0055 Neuroinflammatory Damage in the Pre-Bötzinger Complex Contributes to the Central Mechanism by Which Intermittent Hypoxia Exacerbates Sleep Apnea

Abstract Introduction Research indicates that intermittent hypoxia (IH), a key factor in the progression of Obstructive Sleep Apnea (OSA), can exacerbate the condition. However, the underlying central neural mechanisms remain incompletely elucidated. Specifically, it is still unknown whether IH disrupts respiratory control by triggering neuroinflammation within the brainstem respiratory centers. Methods SD rats with surgically implanted cranial electrodes underwent sleep-breathing monitoring before and after a 4-week intermittent hypoxia (IH) exposure (10%-21% O₂, 120-second cycle, 8 h/day). The medullary respiratory centers were then collected for analysis. We performed immunofluorescence, immunohistochemistry, and Nissl staining to evaluate neuronal/glial damage, activation, and polarization. Apoptosis was assessed by TUNEL staining. Oxidative stress markers and electron microscopy were used to examine central oxidative stress and neuroinflammation. Results Respiratory Phenotype: Intermittent hypoxia (IH) led to an increased spontaneous apnea index in rats. Neuroinflammation: Microglia and astrocytes showed marked activation, demonstrated by hypertrophy, thickened branches, and an increased cell count. Neuronal Injury: Neurons in the preBötzinger complex (preBötC) were damaged, as shown by a decrease in Nissl-positive cells and electron microscopic observations of mitochondrial swelling and vacuolization. Oxidative Stress: This was evidenced by elevated NADPH oxidase activity and ROS levels, suggesting suppressed antioxidant enzyme activity and accumulated oxidative stress products. Conclusion The progressive nature of sleep apnea may be driven by intermittent hypoxia, which disrupts respiratory control by injuring the preBötzinger complex through microglia-mediated neuroinflammation. Support (if any)