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.