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Advanced Neurology TMAO and stroke

of IL-6 and TNF-α. TNF-α is one of the key cytokines according to a meta-analysis covering a sizable sample.
involved in the destruction of the blood–brain barrier. Therefore, regulating TMAO concentration in circulation
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The level of inflammation after stroke is closely related may serve as a new intervention and treatment for
to the functional prognosis of stroke. Higher levels of hypertension, making the study of the correlation between
inflammation often lead to poor prognosis for stroke. As hypertension and TMA/TMAO highly important.
mentioned above, TMAO induces various inflammatory Recent research has shown that TMAO has no effect on
factors, which stimulate each other’s expression, triggering the blood pressure of normotensive animals, although it is
a vicious cycle and leading to a sustained inflammatory known for its function to sustain blood pressure increase
response. In addition, a dose-response meta-analysis of associated with angiotensin II (Ang II). It has been reported
the association between TMAO levels and inflammation that TMAO promotes Ang II-induced vasoconstriction
revealed a non-linear relationship between elevated through the protein kinase r-like endoplasmic reticulum
TMAO concentrations and elevated C-reactive protein kinase (PERK)/reactive oxygen species/calmodulin-
concentrations. Therefore, we speculate that the dependent protein kinase/phospholipase cβ3 axis, thereby
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inflammatory response elicited by TMAO not only prolonging the hypertensive effect induced by Ang II.
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facilitates atherosclerosis but also exacerbates injury after Another recent research found that serum TMAO content
IS, providing a potential indicator for predicting prognosis
and guiding treatment. is associated with the odds of developing the first stroke
in people with hypertension, underlining the significance
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6. Improved platelet activity of studying the relationship between TMAO and cardiac
stroke. In recent years, the incidence of cardiac embolism
TMAO raises the risk of thrombosis and platelet in IS patients has risen significantly, and strokes caused by
hyperreactivity. By stimulating the release of intracellular this condition have also become more severe than those
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Ca , TMAO can directly enhance platelet binding to caused by other stroke subtypes. The risk of developing
2+
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various agonists, increasing platelet adhesion, aggregation, an IS caused by atrial fibrillation is positively correlated
and production. Activated platelets release numerous with TMAO concentrations. At the same time, TMAO
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inflammatory mediators locally; support leucocyte can also increase the incidence of atrial fibrillation. In
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chemotaxis, adhesion, and migration to the inflammatory summary, these findings portray elevated TMAO levels
site; and promote thrombosis. The occurrence of acute as a factor of not only hypertension but also IS, including
stroke is closely linked to thrombosis formation. An cardioembolic stroke. Therefore, studying TMAO and
in vitro study on vascular endothelial cell cultures showed its metabolic pathways may offer new insights for the
that adding TMAO to the culture medium can increase prevention and treatment of hypertension and IS.
tissue factor (TF) expression. The TF pathway is the rate-
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limiting step in thrombosis within the body. According 8. Interventions and prospects of TMAO
to recent investigations, endothelial TF can be precisely
inhibited by targeting the non-lethal suppression of Based on the primary risk factors for stroke, the main
intestine microbial choline TMA lyase, which has been interventions proposed to forestall the development of
shown to contribute to the production of TMAO-related stroke include smoking cessation, blood pressure control,
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thrombosis. However, acute TMAO treatment showed and a healthy diet. Measures to prevent cerebrovascular
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no effect on stroke size or endothelial function in a rat disease through lifestyle changes obviously stand as the
study, which failed to afford a clear picture of the complex first choice. Existing studies have demonstrated that
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relationship between TMAO and thrombosis; therefore, human interventions to regulate TMAO production can
further research on this relationship is essential. reduce the severity of atherosclerosis and the likelihood
of thrombosis in animal models. Although the specific
7. TMAO and hypertension effective measures for inhibiting TMAO levels have not
yet been identified, several methods that hold potential to
TMA, TMA-producing bacteria, and TMAO are connected
to hypertension in multiple facets. A potential treatment reduce circulatory TMAO levels, such as dietary and drug
strategy for hypertension might include targeting TMA- interventions, have been recommended in a few studies.
producing bacteria/TMA/TMAO pathways. In addition, Changes in eating habits exert an impact on TMAO
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a noteworthy positive dose-dependent association has levels. A study revealed that a diet rich in red meat can
been shown between the risk of hypertension and the raise circulatory TMAO levels, which can be reduced
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circulating TMAO concentration. Individuals with high within 4 weeks by stopping red meat intake. The study
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TMAO concentrations are more likely than those with confirmed that limiting red meat intake and following a
low TMAO concentrations to experience hypertension, Mediterranean diet is beneficial for primary prevention in

Volume 3 Issue 3 (2024) 4 doi: 10.36922/an.3005