In the realm of neurointerventional treatment after ischemic stroke, ineffective reperfusion represents a significant challenge, with the integrity of the blood-brain barrier (BBB) serving as a pivotal determinant of outcomes. This review sheds light on the unique characteristics and roles of brain endothelial cells within the context of stroke with ineffective reperfusion. We address the distinctiveness of brain endothelial cells relative to their counterparts in different tissues, outlining their pathophysiological transformations, functional impairments, and inflammatory cascades post-stroke. The differential gene expression between brain endothelial cells and those from other organs provide a deeper understanding of their intrinsic roles in neuroprotective therapy. Looking ahead, exploring analogies between brain endothelial cells and those from organs with similar ischemia-reperfusion injury profiles could lead to innovative therapeutic strategies. This review highlights the paramount importance of understanding the nuanced roles of endothelial cells in mediating BBB dynamics, ultimately influencing reperfusion outcomes.