Baincalein alleviates early brain injury after experimental subarachnoid hemorrhage in rats: possible involvement of TLR4/NF-κB-mediated inflammatory pathway.

Abstract

Early brain injury (EBI) following subarachnoid hemorrhage (SAH) largely contributes to unfavorable outcomes. Hence, effective therapeutic strategies targeting on EBI have recently become a major goal in the treatment of SAH patients. Baicalein is a flavonoid that has been shown to offer neuroprotection in kinds of brain injury models. This study investigated the effects of baicalein on EBI in rats following SAH. SAH was inducted in male Sprauge-Dawley rats by injection of fresh non-heparinized arterial blood into the prechiasmatic cistern. Baicalein (30 or 100 mg/kg) or vehicle were administrated 30 min after injury. Neurological deficit, brain edema, blood-brain barrier (BBB) permeability and neural cell apoptosis were assessed. To explore the further mechanisms, the change of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) signaling pathway and the levels of apoptosis associated proteins were also examined. Our study showed that treatment with baicalein (30 mg/kg) significantly improved neurological function at 24h after SAH and reduced brain edema at both 24h and 72 h after SAH. Baicalein also significantly reduced neural cell death, BBB permeability. These changes were associated with the remarkable reductions of TLR4 expression, IκB-α degradation, NF-κB translocation to nucleus, as well as the expressions of matrix metalloproteinase-9, tight junctions protein, interleukin-1β and tumor necrosis factor- ɑ. These findings suggest that baicalein may ameliorate EBI after SAH potentially via inhibition of inflammation-related pathway.

• Authors: Chun-xi Wang, Guang-bin Xie, Chen-hui Zhou, Xiang-sheng Zhang, Tao Li, Jian-guo Xu, Ning Li, Ke Ding, Chun-hua Hang, Ji-xin Shi, Meng-liang Zhou
• Journal: Brain research (Brain Res) Vol. 1594 Pg. 245-55 (Jan 12 2015) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 25451085 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Flavanones
• NF-kappa B
• Neuroprotective Agents
• Tlr4 protein, rat
• Toll-Like Receptor 4
• baicalein

Topics

• Animals
• Blood-Brain Barrier (drug effects)
• Blotting, Western
• Brain Injuries (etiology, prevention & control)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Flavanones (pharmacology)
• In Situ Nick-End Labeling
• Inflammation (metabolism)
• Male
• NF-kappa B (metabolism)
• Neuroprotective Agents (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Subarachnoid Hemorrhage (complications, metabolism, pathology)
• Toll-Like Receptor 4 (metabolism)