Perillyl alcohol (POH) prevents ECM development, and that its potential mechanism of action can be by controlling the excessive immune response, downregulating the proinflammatory cytokines secretion in the spleen and brain. Also, we suggested that POH treatment may have a direct effect on the vascular endothelium activation , since we found that there was a significant improvement in the blood-brain barrier breakdown and that several endothelial receptors, such as, ICAM-1 e VCAM-1, were downregulated,. thus, a decreasing the parasite accumulation in the brain. Indeed, a benefical effect of POH on endothelial activation has also been demonstrated in in vitro models. Human brain endothelial cells were co-cultured with POH, and we found a significant decrease in vascular permeability of POH-treated cells. Based on the results obtained up to this phase of the project, and given the major roles played by MV in CM pathogenesis, we asked whether POH action in ECM might be related to the inhibition of MV production and MV activation of endothelial cells.
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