Summary
Stroke is a multiphasic process, with an initial ischemic phase followed by secondary progression of injury from inflammatory responses which affects and being affected by remote organs and systems outside of the central nervous system. The gastrointestinal tract constantly communicates with the brain in a complex network of interactions generally termed the ‘gut-brain axis’. Following brain ischemia, the intestinal epithelial barrier becomes permeable, exposing gut immune cells to extrinsic molecules and contributing to late post-stroke bacterial infections. It is yet completely unknown whether the consequent intestinal immune response contributes to stroke outcomes and if its modulation can serve as a potential therapeutic approach. Aging significantly increases the vulnerability to both stroke and GI disorders. I hypothesize, that changes in gut permeability after stroke contribute to the peripheral and brain innate immune responses. This is likely to be aggravated in aging, where stroke is associated with enhanced bacterial translocation and susceptibility to develop post-stroke infections. In order to test this hypothesis, I need to first characterize the time course and nature of the intestinal immune response after stroke, using flow cytometry to identify dynamics of immune cell activation. Building on my previous experience in neuroimmuology and gut-brain axis research, including high throughput multi-omics approaches to address host-microbial interactions in the context of neurological diseases, transcriptomics and metabolomics during both my PhD (Tell-Aviv Uni) and first postdoc (Weizmann Institute of Science), I will utilize a combination of flow-cytometry, multiplexed single-cell quantification of cellular spatial interactions (CODEX), in-vivo models and quantitative network analysis to characterize the intestinal immune response in stroke in order to delineate the contribution of aging to post-stroke intestinal immune responses.
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| Web resources: | https://cordis.europa.eu/project/id/888494 |
| Start date: | 01-09-2020 |
| End date: | 31-08-2023 |
| Total budget - Public funding: | 269 998,08 Euro - 269 998,00 Euro |
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Original description
Stroke is a multiphasic process, with an initial ischemic phase followed by secondary progression of injury from inflammatory responses which affects and being affected by remote organs and systems outside of the central nervous system. The gastrointestinal tract constantly communicates with the brain in a complex network of interactions generally termed the ‘gut-brain axis’. Following brain ischemia, the intestinal epithelial barrier becomes permeable, exposing gut immune cells to extrinsic molecules and contributing to late post-stroke bacterial infections. It is yet completely unknown whether the consequent intestinal immune response contributes to stroke outcomes and if its modulation can serve as a potential therapeutic approach. Aging significantly increases the vulnerability to both stroke and GI disorders. I hypothesize, that changes in gut permeability after stroke contribute to the peripheral and brain innate immune responses. This is likely to be aggravated in aging, where stroke is associated with enhanced bacterial translocation and susceptibility to develop post-stroke infections. In order to test this hypothesis, I need to first characterize the time course and nature of the intestinal immune response after stroke, using flow cytometry to identify dynamics of immune cell activation. Building on my previous experience in neuroimmuology and gut-brain axis research, including high throughput multi-omics approaches to address host-microbial interactions in the context of neurological diseases, transcriptomics and metabolomics during both my PhD (Tell-Aviv Uni) and first postdoc (Weizmann Institute of Science), I will utilize a combination of flow-cytometry, multiplexed single-cell quantification of cellular spatial interactions (CODEX), in-vivo models and quantitative network analysis to characterize the intestinal immune response in stroke in order to delineate the contribution of aging to post-stroke intestinal immune responses.Status
CLOSEDCall topic
MSCA-IF-2019Update Date
28-04-2024
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