In Vitro Oxygen Glucose Deprivation Model of Ischemic Stroke: A Proteomics-Driven Systems Biological Perspective

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.