EXPRESS: Chronic Intermittent Hypoxia Induces Persistent Venous Narrowing of Downstream Parenchymal Microvessels and Pial Veins in the Male Mouse Cortex

Chronic intermittent hypoxia (IH), a hallmark of sleep apnea, can lead to cerebral hypoperfusion and cognitive decline, though its precise impact on cerebral microcirculation remains unclear. This study investigated the longitudinal effects of 2-week chronic IH (8% O2, 6.5-min cycle for 6 hours/day) on brain microcirculation in the male mouse cortex. We observed a significant reduction in the diameters of pial veins (from 55 to 46 μm) and parenchymal venules (from 9.9 to 8.2 μm) after chronic IH relative to pre-IH conditions, while upstream arteries (47 to 44 μm) and arterioles (12.4 to 12.0 μm) were unaffected. This selective reduction in downstream venule diameter led to a significant increase in arterio-venous transit time, indicating reduced cerebral blood perfusion. Furthermore, neurovascular coupling (NVC) responses showed a substantial decrease, pointing to impaired microvascular function. Crucially, these neurovascular impairments were reversed by daily administration of an endothelin receptor antagonist during IH exposure, with the exception of pial vein constriction. In conclusion, reduced cerebral perfusion after chronic IH is associated with persistent narrowing of parenchymal venules and pial veins. These findings provide new insights into the cerebral microvascular complications of chronic IH and suggest the potential utility of neurovascular protective agents.