title: Pretreatment with tert-butylhydroquinone attenuates cerebral oxidative stress in mice after traumatic brain injury.
abstract: BACKGROUND
  Traumatic brain injury (TBI) is a worldwide health problem, identified as a major cause of death and disability. Increasing evidence has shown that oxidative stress plays an important role in TBI pathogenesis. The antioxidant transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), is a known mediator in protection against TBI-induced brain damage. The objective of this study was to test whether tert-butylhydroquinone (tBHQ), a novel Nrf2 activator, can protect against TBI-induced oxidative stress.
  
  
  METHODS
  Adult male imprinting control region mice were randomly divided into three groups: (1) sham + vehicle group; (2) TBI + vehicle group; and (3) TBI + tBHQ group. Closed-head brain injury was applied using the Feeney weight-drop method. We accessed the neurologic outcome of mice at 24 h after TBI, and subsequently measured protein levels of Nrf2 and the NOX2 subunit of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), the concentration of malondialdehyde, superoxide dismutase activity, and brain edema.
  
  
  RESULTS
  The NOX2 protein level was increased fivefold in the TBI + vehicle group, whereas pretreatment with tBHQ markedly attenuated the NOX2 protein expression relative to that in the TBI + vehicle group. TBI increased Nrf2 formation by 5% compared with the sham group, whereas treatment with tBHQ further upregulated the Nrf2 protein level by 12% compared with the sham group. The level of the oxidative damage marker malondialdehyde was reduced by 29% in the TBI + tBHQ group compared with the TBI + vehicle group, Moreover, pretreatment with tBHQ significantly increased the antioxidant enzyme superoxide dismutase activity. Administration of tBHQ also significantly decreased TBI-induced brain edema and neurologic deficits.
  
  
  CONCLUSIONS
  Pretreatment with tBHQ effectively attenuated markers of cerebral oxidative stress after TBI, thus supporting the testing of tBHQ as a potential neuroprotectant and adjunct therapy for TBI patients.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China; Department of Neurosurgery, People's Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China. Electronic address: njhdwang@hotmail.com.
authors.forename: Han-dong
authors.initials: HD
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001925:Brain Damage, Chronic / Q000209:etiology / Q000517:prevention & control; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control*; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D006873:Hydroquinones / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009460:Neurologic Examination; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D006873:Hydroquinones; D008562:Membrane Glycoproteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D008315:Malondialdehyde; C018855:2-tert-butylhydroquinone; D013482:Superoxide Dismutase; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
keywords: Nrf2; Oxidative stress; Traumatic brain injury; tBHQ