concanavalin-a and Brain-Ischemia

Glycyrrhizin (Gly) protects against brain injury induced by stroke. We studied whether Gly achieves its protection by inhibiting T cell activity and high-mobility group box 1 (HMGB1) release in the ischemic brain.. Stroke was induced by transient middle cerebral artery occlusion in rats and mice. Gly was injected intraperitoneally before or after stroke. We measured infarction, neuroinflammatory cells, gene expressions of interferon-γ (IFNγ), IL-4, and IL-10 in CD4 T cells, HMGB1 release, and T cell proliferation in cultured splenocytes.. Gly treatment reduced infarctions and neuroinflammation characterized by the infiltration of CD68-positive macrophages and myeloperoxidase-positive neutrophils, which corresponds to a reduction in the number of T cells and their subsets, CD4 and CD8 T cells, in the ischemic brain, as measured by flow cytometry. Unlike in wild-type animals, Gly did not offer protection in nude rats and severe combined immunodeficient (SCID) mice who had no T cells, while Gly reduced infarction in both nude rats and SCID mice whose T cells were reconstituted, suggesting that T cells should be the target of Gly. In addition, Gly administration inhibited T cell proliferation stimulated by ConA in in vitro assays and inhibited HMGB1 release from the ischemic brain. Furthermore, Gly attenuated gene expression of IFNγ, but not IL-4 and IL-10 in CD4 T cells. Lastly, HMGB1 promoted T cell proliferation stimulated by ConA, which was inhibited by the addition of Gly.. Gly blocks infarction by inhibiting IFNγ-mediated T cell activity, which is at least partly modulated by HMGB1 activity.

Topics: Animals; Anti-Inflammatory Agents; Brain; Brain Infarction; Brain Ischemia; Cell Proliferation; Concanavalin A; Cytokines; Disease Models, Animal; Gene Expression Regulation; Glycyrrhizic Acid; HMGB1 Protein; Mice; Mice, Inbred C57BL; Mice, SCID; Phosphopyruvate Hydratase; Rats; Rats, Nude; Rats, Sprague-Dawley; T-Lymphocytes

Twenty two Mongolian gerbils after 5 min bilateral carotid artery occlusion and 6, 12, 24, 48, 72, 94 hours and 5 days survival were investigated for the neuronal changes in dorsal hippocampus. Paraffin sections were stained with cresyl-violet and marked by their binding of Concanavalin A (Con A) labelled with peroxidase. The degeneration and neuronal loss was observed only in CA1 sectors in almost all experimental groups, whereas the decreased binding of Con A by the neurons of CA1 sector corresponded to the intensity of histologic changes but appeared also only in this sector even without any histological changes. These observation can point at the subthreshold damage of CA1 neurons as result of either diminished supply or increased metabolism of d-glucose, or diminished number of Con A receptors or changes of their specificity after ischemic period.

Topics: Animals; Binding Sites; Brain Ischemia; Concanavalin A; Gerbillinae; Hippocampus; Neurons