Back to Search
Start Over
Glutamate carboxypeptidase II gene knockout attenuates oxidative stress and cortical apoptosis after traumatic brain injury.
- Source :
-
BMC neuroscience [BMC Neurosci] 2016 Apr 18; Vol. 17, pp. 15. Date of Electronic Publication: 2016 Apr 18. - Publication Year :
- 2016
-
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.<br />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.<br />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.
- Subjects :
- Animals
Caspase 3 metabolism
Glutamate Carboxypeptidase II genetics
Male
Mice
Mice, Knockout
Mitochondria metabolism
Proto-Oncogene Proteins c-bcl-2 metabolism
bcl-2-Associated X Protein metabolism
Apoptosis
Brain Injuries metabolism
Brain Injuries physiopathology
Cerebral Cortex metabolism
Cerebral Cortex physiopathology
Glutamate Carboxypeptidase II physiology
Oxidative Stress
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2202
- Volume :
- 17
- Database :
- MEDLINE
- Journal :
- BMC neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 27091009
- Full Text :
- https://doi.org/10.1186/s12868-016-0251-1