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Unravelling the role of aging in post-stroke gut-brain axis signalling

Project description

The role of ageing in post-stroke intestinal immune responses

Stroke is preceded by an initial ischaemic phase, where peripheral and brain inflammatory responses affect remote organs and systems. Post-stroke, patients have a big susceptibility to bacterial infections, which are hypothesised to emerge as a consequence of changes in the permeability of the intestinal epithelial barrier. With ageing increasing the risk of stroke, the aim of the EU-funded immunogut project is to characterise the intestinal immune responses following brain ischaemia and delineate the contribution of ageing to these responses. Results will shed light on the role of intestinal immune responses in stroke outcome and determine whether modulation can serve as a potential therapeutic approach.

Objective

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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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2019

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Coordinator

THE HEBREW UNIVERSITY OF JERUSALEM
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 269 998,08
Address
EDMOND J SAFRA CAMPUS GIVAT RAM
91904 JERUSALEM
Israel

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Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 269 998,08

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