Abstract TP116: Effect of Voluntary Physical Activity on Circulating LG3 and Its Impact on Ischemic Stroke

Abstract

Physical activity (PA) is neuroprotective. However, the mechanism for the benefit of PA prior to ischemic stroke is not well understood. Circulating LG3 levels, a 25-kDa protein fragment of brain extracellular matrix proteoglycan (perlecan), increases with PA in humans. We showed that LG3 significantly reduces infarct volume following ischemic stroke. The aim of this study is to assess whether LG3 concentration increases with voluntary physical activity in mice and to determine how circulating LG3 concentration, prior to ischemic stroke, influences outcomes. Male mice (C57BL/6J, 8-9 weeks old, 21–24 g) were randomized into sedentary control group (individually housed in motorized running wheel cages with applied brakes) and an exercise group with access to running wheels. Blood draws were collected via submental method on day 1, 7, 14 and 20 of wheel activity prior to middle cerebral artery occlusion (MCAO), to evaluate LG3 concentration in serum. Following three weeks of voluntary PA or sedentary condition, 25 mice (sedentary n=13, exercise n=12) underwent transient distal MCAO for 60 min and were recovered for three days. In another study, 29 mice (sedentary n=15, exercise n=14) underwent transient proximal MCAO for 60 min. Calf muscles (soleus and gastrocnemius) and brain samples were collected for histology, protein analysis, and infarct volume assessment. We show that voluntary PA significantly reduces ischemic lesion volume compared to sedentary controls, following distal MCAO (15.2±8 vs 5.3±2 mm 3 ; P<0.0001, Figure 1). The analysis of LG3 concentration, neurofunction, as well as brain and muscle samples are currently ongoing. We expect that the findings will link LG3 concentration to the volume of exercise as well as the neuroprotection it confers in the setting of ischemic stroke.