Antioxidants and the risk of stroke: results from NHANES and two-sample Mendelian randomization study.

BACKGROUND: Stroke is the second leading cause of death worldwide, and observational studies have suggested a correlation between antioxidants and reduced stroke risk. However, it remains unclear whether causal relationships exist. METHODS: This study first performed a cross-sectional study of the association between the Composite Dietary Antioxidant Index (CDAI) and stroke using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Second, a two-sample univariable Mendelian Randomization (MR) was performed to analyze the causal effect of circulating levels of antioxidants on different subtypes of stroke. RESULTS: The cross-sectional study included a total of 24,892 participants representing more than 200 million US non-institutionalized residents, a multivariable logistic regression model revealed that the risk of stroke decreased by 3.4% for each unit increase in CDAI (P = 0.017), with a non-linear association found, indicating a reduction in stroke risk before an inflection point of 3.078. MR analysis revealed that genetically determined levels of retinol had a suggestive protective effect on subarachnoid hemorrhage (SAH) (OR = 0.348, P = 0.025), and genetically determined levels of selenium had a suggestive protective effect against SAH (OR = 0.826, P = 0.007). However, no causal relationship was found between antioxidants and ischemic stroke or intracranial hemorrhage risk. CONCLUSIONS: Evidence suggests that diet-derived antioxidants may reduce the risk of stroke, as indicated by the protective effects of retinol and selenium against SAH. However, more research is needed to fully understand how antioxidants prevent stroke.

Recent advances in the development of neuroprotective agents and therapeutic targets in the treatment of cerebral ischemia.

Stroke is a central nervous system disease that seriously affects people's quality of life and has the second highest rate of morbidity and mortality in the world. At present, clinical treatment strategies for acute ischemic stroke are mainly thrombolytic and thrombectomy therapy. However, these strategies are not able to protect patients from ischemic injuries. Therefore, treatment should further focus on methods that improve the survival rate of neurons around the ischemic area and neurological function. This article reviews current research and developments regarding small molecular compounds, including natural products and newly synthesized compounds that have neuroprotective effects and potential molecular targets for the recovery of post-ischemic stroke neural function that have been identified through lab investigations conducted during the last five years. Although pre-clinical studies of these compounds may not be immediately successful, current findings suggest that these therapeutic targets and neuroprotective agents are promising.