Abstract
Oxygen glucose deprivation (OGD) of brain cells is the commonest in vitro model of ischemic stroke that is used extensively for basic and preclinical stroke research. Protein mass spectrometry is one of the most promising and rapidly evolving technologies in biomedical research. A systems-level understanding of cell-type-specific responses to oxygen and glucose deprivation without systemic influence is a prerequisite to delineate the response of the neurovascular unit following ischemic stroke. In this systematic review, we summarize the proteomics studies done on different OGD models. These studies have followed an expression or interaction proteomics approach. They have been primarily used to understand the cellular pathophysiology of ischemia-reperfusion injury or to assess the efficacy of interventions as potential treatment options. We compile the limitations of OGD model and downstream proteomics experiment. We further show that despite having limitations, several proteins shortlisted as altered in in vitro OGD-proteomics studies showed comparable regulation in ischemic stroke patients. This showcases the translational potential of this approach for therapeutic target and biomarker discovery. We next discuss the approaches that can be adopted for cell-type-specific validation of OGD-proteomics results in the future. Finally, we briefly present the research questions that can be addressed by OGD-proteomics studies using emerging techniques of protein mass spectrometry. We have also created a web resource compiling information from OGD-proteomics studies to facilitate data sharing for community usage. This review intends to encourage preclinical stroke community to adopt a hypothesis-free proteomics approach to understand cell-type-specific responses following ischemic stroke.
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Data Availability
Supplementary materials are available. A web resource containing supplementary tables and vector graphic version of a modified Fig. 3 are available at https://yenepoya.res.in/database/LTN_Datta_Lab/OGD-Prot_Systematic-Review/
Abbreviations
- OGD:
-
Oxygen glucose deprivation
- CSF:
-
Cerebrospinal fluid
- MALDI:
-
Matrix-assisted laser desorption ionization
- 2D-GE:
-
Two-dimensional gel electrophoresis
- ICAT:
-
Isotope-coded affinity tag
- iTRAQ:
-
Isobaric tags for relative and absolute quantitation
- TMT:
-
Tandem mass tags
- MPT:
-
Mitochondrial permeability transition
- ROS:
-
Reactive oxygen species
- EV:
-
Extracellular vesicles
- PMI:
-
Post mortem interval
- LCM:
-
Laser-capture microdissection
- PRM:
-
Parallel reaction monitoring
- SRM:
-
Single reaction monitoring
- MRM:
-
Multiple reaction monitoring
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Acknowledgements
The authors thank Sudheer Shenoy, Bipasha Bose, and Rekha PD for helpful discussions and Klaus Heese for critical reading of the manuscript.
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The study is funded in part by departmental funding at Yenepoya Research Center and an institutional seed grant (YU/Seed Grant/092–2020 to A.D.) at Yenepoya (Deemed to be University). M.B. is funded by a senior research fellowship from Yenepoya (Deemed to be University).
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Conceptualization: A.D. Literature search and analysis: M.B., N.K., and A.D. Preparation of tables, figures, web resource: M.B., N.K. and A.D. Writing and editing: A.D. All authors approved the final version of the manuscript.
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Common abbreviations such as DMEM, MEM, HBSS, BSS, FBS, MAPK, MTT, LDH, RT-PCR, ELISA, siRNA, miRNA, and CRISPR-Cas9 are not included. In vitro OGD-proteomics studies have been done on cells of human and non-human origin. To designate proteins irrespective of the origin, non-italicized gene symbols in uppercase (corresponds to human origin) are used.
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Babu, M., Singh, N. & Datta, A. In Vitro Oxygen Glucose Deprivation Model of Ischemic Stroke: A Proteomics-Driven Systems Biological Perspective. Mol Neurobiol 59, 2363–2377 (2022). https://doi.org/10.1007/s12035-022-02745-2
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DOI: https://doi.org/10.1007/s12035-022-02745-2