The present study is the first to suggest the eosinophil is a dynamic variable, and its variation is associate with large infarct volume and poor outcome.
A growing body of evidence suggests that inflammatory responses after a stroke might continuously shape the evolving pathology and affect the patients' long-term clinical outcome. In previous studies, a high NLR12, high-sensitive C-reactive protein13 and lipoprotein-associated phospholipase A214 and a low eosinophil count10 were found to be associated with poor prognosis in ischemic stroke patents. In addition, the NLR and eosinophil were associated with infarct volume5, 6 and higher infection rate after a stroke occur10. However, all of these studies mostly focused on static value at baseline, which probably not reflect the complicated dynamic changes of the patients’ conditions. Recent studies showed that NLR measured at admission before any treatment was not predictive of poor functional outcome after endovascular treatment8, 15, but NLR obtained at day 1 was independently associated with a worse outcome at 3 months. Our results were consistent with previous studies that have demonstrated this correlation between NLR at day 1 and a poor prognosis in patients with AIS. We first studied the relationship between dynamic change of eosinophil and acute ischemic stroke. Conclusion similar with the NLR, the eosinophil obtained at day 1 not at admission was independently associated with a worse outcome. We also found that compared with NLR and eosinophil measured at day 1, increased NLR and decreased eosinophils from admission to the next day were more meaningful after adjustment for potential confounders. By reading lots of literatures, there might be some interesting conclusions we observed. In two prospective cohort studies showed that increased eosinophils were independent predictors of cardiovascular and cerebrovascular events16, 17. However, in most retrospective studies demonstrated that eosinopenia was associated with worse clinical outcomes in patients with cardiac-cerebral vascular events9, 10, 18, 19. These different results may be due to differences in the timing of blood sample obtained and in the distribution of eosinophil in different stages of diseases. We may conjecture that healthy people with elevated eosinophil counts increase the risk of stroke as eosinophil can promote thrombosis and induce unstable plaque20, 21, once those people suffer a stroke a large number of eosinophils sharply declined and lead to poor prognosis through a number of mechanisms.
The mechanisms underlying these observations remain unclear. Acute stress can lead to eosinopenia by stimulating the release of adrenal glucocorticosteroids and epinephrine 22, 23. Patients with large infarct volume may be more likely to activate the stress responses which may partly explained why those people were often accompanied by eosinopenia. Nevertheless, a sharply reduction in peripheral blood eosinophils does not only seem to be a result of adrenal mediation, because this was also observed in adrenalectomized rabbits 22. Many researches proved that chemotactic factors such as complement 5a and fibrin fragments can mediate eosinophils migration to target organs or tissues, which may be one of the reason to drop the peripheral eosinophil count24, 25. Ping J et al. showed that eosinophil accumulation in the thrombus and decrease in peripheral blood in patients with acute coronary syndrome (ACS)26. Another research reported that eosinophils were increasingly detectable within the injured myocardium and eosinophil-deficient patients with acute myocardial infarction demonstrated worse cardiac function18, 27. In our study, we found that 31% of stroke patients with eosinopenia were classified as the cardioembolic subtype. This implied that eosinophils promote thrombus formation and growth and lead to massive cerebral infarction. There was a research had already proved that the more eosinophils infiltrated the greater thrombi size in patients with acute coronary syndrome28. Eosinopenia also be the result of degranulation which made eosinophils no longer be recognized in the circulation29. Eosinophil granule proteins, including eosinophil cationic protein, eosinophil peroxidase, and major basic protein can cause cytotoxic protein-mediated thrombosis and endothelial injury 30. ECP also stimulates fibroblast migration and fibrosis, which could be play an important role in the development of atherosclerosis31–34. It could be speculated that increased ECP and activated eosinophils were associated with increased incidence of AIS through effects on unstable plaque.
The main strength of our study is that we compared the variation of eosinophil in same patients at different time and found patients with eosinopenia were significantly associated with poor outcome, which may provide another pathway alongside thrombosis and lipid reduction to target for a decrease in the development of cerebral vascular diseases.
However, our findings also have some limitations. First, the sample size was small which could detract from the validity of the findings. Second, the kind and amount of inflammation factors changed over time. So as a dynamic index, the value of the eosinophil trajectory over time to predict AIS prognosis should be further explored. Future efforts should be directed to collect blood samples at more points to investigate the relationship between eosinophil and AIS. Finally, there was no researches reported eosinophils in thrombosis in AIS patients.