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Despite the FDA recommendation of a 48-week treatment period for PPIs (2), nearly 7% of PPI users continue therapy for more than 3 years, surpassing the recommended FDA usage guidelines and increasing the propensity for adverse long-term effects (3, 4)

NO plays a critical role in maintaining vascular homeostasis, and its synthesis is primarily mediated by NOS enzymes

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Secondary injury refers to further molecular and chemical inflammatory reactions such as blood hemoglobin and iron release, dysfunction of brain metabolism and cerebral blood flow, further triggering neuroinflammatory processes, oxidative stress, glutamatergic excitotoxicity and mitochondrial dysfunction, etc., which cause further brain damage (Stocchetti et al., 2017)

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