Project description
Tissue damage and neuroinflammation in strokes
Strokes are closely associated with the death of brain tissue, often resulting in mortality or long-term disability for survivors. This damage is worsened by tissue necrosis and the release of chromatin, extracellular nucleosomes, DNA, histones (ExNDH), which intensify the initial injury and trigger inflammation. Despite their significance, the mechanisms underlying these processes remain poorly understood. Supported by the Marie Skłodowska-Curie Actions programme, the ExNDH-Stroke project will investigate the origins, mechanisms, and consequences of ExNDH in the extracellular space. It will explore when, where, and how ExNDH emerge, whether they are sequestered by extracellular microvesicles or matrices, their fate in the vasculature and brain parenchyma, and how various stroke treatments affect these pathways. The project aims to improve both stroke research and patient care.
Objective
Stroke is associated with the death of brain tissue and is a significant cause of mortality and disability among survivors. Tissue necrosis, in addition to the active release of chromatin by activated neutrophils, a process known as NETosis, results in the release of extracellular nucleosomes, DNA, and histones (ExNDH). Such processes serve to exacerbate the initial tissue injury and promote a pro-inflammatory state, thereby amplifying the original injury. The evidence supporting this hypothesis is that the inhibition of histones, the degradation of DNA, the depletion of infiltrated neutrophils and the blocking of NETosis all result in an improvement in the outcome of stroke. While the cellular effects of ExNDH are well documented, there remain significant unanswered questions. It is yet unclear where, when, and how they arise in the extracellular space. Are they sequestered by the extracellular matrix or microvesicles? What is the fate of these substances within the vasculature and the brain parenchyma? What impact do different stroke treatment modalities have on these pathways? The objective of this project is to address these questions in vivo in a systematic manner, thereby filling a significant gap in our understanding of stroke pathophysiology. To approach these matters, I will locally express fluorescent histone protein in the brain of mice using lentiviruses, induce stroke, and track the movement of fluorescent histones using immunofluorescence analysis and two-photon microscopy. By elucidating the distinctive molecular mechanisms that disrupt the detrimental feedback loop of neuronal damage following a stroke, this research has the potential to improve patient treatment. By leveraging my extensive expertise in neuroimmunology and collaborating with the host institute at the forefront of stroke-vascular biology research, I will also be able to contribute to the evolution of new ideas and expand my scientific horizons.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- social sciences sociology demography mortality
- natural sciences biological sciences genetics DNA
- medical and health sciences basic medicine physiology pathophysiology
- natural sciences physical sciences optics microscopy
- medical and health sciences basic medicine neurology stroke
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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(opens in new window) HORIZON-MSCA-2024-PF-01
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0313 Oslo
Norway
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