title: Wogonin improves histological and functional outcomes, and reduces activation of TLR4/NF-κB signaling after experimental traumatic brain injury.
abstract: 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.
authors.affiliation: Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Chien-Cheng
authors.initials: CC
authors.lastname: Chen
authors.forename: Tai-Ho
authors.initials: TH
authors.lastname: Hung
authors.forename: Yen-Ho
authors.initials: YH
authors.lastname: Wang
authors.forename: Chii-Wann
authors.initials: CW
authors.lastname: Lin
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Wang
authors.forename: Chun-Yen
authors.initials: CY
authors.lastname: Lee
authors.forename: Szu-Fu
authors.initials: SF
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D015153:Blotting, Western; D001929:Brain Edema / Q000517:prevention & control; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D054426:Chemokine CXCL2 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D044950:Flavanones / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D008517:Phytotherapy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D054426:Chemokine CXCL2; D004365:Drugs, Chinese Herbal; D044950:Flavanones; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C085514:wogonin