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Background: Cerebral white matter hyperintensity (WMH) is a pivotal imaging feature of cerebral small vessel disease (CSVD), closely correlated with an elevated risk of ischemic stroke (IS). Trimethylamine N-oxide (TMAO), a metabolite of gut microbiota, is increasingly associated with IS and atherosclerosis. However, the intricate relationship between TMAO and WMH remains ambiguous. This study aimed to study the connection between plasma TMAO and WMH. Furthermore, it assessed the potential of TMAO as a risk evaluation instrument for WMH., Methods: In this cross-sectional study, we categorized WMH into periventricular WMH (P-WMH) and deep WMH (D-WMH), based on its locations. The severity of WMH was assessed and grouped according to the Fazekas scale. Plasma TMAO levels were quantitatively determined. We established the correlation between plasma TMAO levels and WMH severity using a Logistic regression model. Additionally, we employed ROC curves to evaluate the diagnostic efficacy of plasma TMAO concentration in distinguishing the severity of WMH., Results: A higher plasma TMAO tertile was significantly linked to a higher Fazekas score, encompassing the overall score, P-WMH score, and D-WMH score ( p  < 0.001). A logical regression analysis revealed that plasma TMAO levels were independently associated with overall moderate and severe WMH, compared to overall non-mild WMH, in the unadjusted model (OR = 1.373, 95%CI 1.183-1.594 for moderate; OR = 1.384, 95%CI 1.192-1.607 for severe), the adjusted model a (OR = 1.436, 95%CI 1.214-1.669 for moderate; OR = 1.446, 95%CI 1.222-1.711 for severe) and the adjusted model b (OR = 1.490, 95%CI 1.234-1.800 for moderate; OR = 1.494, 95%CI 1.237-1.805 for severe). The analysis also showed an independent correlation between plasma TMAO levels and WMH severity, irrespective of the unadjusted model, adjusted model a, or adjusted model b, when considering P-WMH and D-WMH severity. The ROC indicated that, in overall WMH and P-WMH, the area under curve (AUC) for non-mild and severe WMH were both>0.5, while the AUC for moderate WMH was<0.5. In contrast, in D-WMH, the AUC for non-mild, moderate, and severe WMH were all>0.5., Conclusion: Plasma TMAO levels exhibited a significant correlation with both overall and region-specific WMH severity. Furthermore, the plasma TMAO levels displayed robust predictive capability for D-WMH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ji, Zhang, Zhang, Niu, Xiao, Chen and Qu.)

Background: Hypertension is a leading risk factor for cerebral small vessel disease (CSVD), a brain microvessels dysfunction accompanied by white matter lesions (WML). Trimethylamine N-oxide (TMAO), a metabolite of intestinal flora, is correlated with cardiovascular and aging diseases. Here, we explored the effect of TMAO on the demyelination of WML., Methods: Spontaneous hypertension rats (SHRs) and primary oligodendrocytes were used to explore the effect of TMAO on demyelination in vivo and in vitro . T2-weighted magnetic resonance imaging (MRI) was applied to characterize the white matter hyperintensities (WMH) in rats. TMAO level was evaluated using LC-MS/MS assay. The histopathological changes of corpus callosum were measured by hematoxylin-eosin and luxol fast blue staining. And the related markers were detected by IHC, IF and western blot assay. Mito Tracker Red probe, DCFH-DA assay, flow cytometry based on JC-1 staining and Annexin V-FITC/PI double staining were conducted to evaluate the mitochondrial function, intracellular ROS levels and cell apoptosis., Results: SHRs exhibited stronger WMH signals and a higher TMAO level than age-matched normotensive Wistar-kyoto rats (WKY). The corpus callosum region of SHR showed decreased volumes and enhanced demyelination when treated with TMAO. Furthermore, TMAO significantly elevated ROS production and induced NLRP3 inflammasome and impairment of mitochondrial function of oligodendrocytes. More importantly, TMAO enhanced the pyroptosis-related inflammatory death of oligodendrocytes., Conclusion: TMAO could cross the blood-brain barrier (BBB) and promote oligodendrocytes pyroptosis via ROS/NLRP3 inflammasome signaling and mitochondrial dysfunction to promote demyelination, revealing a new diagnostic marker for WML under hypertension., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ji, Tian, Niu, Yao and Qu.)

Biomarkers are objectively measured biological properties of normal and pathological processes. Early neurological deterioration (END) refers to the deterioration of neurological function in a short time after the onset of acute ischemic stroke (AIS) and is associated with adverse outcomes. Although multiple biomarkers have been found to predict END, there are currently no suitable biomarkers to be applied in routine stroke care. According to the Preferred Reporting Items for Systematic Review standards, we present a systematic review, concentrating on body fluids biomarkers that have shown potential to be transferred into clinical practice. We also describe newly reported body fluids biomarkers that can supply different insights into the mechanism of END. In our review, 40 scientific papers were included. Depending on the various mechanisms, sources or physicochemical characteristics of body fluids biomarkers, we classified related biomarkers as inflammation, protease, coagulation, metabolism, oxidative stress, and excitatory neurotoxicity. The body fluids biomarkers whose related articles are limited or mechanisms are unknown are categorized as other biomarkers. The inflammation-related biomarkers, such as neutrophil-to-lymphocyte ratio and hypersensitive C-reactive protein, play a crucial role among the mentioned biomarkers. Considering the vast heterogeneity of stroke progression, using a single body fluids biomarker may not accurately predict the risk of stroke progression, and it is necessary to combine multiple biomarkers (panels, scores, or indices) to improve their capacity to estimate END., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ji, Tian, Yao, Han, Niu and Qu.)