Detraining ablates exercise-induced modulation of the immune system after stroke

Regular aerobic exercise promotes anti-inflammatory effects, reduces stroke risk, and improves post-stroke outcomes. Rodent studies investigating exercise-induced neuroprotection, however, overlook clinically-relevant aspects of exercise training, including changes in intensity, volume, and detraining-related effects. This study used voluntary exercise training to determine how natural variations in exercise volume and detraining after exercise affect post-stroke neuroinflammation. Outbred Swiss Webster (SW) male mice (8-10 weeks old at start) were given unrestricted access to exercise wheels for 3 weeks. A second cohort of detrained mice exercised for 3 weeks and remained inactive for an additional 2 weeks. Sedentary control cohorts were housed for the same durations of 3 or 5 weeks. Flow cytometry evaluated adaptive and innate immune cells isolated from brain and spleen following a 60-min transient middle cerebral artery occlusion (tMCAo). High volume exercise reduced T cell populations in the uninjured brain, while exercise of a consistent volume was associated with activated splenic B cell populations. While exercise did not significantly reduce infarct volumes, detraining increased infarct volumes over both sedentary and exercise cohorts and elevated splenic CD4, CD8, and natural killer (NK) T cell populations at day 3 post-tMCAo. Detraining ablated exercise-induced leukocyte diapedesis into the ischemic hemisphere. Therefore, exercise training prior to stroke modulates both innate and adaptive post-stroke immune responses depending on variability in exercise volume and detaining. Understanding how variations in exercise affect neuroinflammation after stroke has significant clinical implications, given the high variation in adherence to exercise protocols for older adults at greater risk for stroke.