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.

BackgroundHypertension 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.MethodsSpontaneous 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.ResultsSHRs 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.ConclusionTMAO 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.