title: Glutamate carboxypeptidase II gene knockout attenuates oxidative stress and cortical apoptosis after traumatic brain injury.
abstract: BACKGROUND
  Glutamate carboxypeptidase II (GCPII) inactivates the peptide co-transmitter N-acetylaspartylglutamate following synaptic release. Inhibition of GCPII elevates extracellular levels of the peptide, inhibits glutamate release and is neuroprotective in an animal model of traumatic brain injury. GCPII gene knockout mice were used to examine the cellular mechanisms underlying the neuroprotective efficacy of this transmitter system.
  
  
  RESULTS
  Following controlled cortical impact injury, GCPII knockout (KO) mice exhibited reduced TUNEL-positive nuclei in the contusion margin of the cerebral cortex relative to wild type mice. Impact injury reduced glutathione levels and superoxide dismutase and glutathione peroxidase activities and increased malondialdehyde. Each of these effects was moderated in KO mice relative to wild type. Similarly, the injury-induced increases in cleaved caspase-3, cytosolic cytochrome c levels and Bcl-2/Bax ratio observed in wild type mice were attenuated in the knockout mice.
  
  
  CONCLUSIONS
  These data support the hypothesis that the neuroprotective efficacy of GCPII KO in traumatic brain injury is mediated via a reduction in oxidative stress.
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
authors.forename: Siyi
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
authors.forename: Jingang
authors.initials: J
authors.lastname: Bao
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Psychiatry, Yale University, School of Medicine, West Haven, CT, 06516, USA.
authors.forename: Xingguang
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
authors.forename: Qizhong
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
authors.forename: Jiyao
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Biology, Georgetown University, Washington, DC, 20075, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Neale
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. drchunlongzhong@126.com.
authors.forename: Chunlong
authors.initials: C
authors.lastname: Zhong
mesh_terms: D000818:Animals; D017209:Apoptosis; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology*; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology*; D043425:Glutamate Carboxypeptidase II / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D043425:Glutamate Carboxypeptidase II; D053148:Caspase 3
keywords: Apoptosis; Gene knockout; Glutamate carboxypeptidase II; NAAG; Oxidative stress; Traumatic brain injury