Adenoviral Vector-Induced Silencing of RGMa Attenuates Blood-Brain Barrier Dysfunction in a Rat Model of MCAO/Reperfusion

Publication date: Available online 20 June 2018
Source:Brain Research Bulletin
Author(s): Min Li, Yuetao Wen, Rongrong Zhang, Fei Xie, Gang Zhang, Xinyue Qin
BackgroundRepulsive guidance molecule A (RGMa) is implicated in focal cerebral ischemia-reperfusion (I/R) injury, but its mechanisms are still largely unknown. This work focused on the effects of RGMa on the blood-brain barrier (BBB) after focal cerebral I/R injury.MethodsSprague-Dawley (SD) rats were randomly divided into four groups: sham, middle cerebral artery occlusion (MCAO)/reperfusion (I/R), MCAO/reperfusion administered recombinant adenovirus expressing sh-con (I/R + sh-con) and MCAO/reperfusion administered recombinant adenovirus expressing sh-RGMa (I/R + sh-RGMa) groups. Infarct volume, brain edema and neurological scores were evaluated at 3 day after reperfusion. Evens blue leakage and transmission electron microscopy was performed. And the expression level of claudin-5 and ZO-1, CDC-42 and PAK-1, RGMa were detected by western blot.ResultsCompared with I/R or I/R + sh-con groups, I/R + sh-RGMa group showed smaller infarction volume, attenuated brain edema, improved neurological scores and better BBB integrity, such as reduced Evans blue leakage and ultra-structural change. We also observed improved BBB function followed by down-regulation of MMP-9 and up-regulation of claudin-5 and ZO-1 in the I/R + sh-RGMa group. In addition, up-regulation of the CDC-42 and PAK-1 in the I/R + sh-RGMa group was obtained.ConclusionsRGMa may be involved in I/R injury associated with BBB dysfunction via the CDC-42/PAK-1 signal pathway and may be a promising therapeutic target for I/R injury.



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