS 炎症减轻。HICT 降低了 BBB 通透性以及 CNS 血管中细胞间黏附分子（ICAM）-1 和血管细胞黏附分子（VCAM）-1 的表达。
HICT 通过免疫调节和神经保护作用来减轻 EAE 的发展。EAE 中破坏性 CNS 炎症的减少归因于自身反应性细胞迁移潜能的全身性抑制，以及 BBB 通透性的降低，这与 VLA-4/VCAM-1 和 LFA-1/ICAM-1 相互作用减少有关。
