Metabolite differences between glutamate carboxypeptidase II gene knockout mice and their wild-type littermates after traumatic brain injury

a 7-tesla 1H-MRS study

Wenbo Wu, Siyi Xu, Jialin Wang, Kuiming Zhang, Mingkun Zhang, Yang Cao, Hongqing Ren, Deyou Zheng, Chunlong Zhong

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Number of pages1
JournalBMC Neuroscience
Volume19
Issue number1
DOIs
StatePublished - Nov 20 2018

Fingerprint

Glutamate Carboxypeptidase II
Gene Knockout Techniques
Knockout Mice
Glutamic Acid
Brain Edema
Water
Magnetic Resonance Imaging
Traumatic Brain Injury
Proton Magnetic Resonance Spectroscopy
Brain
Neuroprotective Agents
Neuroimaging
Hippocampus
Edema
Magnetic Resonance Spectroscopy
Public Health

Keywords

  • Brain edema
  • Glutamate
  • Glutamate carboxypeptidase II
  • Proton magnetic resonance spectroscopy (1H-MRS)
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience

Cite this

Metabolite differences between glutamate carboxypeptidase II gene knockout mice and their wild-type littermates after traumatic brain injury : a 7-tesla 1H-MRS study. / Wu, Wenbo; Xu, Siyi; Wang, Jialin; Zhang, Kuiming; Zhang, Mingkun; Cao, Yang; Ren, Hongqing; Zheng, Deyou; Zhong, Chunlong.

In: BMC Neuroscience, Vol. 19, No. 1, 20.11.2018.

Research output: Contribution to journalArticle

Wu, Wenbo ; Xu, Siyi ; Wang, Jialin ; Zhang, Kuiming ; Zhang, Mingkun ; Cao, Yang ; Ren, Hongqing ; Zheng, Deyou ; Zhong, Chunlong. / Metabolite differences between glutamate carboxypeptidase II gene knockout mice and their wild-type littermates after traumatic brain injury : a 7-tesla 1H-MRS study. In: BMC Neuroscience. 2018 ; Vol. 19, No. 1.
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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.",
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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

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

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 (1H-MRS)

KW - Traumatic brain injury

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U2 - 10.1186/s12868-018-0473-5

DO - 10.1186/s12868-018-0473-5

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JO - BMC Neuroscience

JF - BMC Neuroscience

SN - 1471-2202

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