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However, whether PFO closure was effective in improving NCDEMs and the mechanism were unclear. Twenty\u2010eight patients with migraine or epilepsy who underwent PFO closure were recruited. Notably, approximately half of patients received 50% or more reduction in seizure or headache attacks. Meanwhile, the postoperative blood oxygen partial pressure and oxygen saturation were elevated after PFO closure. Multisite (peripheral, right, and left atrial) and multitimepoint (before and after surgery) plasma proteomics from patients showed that the levels of free hemoglobin and cell adhesion molecules (CAMs) were significantly increased after PFO closure, which may be related to the relief of the hypoxic state. Furtherly, the omics data from multiple brain regions of mice revealed that a large number of proteins were differentially expressed in the occipital region in response to PFO, including redox molecules and CAMs, suggesting PFO\u2010caused hypoxia may have great impacts on occipital region. Collectively, PFO may cause NCDEMs due to RLS\u2010induced hypoxia, and PFO closure could prevent RLS to improve migraine and epilepsy.<\/jats:p>","DOI":"10.1002\/mco2.334","type":"journal-article","created":{"date-parts":[[2023,8,12]],"date-time":"2023-08-12T07:20:16Z","timestamp":1691824816000},"source":"Crossref","is-referenced-by-count":12,"title":["Multisite and multitimepoint proteomics reveal that patent foramen ovale closure improves migraine and epilepsy by reducing right\u2010to\u2010left shunt\u2010induced hypoxia"],"prefix":"10.1002","volume":"4","author":[{"given":"Bosi","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Neurology West China Hospital Sichuan University Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy National Clinical Research Center for Geriatrics and Department of General Practice West China 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