Glutamate carboxypeptidase II gene knockout attenuates oxidative stress and cortical apoptosis after traumatic brain injury

BMC Neuroscience

Research Article

Joseph H. Neale¹  Jiyao Jiang²  Yang Cao²  Yang Gao²  Yingying Lin²  Yong Wang²  Chunlong Zhong²  Jingang Bao²  Qizhong Luo²  Siyi Xu²  Xingguang Luo³ 

[1] Department of Biology, Georgetown University, 20075, Washington, DC, USA;Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, 200127, Shanghai, China;Department of Psychiatry, Yale University, School of Medicine, 06516, West Haven, CT, USA;

关键词: NAAG;    Glutamate carboxypeptidase II;    Gene knockout;    Traumatic brain injury;    Oxidative stress;    Apoptosis;   

DOI  :  10.1186/s12868-016-0251-1

 received in 2016-02-02, accepted in 2016-04-13,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundGlutamate 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.ResultsFollowing 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.ConclusionsThese data support the hypothesis that the neuroprotective efficacy of GCPII KO in traumatic brain injury is mediated via a reduction in oxidative stress.

【 授权许可】

CC BY   
© Cao et al. 2016