Low ambient temperature exposure increases the risk of ischemic stroke by promoting platelet activation

Accumulating epidemiological evidence suggests the association between low ambient temperature exposure and the risk of ischemic stroke, but the underlying mechanisms remain unclear.Given the crucial role of platelet activation and thrombosis in ischemic stroke, this study aims to investigate the effect of ambient temperature on platelet activation through multi-center clinical data in Tianjin as well as animal experiments.From 2018 to 2020, nearly 3000 ischemic stroke patients from three stroke centers in Tianjin were included in the analysis, among them the ADP induced platelet aggregation rate was available. Meteorological data from the same period had also been collected. After controlling for confounding factors, the generalized additive mixed model (GAMM) was used to evaluate the correlation between environmental temperature and platelet aggregation rate. In further animal experiments, platelet function assessments were conducted on mice from the cold exposure group and the normal temperature group, including platelet aggregation, spreading, and clot retraction. Additionally, tail bleeding and mesentery thrombosis were also tested to monitor hemostasis and thrombosis in vivo.A nonlinear "S" shaped relationship between outdoor temperature and platelet aggregation was found. Each 1 °C decrease of mean temperature was associated with an increase of 7.77 % (95 % CI: 2.06 % - 13.48 %) in platelet aggregation. The ambient temperature is not related to other platelet parameters. Subgroup analysis found that males, people aged ≥65 years, and hypertensive individuals are more susceptible to temperature changes. Furthermore, animal experiments demonstrated that the increased CIRBP levels and subsequent activation of p-AKT/p-ERK may be one of the reasons for cold exposure induced platelets activation.Both clinical data and basic research support that low ambient temperature exposure has the potential to increase platelet activation. These results provide a basis for understanding the potential mechanism of temperature variations on the pathogenesis of cerebrovascular diseases.