Objective
Multiple sclerosis (MS) is a largely Th1-mediated disease of central nervous system (CNS). Pro-inflammatory cytokines exert a pivotal role in this pathophysiology. However, their cellular origin and the causes of variation of their brain levels are still obscured. In addition, the relapse and remission phases in MS are related to peripheral infections. This project aims to analyze how a peripheral infection influences cytokine synthesis in a brain Th1 mediated immune reaction and at what extent greater synthesis of pro-inflammatory cytokines may exacerbate tissue injury at the focus of the lesion and distal to lesion. Perry's model of CNS inflammation will be used. It consists of a Bacillus Calmette-Guérin (BCG) priming in the CNS, followed by a subcutaneous injection of BCG, which induces a Th1 delayed type hypersensitivity(DTH) response at the primary site of injection in the parenchyma brain. Brain lesions induced by sensitization to BCG are chronic and show histopathological features that are similar to those of MS. These research objectives will be investigated:
(1) the cytokine expression in a brain Th1 DTH
(2) the cytokine expression at sites distal to the primary Th1 lesion. In both cases, it will be studied how the levels of cytokines are modified by an acute peripheral infection
(3) the assessment of the increase in the tissue damage insofar as the cytokine production is enhanced at these sites. These changes will be studied by Magnetic Resonance Imaging analysis.
Expression of mRNAs and production of pro- and anti-inflammatory cytokines will be measured in the site of DTH lesions and distal regions, one and two months after the subcutaneous challenge. Cytokine expression in animals that have been challenged peripherally with endotoxin or IL-1-adenovirus will be investigated at selected time intervals. I will use state-of-the-art in vivo biology, cell biology and molecular techniques such as immunocytochemistry, co focal microscopy, western blotting and quantitative competitive PCR. In addition, I will use non-invasive methods to monitor degenerative disease by behavioral measures, magnetic resonance imaging and spectroscopy of small animals and then will gain expertise in all these methods. To date, I have studied the role of peripheral inflammation on cytokine synthesis in the brain. My skill will contribute to explore the peripheral-central interactions may worsen pathology such as Multiple Sclerosis.
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.
- natural sciences biological sciences neurobiology
- medical and health sciences basic medicine physiology pathophysiology
- medical and health sciences basic medicine neurology multiple sclerosis
- medical and health sciences basic medicine pathology
- engineering and technology medical engineering diagnostic imaging magnetic resonance imaging
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
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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.
Coordinator
SO16 7PX SOUTHAMPTON
United Kingdom
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.