Administration of fingolimod before endovascular therapy arrests local leukocyte responses in acute ischemic stroke
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ABSTRACT
Features of lymphocytes exerted at the luminal side of the brain microvasculature remain unknown in acute human ischemic stroke. Here, we used an endovascular technique to aspirate local blood with a microcatheter placed distally to the occlusive clot before recanalization in patients undergoing endovascular therapy (EVT). By comparing patients treated with fingolimod (a lymphocyte inhibitor) or not prior to EVT, we provide direct evidence for lymphocyte influx to the ipsilateral brain microvasculature. First, we demonstrated that several types of lymphocytes reached the target territory via retrograde collateral flow, and that their counts locally were higher than in the peripheral circulation. Second, although stroke-induced immunodepression was apparent in the peripheral circulation, we found a time-dependent accumulation of lymphocytes in the occluded vascular compartment. Third, lymphocytes' invasion from the periphery into the local territory's cerebral circulation was clearly blocked by a 6-hour fingolimod intervention prior to recanalization treatment. This study, akin to fingolimod-modulated vascular-inflammation, paves a potential way for ultra-early treatment strategies before recanalization. -
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REFERENCES
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Yu X., Zhao W., Lin K., et al. (2026). Administration of fingolimod before endovascular therapy arrests local leukocyte responses in acute ischemic stroke. The Innovation Neurology 1:100010. https://doi.org/10.59717/j.tine.2026.100010
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Yu X., Zhao W., Lin K., et al. (2026). Administration of fingolimod before endovascular therapy arrests local leukocyte responses in acute ischemic stroke. The Innovation Neurology 1:100010. https://doi.org/10.59717/j.tine.2026.100010
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Figure 1.
Stroke-induced lymphocytes persistently influx to the local circulation of occluded vascular territory via retrograde collateral flow A, Gating strategy of flow cytometry; double negative T cells (DNT). B, Lymphocyte subtype comparison; data are given as median (top and bottom of the box indicate the interquartile; the error bar indicates the Minimum and Maximum); Wilcoxon matched-pairs signed rank test was used; Green dashed lines represent the lowest number of peripheral bloods from the controls without stroke (N = 5). C, Correlation analysis, Spearman’s correlation coefficients were used.
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Figure 2.
Receiving fingolimod at 6 hours prior to endovascular therapy adequately modulates lymphocytes-flux to the local circulation of occluded vascular territory A. Fingolimod interventional and sampling protocol. Patients who were transported by ambulance from hospital 1 to hospital 2 (thrombectomy-capable center), received oral fingolimod (0.5 mg Gilenya, Novartis) at hospital 1 about 6-hours preceding endovascular therapy. B. Receving fingolimod 6 hours before EVT arrests local leukocyte responses.
