Modulation of brain inflammation by peripheral immune stimuli in an animal model of multiple sclerosis

Cel

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.

Dziedzina nauki (EuroSciVoc)

Klasyfikacja projektów w serwisie CORDIS opiera się na wielojęzycznej taksonomii EuroSciVoc, obejmującej wszystkie dziedziny nauki, w oparciu o półautomatyczny proces bazujący na technikach przetwarzania języka naturalnego. Więcej informacji: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc

Program(-y)

FP5-HUMAN POTENTIAL - Programme for research, technological development and demonstration on "Improving the human research potential and the socio-economic knowledge base" (1998-2002)

Temat(-y)

Data not available

Zaproszenie do składania wniosków

Data not available

System finansowania

RGI - Research grants (individual fellowships)

Koordynator

UNIVERSITY OF SOUTHAMPTON

Wkład UE

Brak danych

Adres

Bassett Crescent East
SO16 7PX SOUTHAMPTON
Zjednoczone Królestwo

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