The advent of thrombectomy ushered in a new era of stroke therapy, extending the reperfusion window to 24 hours post-stroke occurrence. The evolving criteria for reperfusion eligibility suggest a growing inclusion of patients for such treatment. However, given the variable outcomes and responses to thrombectomy, there is a pressing need to reevaluate the understanding of the natural progression and connection between leukocyte recruitment and ischemia/reperfusion injury (I/RI) in stroke. Notable discrepancies have been observed between preclinical and clinical outcomes, underscoring the importance of revisiting foundational concepts. Prior research has highlighted the heterogeneity of reperfusion itself within preclinical models and identified an association between elevated polymorphonuclear (PMN) counts and unfavorable outcomes post-reperfusion. Efforts to restrict leukocyte migration yielded limited success in clinical trials, prompting the need to comprehensively define the spatiotemporal patterns of leukocyte infiltration in I/RI. This study focuses on disrupting recruitment and movement to investigate how altering leukocyte infiltration patterns might impact stroke volume.
The intricate recruitment of PMNs exhibits substantial spatiotemporal variations throughout infarcted stroke tissue during I/RI and can be influenced by PECAM antibody blockade. At early timepoints, cortical surface infiltration is prominent and expands through both the cortex and subcortex by 72 hours. PMNs constitute the primary leukocyte population in the ischemic hemisphere at 24 hours, with their numbers increasing over the 72-hour period alongside monocytes. PECAM blockade confines a significant portion of leukocytes to the cortex without altering their overall quantity, corroborating earlier findings of reduced stroke infarct size. PECAM disruption modifies PMN progression into infarcted tissue post-I/RI, suggesting that manipulating leukocyte infiltration patterns, rather than merely reducing total numbers, could have a protective effect on stroke. The research emphasizes new potential target to regulate leukocyte infiltration and improve outcomes, offering valuable insights into enhancing therapeutic strategies for ischemic stroke.