Altered Neurochemical Profile after Traumatic Brain Injury: 1H-MRS Biomarkers of Pathological Mechanisms

Specific neurochemicals measured with proton magnetic resonance spectroscopy (1H-MRS) may serve as biomarkers of pathological mechanism in the brain. We used high field in vivo1H-MRS to measure a detailed neurochemical profile after experimental traumatic brain injury (TBI) in rats. We characterized neurochemical changes in the contused cortex and the normal-appearing perilesional hippocampus over a time course from 1 hour to 2 weeks after injury. We found significant changes in 19 out of 20 neurochemicals in the cortex, and 9 out of 20 neurochemicals in the hippocampus. These changes provide evidence of altered cellular metabolic status after TBI, with specific compounds proposed to reflect edema, excitotoxicity, neuronal and glial integrity, mitochondrial status and bioenergetics, oxidative stress, inflammation, and cell membrane disruption. Our results support the utility of 1H-MRS for monitoring cellular mechanisms of TBI pathology in animal models, and the potential of this approach for preclinical evaluation of novel therapies.

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Traumatic Brain Injury and Subarachnoid Hemorrhage: In Vivo Occult Pathology Demonstrated by Magnetic Resonance Spectroscopy may not be "Ischaemic". A Primary Study and Review of the Literature

Acta Neurochirurgica ◽

10.1007/s00701-002-0966-x ◽

2002 ◽

Vol 144 (9) ◽

pp. 853-862 ◽

Cited By ~ 38

Author(s):

C. S. A. Macmillan ◽

J. M. Wild ◽

J. M. Wardlaw ◽

P. J. D. Andrews ◽

I. Marshall ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Subarachnoid Hemorrhage ◽

Brain Injury ◽

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Primary Study ◽

Resonance Spectroscopy ◽

Review Of The Literature

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Role of Magnetic Resonance Spectroscopy for Prognosis of Patients with Traumatic Brain Injury

Indian Journal of Neurotrauma ◽

10.1055/s-0037-1612649 ◽

2017 ◽

Vol 14 (02/03) ◽

pp. 075-082

Author(s):

Raghuvendra Kumar ◽

Subhasis Ghosh ◽

Tapan Dhibar ◽

Abhishek Kumar

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Control Group ◽

Resonance Spectroscopy ◽

1H Mrs ◽

Computed Tomographic ◽

Severity Of Injury ◽

Degree Of Severity

Abstract Background Traumatic brain injury (TBI) is one of the leading causes of death worldwide. Long-term clinical outcome following TBI can be difficult to predict. Evaluation of the degree of severity of injury and prediction of outcome are important for the management of these patients. Objective To evaluate whether degree of severity of injury and outcome in moderate to severe TBI is possible by proton magnetic resonance spectroscopy (1H-MRS). Materials and Methods Patients with moderate (Glasgow coma scale [GCS] 9–13) and severe head injury (GCS: 5–8), within 1 week of trauma with their normal computed tomographic (CT) scan findings, their magnetic resonance imaging (MRI) finding, and neurologic status were investigated with single-voxel proton MRS (1H-MRS). The study included 51 patients and 24 controls. Result The MRS study revealed lower ratio of N-acetylaspartate (NAA)/choline (Cho) and NAA/creatine (Cr) and higher ratio of Cho/Cr and lactate level compared with the control group. The ratio of NAA/Cr, NAA/Cho, and Cho/Cr were statistically significant with initial GCS (p = < 0.00001, r = 0.7595; p = < 0.00001, r = 0.7506; and p < 0.00001, r = −0.5923, respectively), and these ratios were also statistically significant with Glasgow outcome scale (GOS) (p < 0.00001, r = 0.8498, p < 0.00001, r =0.9323, p < 0.00001, r = −0.9082, respectively). The ratio of NAA/Cr, NAA/Cho, and Cho/Cr were also statistically significant with severity of injury (p < 0.0001). Conclusion MRS can quantify damage after TBI and may be a method of assessing severity and outcome in TBI.

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The Clinical Utility of Magnetic Resonance Spectroscopy in Traumatic Brain Injury: Recommendations from the ENIGMA MRS Working Group

10.31234/osf.io/gesvh ◽

2019 ◽

Cited By ~ 4

Author(s):

Brenda L. Bartnik-Olson ◽

Jeffry Alger ◽

Talin Babikian ◽

Ashley D Harris ◽

Barbara Holshouser ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Cerebral Metabolism ◽

Quantitative Measure ◽

Resonance Spectroscopy ◽

Imaging Protocol ◽

Acquisition Scheme

Proton magnetic resonance spectroscopy provides a non-invasive and quantitative measure of brain metabolites. Traumatic brain injury impacts cerebral metabolism and a number of research groups have successfully used this technique as a biomarker of injury and/or outcome in both pediatric and adult TBI populations. However, this technique is underutilized, with studies being performed primarily at centers with access to MR research support. In this paper we present a technical introduction to the acquisition and analysis of in vivo magnetic resonance spectroscopy and review magnetic resonance spectroscopy findings in different injury populations. In addition, we propose a basic data acquisition scheme that can be added to any imaging protocol, regardless of clinical magnetic resonance platform. We outline a number of considerations for study design as a way of encouraging the use of magnetic resonance spectroscopy in the study of traumatic brain injury, as well as recommendations to improve data harmonization across groups already using this technique.

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Glutamate and GABA concentrations following mild traumatic brain injury: a pilot study

Journal of Neurophysiology ◽

10.1152/jn.00896.2017 ◽

2018 ◽

Vol 120 (3) ◽

pp. 1318-1322 ◽

Cited By ~ 6

Author(s):

Alia L. Yasen ◽

Jolinda Smith ◽

Anita D. Christie

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mild Traumatic Brain Injury ◽

Primary Motor Cortex ◽

Brain Regions ◽

Resonance Spectroscopy ◽

Multiple Time ◽

Time Points ◽

The Brain

Animal models of mild traumatic brain injury (mTBI) suggest that metabolic changes in the brain occur immediately after a mechanical injury to the head. Proton magnetic resonance spectroscopy (1H-MRS) can be used to determine relative concentrations of metabolites in vivo in the human brain. The purpose of this study was to determine concentrations of glutamate and GABA in the brain acutely after mTBI and throughout 2 mo of recovery. Concentrations of glutamate and GABA were obtained using 1H-MRS in nine individuals who had suffered an mTBI and nine control individuals in two brain regions of interest: the primary motor cortex (M1), and the dorsolateral prefrontal cortex (DLPFC), and at three different time points postinjury: 72 h, 2 wk, and 2 mo postinjury. There were no differences between groups in concentrations of glutamate or GABA, or the ratio of glutamate to GABA, in M1. In the DLPFC, glutamate concentration was lower in the mTBI group compared with controls at 72 h postinjury (d = 1.02), and GABA concentration was lower in the mTBI group at 72 h and 2 wk postinjury (d = 0.81 and d = 1.21, respectively). The ratio of glutamate to GABA in the DLPFC was higher in the mTBI group at 2 wk postinjury (d = 1.63). These results suggest that changes in glutamate and GABA concentrations in the brain may be region-specific and may depend on the amount of time that has elapsed postinjury. NEW & NOTEWORTHY To our knowledge, this is the first study to examine neurotransmitter concentrations in vivo at multiple time points throughout recovery from mild traumatic brain injury in humans.

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In vivo MR spectroscopy reflects synapse density in a Huntington′s disease mouse model

10.1101/2021.10.26.465951 ◽

2021 ◽

Author(s):

Nicole Zarate ◽

Katherine Gundry ◽

Dahyun Yu ◽

Jordan Casby ◽

Lynn E Eberly ◽

...

Keyword(s):

Mouse Model ◽

Ex Vivo ◽

Imaging Techniques ◽

Excitatory Synapse ◽

Resonance Spectroscopy ◽

1H Mrs ◽

Synaptic Circuits ◽

Synapse Density ◽

Neurochemical Changes

Background: Striatal medium spiny neurons are highly susceptible in Huntington′s disease (HD), resulting in early synaptic perturbations that lead to neuronal dysfunction and death. Non-invasive imaging techniques, such as proton magnetic resonance spectroscopy (1H-MRS), have been used in HD mouse models and patients with HD to monitor neurochemical changes associated with neuronal health. However, the molecular connection between brain neurochemical alterations and synaptic dysregulation is unknown, limiting our ability to monitor potential treatments that may affect synapse function. Objective: Assess the intersection of synapse density and 1H-MRS during disease progression in an HD mouse model. Methods: We conducted in vivo longitudinal 1H-MRS in the striatum followed by ex-vivo analyses of excitatory synapse density of two synaptic circuits disrupted in HD: thalamo-striatal (T-S) and cortico-striatal (C-S) pathways. We used the heterozygous knock-in zQ175 HD mouse model as well as zQ175 mice lacking one allele of CK2α′(zQ175(Tg/0):CK2α′(+/-)), a kinase previously shown to regulate synapse function in HD. Results: Longitudinal analyses of excitatory synapse density showed early and sustained reduction in T-S synapses in zQ175 mice, preceding C-S synapse depletion, which was rescued in zQ175:CK2α′(+/-). Linear regression analyses showed C-S synapse number correlated with 1H-MRS-measured levels of GABA while T-S synapse number positively correlated with alterations in the levels of alanine, phosphoethanolamine, lactate, and taurine relative to total creatine. Conclusion: We propose these neurochemicals could be used as surrogate biomarkers to monitor circuit-specific synaptic dysfunction using 1H-MRS in the zQ175 mouse model and perhaps in HD pre-clinical studies.

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