Post stroke OSA: the effect of intermittent hypoxia on cerebrovascular recovery.

<bold>Introduction:</bold> After ischemic stroke, the cerebrovascular recovery process can be complicated by pathologies such as obstructive sleep apnea (OSA), a highly prevalent respiratory disease. Intermittent hypoxia (IH), one of the key hallmarks of OSA, plays a major role in the deleterious effects of OSA. However the pathophysiological mechanisms of this stroke-IH syndrome interaction are unknown. <bold>Objective:</bold> To study the effect of IH on cerebrovascular recovery in a rat stroke model. <bold>Methods:</bold> Rats were subjected to an experimental stroke model with injection of malonate (2ul,3M) followed by exposure for 4, 7, 14, 28 or 56 days to intermittent hypoxia or normoxia (N). We characterized brain lesion size and microvascular plasticity using 4.7T MRI <italic>in vivo.</italic> Plasma was collected 3 days before malonate injection, then at D4, D14, D28 and D56 post-stroke, then metabolites were analyzed by non-targeted nuclear magnetic resonance spectroscopy. <bold>Results:</bold> Lesion size did not differ between IH and N. IH significantly increased blood-brain barrier permeability at D4, but had no impact at other time points. Also, IH increased vessel size index and blood volume at D28. In metabolomic experiments, IH decreased alanine and betaine at D4, and increased B-hydroxybutyrate at D29. <bold>Conclusion:</bold> Exposure to intermittent hypoxia moderately affects cerebral vascularization and metabolic profiles in a time-dependent manner. Ongoing studies include investigation of the underlying mechanisms, focusing on inflammation and oxidative stress in brain samples by immunohistochemistry, qPCR and metabolomic analysis. This may provide future therapeutic targets to alleviate the IH-induced impact on the brain after stroke.