Neuroprotective effect of bicyclol in rat ischemic stroke: down-regulates TLR4, TLR9, TRAF6, NF-κB, MMP-9 and up-regulates claudin-5 expression.

Abstract

BACKGROUND:

Inflammatory damage aggravates the cerebral ischemic pathological process and may pave a new way for treatment. Bicyclol has been proved to elicit a series of biologic effects through its anti-inflammatory property in treating hepatitis and hepatic ischemic/reperfusion injury. Whether this protective effect applies to cerebral ischemic injury, we therefore investigated the potential neuroprotective role of bicyclol and the underlying mechanisms.

METHODS:

Male Sprague-Dawley rats were randomly assigned to five groups: permanent middle cerebral artery occlusion (pMCAO), Vehicle (pMCAO+0.5% sodium carboxymethylcellulose), By-L (Vehicle+bicyclol 50 mg/kg), By-H (Vehicle+bicyclol 100 mg/kg) and Sham operated group. Bicyclol was administered intragastrically once a day for 3 days, after 1h of bicyclol pretreatment on the third day; rat brain ischemia was induced by pMCAO. Neurological deficit, infarct volume, and brain edema were measured at 24 h after stroke. Immunohistochemistry, Western blot and real-time quantitative PCR were used to detect the expression of TLR4, TLR9, TRAF6, NF-κB and MMP-9, claudin-5.

RESULTS:

Compared with pMCAO group, bicyclol significantly ameliorated neurological deficit, decreased infarct volume and edema, and down-regulated the expression of TLR4, TLR9, TRAF6, NF-κB and MMP-9 (P<0.05). Meanwhile, the expression of claudin-5 was increased (P<0.05).

CONCLUSIONS:

Bicyclol has neuroprotective effect on cerebral ischemia, and this protection may be through down-regulating TLR4, TLR9, TRAF6, NF-κB, MMP-9 and up-regulating claudin-5 expression.

• Authors: Jian Zhang, Baosheng Fu, Xiangjian Zhang, Linyu Chen, Lan Zhang, Xumeng Zhao, Xue Bai, Chunhua Zhu, Lili Cui, Lina Wang
• Journal: Brain research (Brain Res) Vol. 1528 Pg. 80-8 (Aug 28 2013) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 23850770 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Biphenyl Compounds
• Claudin-5
• Cldn5 protein, rat
• NF-kappa B
• Neuroprotective Agents
• TNF Receptor-Associated Factor 6
• Tlr4 protein, rat
• Tlr9 protein, rat
• Toll-Like Receptor 4
• Toll-Like Receptor 9
• bicyclol
• Matrix Metalloproteinase 9

Topics

• Animals
• Biphenyl Compounds (pharmacology)
• Brain (drug effects, pathology)
• Claudin-5 (metabolism)
• Down-Regulation
• Infarction, Middle Cerebral Artery (metabolism, pathology)
• Male
• Matrix Metalloproteinase 9 (metabolism)
• NF-kappa B (metabolism)
• Neuroprotective Agents (pharmacology)
• Rats
• Rats, Sprague-Dawley
• TNF Receptor-Associated Factor 6 (metabolism)
• Toll-Like Receptor 4 (metabolism)
• Toll-Like Receptor 9 (metabolism)
• Up-Regulation