Administration of fingolimod before endovascular therapy arrests local leukocyte responses in acute ischemic stroke

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.