{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T08:50:49Z","timestamp":1777366249470,"version":"3.51.4"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Ozonated autohemotherapy is a therapeutic method that utilizes the contact of medical ozone with blood to achieve the effect of ozone oxidative preconditioning, and then re-infuses it back into the human body. It has the functions of alleviating oxidative stress damage, reducing neuroexcitation toxicity, and mitigating cellular edema and inflammatory responses. Cerebral infarction has a significant social hazard, and there are multiple treatment methods available. There have been reports of treating cerebral infarction with ozonated autohemotherapy, but the efficacy and mechanism of action are not yet clear. The background now includes information about the proteins measured, specifically neuron-specific enolase (NSE) and S100\u03b2 protein, which are markers of neuronal cell damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A randomized controlled study was conducted, enrolling 62 patients with acute cerebral infarction to investigate the therapeutic effect of ozonated autohemotherapy on acute cerebral infarction. The study included three groups: a control group, an oxygen placebo group, and an ozone therapy group. The intervention was administered over a period of 5\u202fdays, with patients undergoing treatment within 24\u202fh of symptom onset. Inclusion criteria comprised patients diagnosed with acute cerebral infarction, aged &amp;gt;18\u202fyears, with an NIHSS score between 4 and 15. Exclusion criteria included other neurological disorders, severe infectious diseases, and contraindications for ozone therapy. The efficacy was primarily evaluated through neurological function scoring, motor function scoring, cognitive scoring, and the detection of neuron-specific enolase (NSE) and S100\u03b2 protein (A neurotrophic factor), which are markers of neuronal cell damage. The two genes involved in the study are HIF-1 and Nrf-2. The mechanism of ozonated autohemotherapy in treating acute cerebral infarction was also explored by detecting these two genes and three indicators related to oxidative stress in the body.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ozonated autohemotherapy significantly improved the prognosis of acute cerebral infarction, with NIHSS scores decreasing by 30%, Barthel Index scores increasing by 25%, and MoCA scores improving by 20% compared to the control group. Levels of NSE and S100-<jats:italic>\u03b2<\/jats:italic> protein were reduced by 25 and 30%, respectively, compared to baseline. In the ozone treatment group, superoxide dismutase (SOD) and malondial Dehyde (MDA) levels decreased, while glutathione peroxidase (GSH-Px) levels increased, and both HIF-1 and Nrf-2 levels were elevated compared to before. Moreover, it did not increase the risk of heart, liver, and kidney damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>It suggests that ozone may improve oxidative stress by regulating HIF-1 and Nrf-2, reduce the oxidative stress response and inflammatory damage caused by ischemia of neuronal cells in acute cerebral infarction, thereby improving neurological function and prognosis. The treatment method is safe in the short term. Long-term safety requires further research.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1595568","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T05:26:49Z","timestamp":1753421209000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["A clinical study on ozone autohemotherapy for the treatment of acute ischemic 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