Background and Purpose:
Eotaxin, a TH2 chemokine, has been shown to increase in mouse brain and plasma following experimental stroke. While eotaxin has been associated with age-related deficits in neurogenesis, little is known about its role in ischemic injury.
Hypothesis:
We tested the hypothesis that serum eotaxin levels are associated with long-term stroke outcome, with follow up mechanistic studies in a mouse model of ischemic stroke.
Methods:
Serum was taken from patients (n=158) 24 hours after ischemic stroke onset. Levels of serum eotaxin were quantified by ELISA, then analyzed for outcome association. For murine studies, animals (n=14) underwent 90-minute middle cerebral artery occlusion and were sacrificed at 24 hours, with sham surgery mice serving as controls. Blood was incubated with or without eotaxin (100 ng/ml) and stained for leukocyte markers and CD62L (L-selectin).
Results:
Although eotaxin protein levels were not significantly different between sexes, a multivariate analysis controlling for age, stroke severity and cardiovascular risk factors revealed a male-specific association between higher eotaxin levels at 24 hours post-stroke and a positive functional outcome at three months (p=.010). Analysis of peripheral leukocytes isolated from both sham and stroke mice revealed that addition of eotaxin to whole blood significantly increased the activation of myeloid cells in both in male (p=.0031) and female (p=.0048) animals, as measured by shedding of L-selectin. Further experiments demonstrated that shedding of L-selectin on CD8+ T-cells after treatment of whole blood with eotaxin was significant only in female animals (p=.0008).
Conclusion:
In conclusion, the results of this study suggest that eotaxin has a sex-specific association with improved stroke outcomes. Murine studies demonstrate that eotaxin causes activation of peripheral leukocytes (as measured by loss of L-selectin), with a sexually dimorphic effect on CD8+ T-cell activation that may alter the character of the post-stroke immune response and support a pro-recovery inflammatory phenotype in males. This research underscores the importance of studying both sexes in future ischemic inflammatory research.
Examination of Genetic Variants Revealed from a Rat Model of Brain Ischemia in Patients with Ischemic Stroke: A Pilot Study
