Introduction. Stroke is a leading cause of death and disability globally and in Australia. Interestingly, physical activity and exercise is thought to reduce stroke risk; enhance rehabilitation following stroke; and in particular induce remodelling of cerebral blood vessels and their basement membranes, although the mechanisms underpinning these effects remain unclear. Perlecan is a major ECM protein of vascular basement membranes, neuromuscular junctions and cartilage, which is known to be proteolytically processed to release a C-terminal bioactive fragment: the LG3 peptide. Importantly, the LG3 peptide is naturally released in the stroke-injured brain and is profoundly neuroprotective / neuroreparative when administered systemically in animals. We have previously found that the LG3 peptide was increased in the urine of physically active mining workers compared to sedentary controls; however, no previous studies have investigated the relationship between physical activity and the changes in LG3 abundance in human serum where it might have therapeutic benefit.
Aims. To measure the serum levels of the LG3 peptide in response to exercise.
Methods. Venous blood was collected at pre- and post-exercise from six males following an intermittent, high-intensity exercise (85% VO2 max) and a continuous, moderate-intensity exercise (60% VO2 max). LG3 quantification was performed by quantitative mass spectrometry to specifically target the LG3 peptide in serum.
Results. LG3 peptide levels significantly increased in response to moderate-intensity exercise.
Discussion. These results suggest that circulating levels of the neuroprotective / neuroreparative LG3 peptide can be significantly increased under normal physiological conditions in healthy individuals following moderate exercise. We are currently undertaking a pilot clinical study to determine if patients with mild stroke can increase circulating levels of LG3 peptide with moderate to low levels of exercise. These studies may help establish a baseline level of physical activity required to elevate LG3 peptide to potentially beneficial levels in the blood.