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Sac-1004, a vascular leakage blocker, reduces cerebral ischemia—reperfusion injury by suppressing blood–brain barrier disruption and inflammation

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Authors
Zhang, Haiying; Park, Joon Ha; Maharjan, Sony; Park, Jeong Ae; Choi, Kyu-Sung; Park, Hyojin; Jeong, Yoonjeong; Ahn, Ji Hyeon; Kim, In Hye; Lee, Jae-Chul; Cho, Jeong Hwi; Lee, In-Kyu; Lee, Choong Hyun; Hwang, In Koo; Kim, Young-Myeong; Suh, Young-Ger; Won, Moo-Ho; Kwon, Young-Guen
Issue Date
2017-06-23
Publisher
BioMed Central
Citation
Journal of Neuroinflammation, 14(1):122
Keywords
Sac-1004Cerebral ischemiaBlood–brain barrierTight junctionInflammationNeuroprotection
Abstract
Background
Blood–brain barrier (BBB) breakdown and inflammation are critical events in ischemic stroke, contributing to aggravated brain damage. The BBB mainly consists of microvascular endothelial cells sealed by tight junctions to protect the brain from blood-borne substances. Thus, the maintenance of BBB integrity may be a potential target for neuroprotection. Sac-1004, a pseudo-sugar derivative of cholesterol, enhances the endothelial barrier by the stabilization of the cortical actin ring.

Results
Here, we report on the protective effects of Sac-1004 on cerebral ischemia-reperfusion (I/R) injury. Treatment with Sac-1004 significantly blocked the interleukin-1β-induced monolayer hyperpermeability of human brain microvascular endothelial cells (HBMECs), loss of tight junctions, and formation of actin stress fiber. Sac-1004 suppressed the expression of adhesion molecules, adhesion of U937 cells, and activation of nuclear factor-κB in HBMECs. Using a rat model of transient focal cerebral ischemia, it was shown that Sac-1004 effectively ameliorated neurological deficits and ischemic damage. In addition, Sac-1004 decreased BBB leakage and rescued tight junction-related proteins. Moreover, the staining of CD11b and glial fibrillary acidic protein showed that Sac-1004 inhibited glial activation.

Conclusions
Taken together, these results demonstrate that Sac-1004 has neuroprotective activities through maintaining BBB integrity, suggesting that it is a great therapeutic candidate for stroke.
Language
English
URI
https://doi.org/10.1186/s12974-017-0897-3

http://hdl.handle.net/10371/117764
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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