3.5 Ferroptosis and obstructive sleep apnea
Obstructive sleep apnea (OSA) has been associated with acute ischemic stroke, hypertension, and atrial fibrillation117 . OSA is considered an independent risk factor for recurrent stroke118 . Its main pathophysiological feature is chronic intermittent hypoxia (CIH)9.
Intermittent hypoxia(IH) can induce ROS increase, lead to GSH depletion through endoplasmic reticulum stress and affect GPX4 activity119. Other studies have found that the levels of Nrf2-ARE path-related antioxidant enzyme GPX4 in the peripheral blood of patients with moderate to severe OSA are significantly reduced, affecting the antioxidant capacity of the central nervous system, resulting in an imbalance between oxidation and antioxidant, and ultimately leading to neuron damage and signal transduction abnormalities120. Other studies have confirmed that Nrf2 plays a protective role in the process of ferroptosis induced by IH9,121. This suggests that IH may affect the expression of the antioxidant protein in the Nrf2-ARE pathway, resulting in decreased expression of GPX4 and GSH in brain tissue, decreased antioxidant capacity, increased expression of ROS and MDA, and lipid peroxidation. In addition, elevated extracellular glutamate levels were found in the brains of OSA patients122,123. The abnormal increase of extracellular glutamate level may lead to the dysfunction of System Xc− transport, further inhibit the synthesis of GSH, affect the ability to resist lipid peroxidation and promote ferroptosis. Therefore, it can be inferred that ferroptosis may play an important role in OSA-induced brain injury, and the mechanism may be related to lipid peroxidation, abnormal increase of glutamate level, and Nrf2 regulation disorder. However, there is still a lack of research on OSA-mediated ferroptosis to promote the occurrence and progression of AIS, which still has great potential.