Chronic mild hypoxia accelerates recovery from preexisting EAE by enhancing vascular integrity and apoptosis of infiltrated monocytes

Significance We show that when applied to preexisting disease in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, chronic mild hypoxia (CMH, 10% O2 ) accelerates clinical recovery, leading to long-term stable reductions in clinical score. This was underpinned by marked reductions in histopathological markers of disease, including lower levels of vascular disruption, leukocyte accumulation, and demyelination. Mechanistically, CMH reduced vascular expression of the endothelial activation molecule vascular cell adhesion molecule (VCAM-1), but increased expression of endothelial tight junction proteins and accelerated apoptotic removal of infiltrated monocytes during the remission phase of disease. These data offer insight into the use of mild hypoxia, either as a therapeutic option for treating MS or as a tool to identify potential molecular targets.