Wogonin Improves Histological and Functional Outcomes, and Reduces Activation of TLR4/NF-κB Signaling after Experimental Traumatic Brain Injury

作者：Chien-Cheng Chen, Tai‐Ho Hung, Yen‐Ho Wang, Chii‐Wann Lin, Peiyi Wang, Chun-Yen Lee, Szu‐Fu Chen · 发表于：PLoS ONE · 年份：2012 · DOI：10.1371/journal.pone.0030294 · 被引用次数：82 · 研究领域：Traumatic Brain Injury and Neurovascular Disturbances、Neuroinflammation and Neurodegeneration Mechanisms、S100 Proteins and Annexins

BACKGROUND: Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to neuronal damage and behavioral impairment. This study was undertaken to investigate the effects of wogonin, a flavonoid with potent anti-inflammatory properties, on functional and histological outcomes, brain edema, and toll-like receptor 4 (TLR4)- and nuclear factor kappa B (NF-κB)-related signaling pathways in mice following TBI. METHODOLOGY/PRINCIPAL FINDINGS: Mice subjected to controlled cortical impact injury were injected with wogonin (20, 40, or 50 mg·kg(-1)) or vehicle 10 min after injury. Behavioral studies, histology analysis, and measurement of blood-brain barrier (BBB) permeability and brain water content were carried out to assess the effects of wogonin. Levels of TLR4/NF-κB-related inflammatory mediators were also examined. Treatment with 40 mg·kg(-1) wogonin significantly improved functional recovery and reduced contusion volumes up to post-injury day 28. Wogonin also significantly reduced neuronal death, BBB permeability, and brain edema beginning at day 1. These changes were associated with a marked reduction in leukocyte infiltration, microglial activation, TLR4 expression, NF-κB translocation to nucleus and its DNA binding activity, matrix metalloproteinase-9 activity, and expression of inflammatory mediators, including interleukin-1β, interleukin-6, macrophage inflammatory protein-2, and cyclooxygenase-2. CONCLUSIONS/SIGNIFICANCE: Our results show that post-i...