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Post-ischemia treatment with phenothiazine drugs [combined chlorpromazine and promethazine (C+P)] has been shown to be neuroprotective in stroke. The present study determined the effect of C+P in BBB integrity. Sprague-Dawley rats were divided into the following groups ( n=8 each): (1) stroke, (2) stroke treated by C+P with temperature control, and (3) stroke treated by C+P without temperature control. Infarct volume and neurological deficits were measured to assess the neuroprotective effect of C+P. BBB permeability was determined by brain edema and Evans blue leakage. Expression of BBB integral molecules, including proteins of aquaporin-4 and -9 (AQP-4, AQP-9), matrix metalloproteinase-2 and -9 (MMP-2, MMP-9), zonula occludens-1 (ZO-1), claudin-1\/5, occludin, and laminin were determined by Western blot. Stroke caused brain infarction and neurological deficits, as well as BBB damage, which were all attenuated by C+P through drug-induced hypothermia. When the reduced temperature was controlled to physiological levels, C+P still conferred neuroprotection, suggesting a therapeutic effect independent of hypothermia. Furthermore, C+P significantly attenuated the increase in AQP-4, AQP-9, MMP-2, and MMP-9 levels after stroke, and reversed the decrease in tight junction protein (ZO-1, claudin-1\/5, occludin) and basal laminar protein (laminin) levels. This study clearly indicates a beneficial effect of C+P on BBB integrity after stroke, which may be independent of drug-induced hypothermia. These findings further prove the clinical target and cell-signal communication of C+P treatment, which may direct us closer toward the development of an efficacious neuroprotective therapy.<\/jats:p>","DOI":"10.1177\/0963689718819443","type":"journal-article","created":{"date-parts":[[2018,12,20]],"date-time":"2018-12-20T05:17:08Z","timestamp":1545283028000},"page":"145-156","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":39,"title":["Therapeutic Target and Cell-signal Communication of Chlorpromazine and Promethazine in Attenuating Blood\u2013Brain Barrier Disruption after Ischemic Stroke"],"prefix":"10.1177","volume":"28","author":[{"given":"Fengwu","family":"Li","sequence":"first","affiliation":[{"name":"China-America Institute of Neuroscience, Luhe Hospital, Capital Medical University, Beijing, 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