Aerobic training improves blood-brain barrier and neuronal apoptosis in experimental autoimmune encephalomyelitis

OBJECTIVE(S): Blood-brain barrier (BBB) permeability is central in multiple sclerosis (MS) pathophysiology, and exercise may improve BBB integrity. The current study investigated the prophylactic and/ or therapeutic role of aerobic exercise (EX) training on BBB integrity in experimental autoimmune encephalomyelitis (EAE). MATERIALS AND METHODS: Forty female Lewis rats were randomly divided into four groups. The experimental groups included: no-EAE induction+ no-exercise (no-EAE+ no-EX), no-EAE induction+ exercise (no-EAE+EX), EAE induction+ no-exercise (EAE+ no-EX), and EAE induction+ exercise (EAE+EX). The no-EAE+EX and EAE+EX groups performed six weeks of progressive aerobic exercise training. GFAP, angiopoietin 1 (Ang-1) expression, tight-junction (TJ) proteins of claudin-5 and occludin were measured as components of BBB integrity and the rate of neuronal apoptosis was evaluated in hippocampi. RESULTS: A significant increase in GFAP and Ang-1 expression (P<0.001) and conversely a down-regulation in TJ proteins (P<0.05) was found in the brains of the no-EAE+EX group compared with the no-EAE+ no-EX group. The expression of GFAP and Ang-1 proteins significantly increased in the hippocampi of the EAE+ no-EX group (P<0.001), whereas aerobic training (in the EAE+EX group) meaningfully reversed such increases (P<0.001). Besides, down-regulated TJ proteins and increased neuronal apoptosis induced by EAE induction (EAE+ no-EX group) were restored and reduced, respectively, by aerobic training in the CNS of the EAE+EX group (P<0.001). CONCLUSION: The provision of a six-week treadmill aerobic training buffered the detrimental effects of EAE on BBB integrity and consequently neuronal apoptosis.