In situ metabolite and lipid analysis of GluN2D−/− and wild-type mice after ischemic stroke using MALDI MSI

Andrews, William T.; Donahue, Deborah L.; Holmes, Adam; Balsara, Rashna D.; Hummon, Amanda B.

doi:10.1007/s00216-020-02477-z

Cited by 14 publications

(8 citation statements)

References 59 publications

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“…It is noteworthy that the effects may be conflicting in different cell types and models [ 139 ]. For example, in vitro or MCAO models, neurological recovery was enhanced in GluN2C and GluN2D knockout mice, and GluN2D antagonists blocked cortical neuronal NMDAR toxicity [ 140 , 141 , 142 ]. Triggering the GluN2C/2D subunit in oligodendrocytes can also lead to myelin damage and white matter dysfunction [ 143 ].…”

Section: Postsynaptic Effect Of Glutamate As the Main Mechanism Of Ne...mentioning

confidence: 99%

Excitatory Synaptic Transmission in Ischemic Stroke: A New Outlet for Classical Neuroprotective Strategies

Fan

Xie

Xing

et al. 2022

IJMS

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Stroke is one of the leading causes of death and disability in the world, of which ischemia accounts for the majority. There is growing evidence of changes in synaptic connections and neural network functions in the brain of stroke patients. Currently, the studies on these neurobiological alterations mainly focus on the principle of glutamate excitotoxicity, and the corresponding neuroprotective strategies are limited to blocking the overactivation of ionic glutamate receptors. Nevertheless, it is disappointing that these treatments often fail because of the unspecificity and serious side effects of the tested drugs in clinical trials. Thus, in the prevention and treatment of stroke, finding and developing new targets of neuroprotective intervention is still the focus and goal of research in this field. In this review, we focus on the whole processes of glutamatergic synaptic transmission and highlight the pathological changes underlying each link to help develop potential therapeutic strategies for ischemic brain damage. These strategies include: (1) controlling the synaptic or extra-synaptic release of glutamate, (2) selectively blocking the action of the glutamate receptor NMDAR subunit, (3) increasing glutamate metabolism, and reuptake in the brain and blood, and (4) regulating the glutamate system by GABA receptors and the microbiota–gut–brain axis. Based on these latest findings, it is expected to promote a substantial understanding of the complex glutamate signal transduction mechanism, thereby providing excellent neuroprotection research direction for human ischemic stroke (IS).

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Section: Postsynaptic Effect Of Glutamate As the Main Mechanism Of Ne...mentioning

confidence: 99%

Excitatory Synaptic Transmission in Ischemic Stroke: A New Outlet for Classical Neuroprotective Strategies

Fan

Xie

Xing

et al. 2022

IJMS

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“…These trends suggest that GluN2D −/− mice show a higher rate of neurological recovery and neuroprotection against ischemic stroke compared to wild-type mice. The neuroprotective cause may be the result of increased PGP in knockout mice, which contributes to increased cardiolin synthesis and reduced sensitivity to apoptotic signals (Andrews, Donahue et al, 2020). A combination of analytical methods, including mass spectrometry, provides detailed information about the content and distribution of lipids and their oxidation products, and thus constitutes an emerging field of oxidized lipidomics.…”

Section: Lipidsmentioning

confidence: 99%

Mass Spectrometry Imaging as a New Method: To Reveal the Pathogenesis and the Mechanism of Traditional Medicine in Cerebral Ischemia

2022

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Mass spectrometry imaging (MSI) can describe the spatial distribution of molecules in various complex biological samples, such as metabolites, lipids, peptides and proteins in a comprehensive way, and can provide highly relevant supplementary information when combined with other molecular imaging techniques and chromatography techniques, so it has been used more and more widely in biomedical research. The application of mass spectrometry imaging in neuroscience is developing. It is very advantageous and necessary to use MSI to study various pathophysiological processes involved in brain injury and functional recovery during cerebral ischemia. Therefore, this paper introduces the techniques of mass spectrometry, including the principle of mass spectrometry, the acquisition and preparation of imaging samples, the commonly used ionization techniques, and the optimization of the current applied methodology. Furthermore, the research on the mechanism of cerebral ischemia by mass spectrometry was reviewed, such as phosphatidylcholine involved, dopamine, spatial distribution and level changes of physiological substances such as ATP in the Krebs cycle; The characteristics of mass spectrometry imaging as one of the methods of metabolomics in screening biomarkers related to cerebral ischemia were analyzed the advantages of MSI in revealing drug distribution and the mechanism of traditional drugs were summarized, and the existing problems of MSI were also analyzed and relevant suggestions were put forward.

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“…For example, fresh frozen bone samples have been imaged resulting in discovery of unique signatures associated with bone marrow and soft tissues 1 , and phospholipids have been mapped in a Drosophila model of amyotrophic lateral sclerosis brain tissue 2 . Other examples include lipid mapping in cancer models 3 , ischemic stroke 4 , and of the human retina 5 .…”

Section: Introductionmentioning

confidence: 99%

DBDA matrix increases ion abundance of fatty acids and sulfatides in MALDI-TOF and mass spectrometry imaging studies

Khamidova

Pergande

Pathmasiri

et al. 2023

Preprint

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MALDI-TOF MS is a powerful tool to analyze biomolecules owing to its soft ionization nature and generally results in simple spectra of singly charged ions. Moreover, implementation of the technology in imaging mode provides a means to spatially map analytes in situ. Recently, a new matrix, DBDA (N1,N4-dibenzylidenebenzene-1,4-diamine) was reported to facilitate the ionization of free fatty acids in the negative ion mode. Building on this finding, we sought to implement DBDA for MALDI mass spectrometry imaging studies in brain tissue and successfully map oleic acid, palmitic acid, stearic acid, docosahexaenoic acid and arachidonic acid using mouse brain sections. Moreover, we hypothesized that DBDA would provide superior ionization for sulfatides, a class of sulfolipids, with multiple biological functions. Herein we also demonstrate that DBDA is ideal for MALDI mass spectrometry imaging of fatty acids and sulfatides in brain tissue sections. Additionally, we show enhanced ionization of sulfatides using DBDA compared to three different traditionally used MALDI matrices. Together these results provide new opportunities for studies to measure sulfatides by MALDI-TOF MS including in imaging modes.

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In situ metabolite and lipid analysis of GluN2D−/− and wild-type mice after ischemic stroke using MALDI MSI

Cited by 14 publications

References 59 publications

Excitatory Synaptic Transmission in Ischemic Stroke: A New Outlet for Classical Neuroprotective Strategies

Excitatory Synaptic Transmission in Ischemic Stroke: A New Outlet for Classical Neuroprotective Strategies

Mass Spectrometry Imaging as a New Method: To Reveal the Pathogenesis and the Mechanism of Traditional Medicine in Cerebral Ischemia

DBDA matrix increases ion abundance of fatty acids and sulfatides in MALDI-TOF and mass spectrometry imaging studies

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