TY - JOUR
T1 - Metabolite differences between glutamate carboxypeptidase II gene knockout mice and their wild-type littermates after traumatic brain injury
T2 - A 7-tesla 1H-MRS study 11 Medical and Health Sciences 1109 Neurosciences
AU - Wu, Wenbo
AU - Xu, Siyi
AU - Wang, Jialin
AU - Zhang, Kuiming
AU - Zhang, Mingkun
AU - Cao, Yang
AU - Ren, Hongqing
AU - Zheng, Deyou
AU - Zhong, Chunlong
N1 - Funding Information:
We received funds from the National Natural Science Foundation of China (Nos. 81771332, 81571184, 81070990), Shanghai Key Medical Discipline for Critical Care Medicine (No. 2017ZZ02017), and Key Discipline Construction Project of Pudong Health Bureau of Shanghai (Nos. PWZxk2017-23, PWYgf2018-05) in the process of study design, experiment implementation and data collection.
Funding Information:
This study was supported in part by Center of Biomedical Imaging, Fudan University, Shanghai 200032, China. And Prof. Bingwen Hu from East China Normal University contributed to the data analysis.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/11/20
Y1 - 2018/11/20
N2 - 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.
AB - 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.
KW - Brain edema
KW - Glutamate
KW - Glutamate carboxypeptidase II
KW - Proton magnetic resonance spectroscopy (H-MRS)
KW - Traumatic brain injury
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U2 - 10.1186/s12868-018-0473-5
DO - 10.1186/s12868-018-0473-5
M3 - Article
C2 - 30458729
AN - SCOPUS:85056802283
VL - 19
JO - BMC Neuroscience
JF - BMC Neuroscience
SN - 1471-2202
IS - 1
M1 - 75
ER -