4.2 Article

Evaluation of the effects of a new drug on brain leukocyte infiltration in an experimental model of autoimmune encephalomyelitis

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LETTERS IN DRUG DESIGN & DISCOVERY
卷 3, 期 3, 页码 138-148

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BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/157018006776286943

关键词

GEM-SP drug; leukocyte infiltration; experimental autoimmune encephalomyelitis (EAE); blood brain barrier (BBB); multiple sclerosis (MS); immunohistochemistry; autoimmunity; immunomodulator; pan-leukocyte marker (anti-CD 45)

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Experimental Autoimmune Encephalomyelitis (EAE) was induced for the evaluation of a new drug candidate (GEM-SP) for multiple sclerosis. Using immunocytochemical techniques with a pan-leukocyte marker, anti-CD 45, differential leukocyte infiltration was compared in different experimental groups: 1) EAE-immunized rats treated with GEM-SP; 2) EAE-immunized rats treated with NaCl; 3) EAE-immunized rats treated with free constituents (not linked to inert carrier protein) and the inert carrier protein of GEM-SP. The results were conclusive: a very high degree of infiltration was observed in groups 2 and 3. Compared with these, group I showed a very poor leukocyte infiltration. Thus, the effect of GEM-SP against leukocyte infiltration was very strong, suggesting a decrease of the blood brain barrier permeability. Moreover, the same composition of GEM-SP (non-linked) was poorly active against leukocyte infiltration. The effect of GEM-SP therefore on the blood brain barrier appears to be very effective, rendering it less permeable to leukocyte infiltration and decreasing leukocyte infiltration per se and/or it is also possible that GEM-SP could play an immunomodulator role. The present results suggest GEM-SP as a new potential drug candidate for the treatment of multiple sclerosis.

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