Unknown

Dataset Information

0

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


ABSTRACT: 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.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-1?-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-?B 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.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.

SUBMITTER: Zhang H 

PROVIDER: S-EPMC5481915 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

altmetric image

Publications

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

Zhang Haiying H   Park Joon Ha JH   Maharjan Sony S   Park Jeong Ae JA   Choi Kyu-Sung KS   Park Hyojin H   Jeong Yoonjeong Y   Ahn Ji Hyeon JH   Kim In Hye IH   Lee Jae-Chul JC   Cho Jeong Hwi JH   Lee In-Kyu IK   Lee Choong Hyun CH   Hwang In Koo IK   Kim Young-Myeong YM   Suh Young-Ger YG   Won Moo-Ho MH   Kwon Young-Guen YG  

Journal of neuroinflammation 20170623 1


<h4>Background</h4>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 acti  ...[more]

Similar Datasets

| S-EPMC4405202 | biostudies-literature
| S-EPMC4132223 | biostudies-literature
| S-EPMC5112296 | biostudies-literature
| S-EPMC8471287 | biostudies-literature
| S-EPMC7211409 | biostudies-literature
| S-EPMC5585260 | biostudies-literature
| S-EPMC10496505 | biostudies-literature
| S-EPMC7653860 | biostudies-literature
| S-EPMC7175589 | biostudies-literature
| S-EPMC3323185 | biostudies-literature