Neuroimaging is the new "spatial omic": multi-omic approaches to neuro-inflammation and immuno-thrombosis in acute ischemic stroke.
Benjamin MaïerAmy S TsaiJakob F EinhausJean-Philippe DesillesBenoît Ho-Tin-NoéBenjamin GoryMarina SirotaRichard LeighRobin LemmensGregory AlbersJean-Marc OlivotMichael MazighiBrice GaudillièrePublished in: Seminars in immunopathology (2023)
Ischemic stroke (IS) is the leading cause of acquired disability and the second leading cause of dementia and mortality. Current treatments for IS are primarily focused on revascularization of the occluded artery. However, only 10% of patients are eligible for revascularization and 50% of revascularized patients remain disabled at 3 months. Accumulating evidence highlight the prognostic significance of the neuro- and thrombo-inflammatory response after IS. However, several randomized trials of promising immunosuppressive or immunomodulatory drugs failed to show positive results. Insufficient understanding of inter-patient variability in the cellular, functional, and spatial organization of the inflammatory response to IS likely contributed to the failure to translate preclinical findings into successful clinical trials. The inflammatory response to IS involves complex interactions between neuronal, glial, and immune cell subsets across multiple immunological compartments, including the blood-brain barrier, the meningeal lymphatic vessels, the choroid plexus, and the skull bone marrow. Here, we review the neuro- and thrombo-inflammatory responses to IS. We discuss how clinical imaging and single-cell omic technologies have refined our understanding of the spatial organization of pathobiological processes driving clinical outcomes in patients with an IS. We also introduce recent developments in machine learning statistical methods for the integration of multi-omic data (biological and radiological) to identify patient-specific inflammatory states predictive of IS clinical outcomes.
Keyphrases
- end stage renal disease
- inflammatory response
- machine learning
- oxidative stress
- clinical trial
- ejection fraction
- bone marrow
- chronic kidney disease
- single cell
- newly diagnosed
- prognostic factors
- percutaneous coronary intervention
- high resolution
- stem cells
- lymph node
- cardiovascular disease
- pulmonary embolism
- mesenchymal stem cells
- big data
- mass spectrometry
- brain injury
- lipopolysaccharide induced
- coronary artery disease
- toll like receptor
- study protocol
- fluorescence imaging
- data analysis