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Bexarotene Reduces Blood-Brain Barrier Permeability in Cerebral Ischemia-Reperfusion Injured Rats.

Authors :
Xu, Lu
Cao, Fang
Xu, Feng
He, Baicheng
Dong, Zhi
Source :
PLoS ONE. Apr2015, Vol. 10 Issue 4, p1-14. 14p.
Publication Year :
2015

Abstract

Background: Matrix metalloproteinase-9 (MMP-9) over-expression disrupts the blood-brain barrier (BBB) in the ischemic brain. The retinoid X receptor agonist bexarotene suppresses MMP-9 expression in endothelial cells and displays neuroprotective effects. Therefore, we hypothesized that bexarotene may have a beneficial effect on I/R-induced BBB dysfunction. Methods: A total of 180 rats were randomized into three groups (n = 60 each): (i) a sham-operation group, (ii) a cerebral ischemia-reperfusion (I/R) group, and (iii) an I/R+bexarotene group. Brain water content was measured by the dry wet weight method. BBB permeability was analyzed by Evans Blue staining and the magnetic resonance imaging contrast agent Omniscan. MMP-9 mRNA expression, protein expression, and activity were assessed by reverse transcription polymerase chain reaction, Western blotting, and gelatin zymography, respectively. Apolipoprotein E (apoE), claudin-5, and occludin expression were analyzed by Western blotting. Results: After 24 h, 48 h, and 72 h post-I/R, several effects were observed with bexarotene administration: (i) brain water content and BBB permeability were significantly reduced; (ii) MMP-9 mRNA and protein expression as well as activity were significantly decreased; (iii) claudin-5 and occludin expression were significantly increased; and (iv) apoE expression was significantly increased. Conclusions: Bexarotene decreases BBB permeability in rats with cerebral I/R injury. This effect may be due in part to bexarotene’s upregulation of apoE expression, which has been previously shown to reduce BBB permeability through suppressing MMP-9-mediated degradation of the tight junction proteins claudin-5 and occludin. This work offers insight to aid future development of therapeutic agents for cerebral I/R injury in human patients. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
19326203
Volume :
10
Issue :
4
Database :
Academic Search Index
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
102402720
Full Text :
https://doi.org/10.1371/journal.pone.0122744