Wogonin improves histological and functional outcomes, and reduces activation of TLR4/NF-κB signaling after experimental traumatic brain injury

• Published in: PloS one Vol. 7; no. 1; p. e30294
• Main Authors: Chen, Chien-Cheng, Hung, Tai-Ho, Wang, Yen-Ho, Lin, Chii-Wann, Wang, Pei-Yi, Lee, Chun-Yen, Chen, Szu-Fu
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2012; Public Library of Science (PLoS)
• Subjects: Animals; Anti-inflammatory agents; Apoptosis; Apoptosis - drug effects; Biology; Biomedical engineering; Blood-brain barrier; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - physiopathology; Blotting, Western; Brain damage; Brain Edema - prevention & control; Brain Injuries - drug therapy; Brain Injuries - metabolism; Brain Injuries - physiopathology; Cell activation; Chemokine CXCL2 - genetics; Chemokine CXCL2 - metabolism; Chemokines; Cortex; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Cytokines; Deoxyribonucleic acid; DNA; Drugs, Chinese Herbal - pharmacology; Edema; Enzyme-Linked Immunosorbent Assay; Flavanones - pharmacology; Flavonoids; Gene expression; Gene Expression - drug effects; Head injuries; Histology; Hospitals; Immune system; In Situ Nick-End Labeling; Infiltration; Inflammation; Inflammatory response; Injury analysis; Injury prevention; Interleukin; Interleukin 6; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Interleukin-6 - genetics; Interleukin-6 - metabolism; Ischemia; Kinases; Leukocytes; Localization; Macrophage inflammatory protein; Macrophages; Male; Matrix metalloproteinase; Medicine; Membrane permeability; Metabolism; Metalloproteinase; Mice; Mice, Inbred C57BL; Moisture content; Neuroprotection; NF-kappa B - metabolism; NF-κB protein; Permeability; Permeability - drug effects; Phytotherapy; Proteins; Recovery of function; Rehabilitation; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Scutellaria baicalensis; Signal transduction; Signal Transduction - drug effects; Signaling; Studies; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Translocation; Traumatic brain injury; Water content; White blood cells; China; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0030294

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. 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. Our results show that post-injury wogonin treatment improved long-term functional and histological outcomes, reduced brain edema, and attenuated the TLR4/NF-κB-mediated inflammatory response in mouse TBI. The neuroprotective effects of wogonin may be related to modulation of the TLR4/NF-κB signaling pathway.