Overexpression of caveolin-1 attenuates brain edema by inhibiting tight junction degradation

// Kang-Ho Choi 1,2 , Hyung-Seok Kim 3,* , Man-Seok Park 2,* , Eun-Bin Lee 2,3 , Jung-Kil Lee 4 , Joon-Tae Kim 2 , Ja-Hae Kim 5 , Min-Cheol Lee 6 , Hong-Joon Lee 7 and Ki-Hyun Cho 2 1 Department of Neurology, Chonnam National University Hwasun Hospital, Hwasun, Korea 2 Department of Neurology, Chonnam National University Medical School, Gwangju, Korea 3 Department of Forensic Medicine, Chonnam National University Medical School, Gwangju, Korea 4 Department of Neurosurgery, Chonnam National University Medical School, Gwangju, Korea 5 Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, Korea 6 Department of Pathology, Chonnam National University Medical School, Gwangju, Korea 7 Medical Research Institute, Chungang University College of Medicine, Seoul, Korea * These authors have contributed equally to this work Correspondence to: Hyung-Seok Kim, email: // Man-Seok Park, email: // Keywords : caveolin, overexpression, cerebral edema, blood-brain barrier permeability, Pathology Section Received : May 10, 2016 Accepted : September 25, 2016 Published : September 29, 2016 Abstract Cerebral edema from the disruption of the blood-brain barrier (BBB) after cerebral ischemia is a major cause of morbidity and mortality as well as a common event in patients with stroke. Caveolins (Cavs) are thought to regulate BBB functions. Here, we report for the first time that Cav-1 overexpression (OE) decreased brain edema from BBB disruption following ischemic insult. Edema volumes and Cav-1 expression levels were measured following photothrombosis and middle cerebral artery occlusion (MCAO). Endothelial cells that were transduced with a Cav-1 lentiviral expression vector were transplanted into rats. BBB permeability was quantified with Evans blue extravasation. Edema volume was determined from measures of the extravasation area, brain water content, and average fluorescence intensity after Cy5.5 injections. Tight junction (TJ) protein expression was measured with immunoblotting. Cav-1 expression levels and vasogenic brain edema correlated strongly after ischemic insult. Cav-1 expression and BBB disruption peaked 3 d after the MCAO. In addition, intravenous administration of endothelial cells expressing Cav-1 effectively increased the Cav-1 levels 3 d after the MCAO ischemic insult. Importantly, Cav-1 OE ameliorated the vasogenic edema by inhibiting the degradation of TJ protein expression in the acute phase of ischemic stroke. These results suggested that Cav-1 OE protected the integrity of the BBB mainly by preventing the degradation of TJ proteins in rats. These findings need to be confirmed in a clinical setting in human subjects.