Jeong Hun Lee1, Soonmi Won2, Donald G Stein3. 1. Department of Emergency Medicine, Dongguk University School of Medicine, Goyang-si, Gyeonggi-do, Republic of Korea. 2. Department of Emergency Medicine Brain Research Laboratory, Emory University, Atlanta, GA, USA. 3. Department of Emergency Medicine Brain Research Laboratory, Emory University, Atlanta, GA, USA. Electronic address: dstei04@emory.edu.
Abstract
UNLABELLED: This study examines the effects of progesterone on blood-brain barrier (BBB) integrity following thrombin administration. Thrombin is expressed in many diseases which affect neural tissue and is associated with breakdown of the BBB. Progesterone has shown protective effects on the BBB in stroke and traumatic brain injury. METHODS: Mouse brain endothelial (bEnd.3) cells were treated with progesterone (20 μmol/l) for 24h before thrombin administration (60 U/ml). BBB permeability was measured by transendothelial electrical resistance (TEER), because TEER decrease is associated with BBB compromise. Tight junction (TJ) proteins (occludin, claudin-5, and zonula occludens-1) and endothelial protein C receptor (EPCR) were analyzed. RESULTS: Thrombin decreased TEER and progesterone prevented that decrease. TJ proteins and EPCR were also decreased after thrombin treatment and progesterone treatment blocked that effect. CONCLUSION: Progesterone can attenuate thrombin-induced BBB disruption by blocking the degradation of TJ proteins and EPCR in bEnd.3 cells.
UNLABELLED: This study examines the effects of progesterone on blood-brain barrier (BBB) integrity following thrombin administration. Thrombin is expressed in many diseases which affect neural tissue and is associated with breakdown of the BBB. Progesterone has shown protective effects on the BBB in stroke and traumatic brain injury. METHODS:Mouse brain endothelial (bEnd.3) cells were treated with progesterone (20 μmol/l) for 24h before thrombin administration (60 U/ml). BBB permeability was measured by transendothelial electrical resistance (TEER), because TEER decrease is associated with BBB compromise. Tight junction (TJ) proteins (occludin, claudin-5, and zonula occludens-1) and endothelial protein C receptor (EPCR) were analyzed. RESULTS:Thrombin decreased TEER and progesterone prevented that decrease. TJ proteins and EPCR were also decreased after thrombin treatment and progesterone treatment blocked that effect. CONCLUSION:Progesterone can attenuate thrombin-induced BBB disruption by blocking the degradation of TJ proteins and EPCR in bEnd.3 cells.
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