The immunomodulatory sphingosine 1-phosphate analog FTY720 reduces lesion size and improves neurological outcome in a mouse model of cerebral ischemia

Czech, Bozena; Pfeilschifter, Waltraud; Mazaheri-Omrani, Niloufar; Strobel, Marc André; Kahles, Timo; Neumann-Haefelin, Tobias; Rami, Abdelhaq; Huwiler, Andrea; Pfeilschifter, Josef (2009). The immunomodulatory sphingosine 1-phosphate analog FTY720 reduces lesion size and improves neurological outcome in a mouse model of cerebral ischemia. Biochemical and biophysical research communications, 389(2), pp. 251-6. Orlando, Fla.: Academic Press 10.1016/j.bbrc.2009.08.142

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Cerebral ischemia is accompanied by fulminant cellular and humoral inflammatory changes in the brain which contribute to lesion development after stroke. A tight interplay between the brain and the peripheral immune system leads to a biphasic immune response to stroke consisting of an early activation of peripheral immune cells with massive production of proinflammatory cytokines followed by a systemic immunosuppression within days of cerebral ischemia that is characterized by massive immune cell loss in spleen and thymus. Recent work has documented the importance of T lymphocytes in the early exacerbation of ischemic injury. The lipid signaling mediator sphingosine 1-phosphate-derived stable analog FTY720 (fingolimod) acts as an immunosuppressant and induces lymphopenia by preventing the egress of lymphocytes, especially T cells, from lymph nodes. We found that treatment with FTY720 (1mg/kg) reduced lesion size and improved neurological function after experimental stroke in mice, decreased the numbers of infiltrating neutrophils, activated microglia/macrophages in the ischemic lesion and reduced immunohistochemical features of apoptotic cell death in the lesion.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Huwiler, Andrea

ISSN:

0006-291X

Publisher:

Academic Press

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:10

Last Modified:

04 May 2014 23:22

Publisher DOI:

10.1016/j.bbrc.2009.08.142

PubMed ID:

19720050

Web of Science ID:

000270764400009

URI:

https://boris.unibe.ch/id/eprint/30672 (FactScience: 194936)

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