1. Metabolite differences between glutamate carboxypeptidase II gene knockout mice and their wild-type littermates after traumatic brain injury: a 7-tesla 1 H-MRS study.
- Author
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Wu W, Xu S, Wang J, Zhang K, Zhang M, Cao Y, Ren H, Zheng D, and Zhong C
- Subjects
- Animals, Aspartic Acid analogs & derivatives, Aspartic Acid metabolism, Brain diagnostic imaging, Brain Edema diagnostic imaging, Brain Edema etiology, Brain Edema metabolism, Brain Injuries, Traumatic diagnostic imaging, Disease Models, Animal, Glutamate Carboxypeptidase II genetics, Glutamic Acid metabolism, Magnetic Resonance Spectroscopy, Male, Mice, Knockout, Proton Magnetic Resonance Spectroscopy, Brain metabolism, Brain Injuries, Traumatic metabolism, Glutamate Carboxypeptidase II deficiency
- Abstract
Background: Traumatic brain injury (TBI) is a complex condition and remains a prominent public and medical health issue in individuals of all ages. A rapid increase in extracellular glutamate occurs after TBI, leading to glutamate-induced excitotoxicity, which causes neuronal damage and further functional impairments. Although inhibition of glutamate carboxypeptidase II (GCP II) is considered a potential approach for reducing glutamate-induced excitotoxicity after TBI, further detailed evidence regarding its efficacy is required. Therefore, in this study, we examined the differences in the metabolite status between wild-type (WT) and GCP II gene-knockout (KO) mice after TBI using proton magnetic resonance spectroscopy (1H-MRS) and T2-weighted magnetic resonance (MR) imaging with a 7-tesla imaging system, and brain water-content analysis., Results: Evaluation of glutamate and N-acetylaspartate concentrations revealed a decrease in both levels in the ipsilateral hippocampus at 24 h post-TBI; however, the reduction in glutamate and N-acetylaspartate levels was less marked in GCP II-KO mice than in WT mice (p < 0.05). T2 MR data and brain water-content analysis demonstrated that the extent of cortical edema and brain swelling was less in KO than in WT mice after TBI (p < 0.05)., Conclusion: Using two non-invasive methods, 1H-MRS and T2 MR imaging, as well as in vitro brain-water content measurements, we demonstrated that the mechanism underlying the neuroprotective effects of GCP II-KO against brain swelling in TBI involves changes in glutamate and N-acetylaspartate levels. This knowledge may contribute towards the development of therapeutic strategies for TBI.
- Published
- 2018
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