Inflammatory mediators of cerebral endothelium: A role in ischemic brain inflammation

Brain inflammation has been implicated in the development of brain edema an d secondary brain damage in ischemia and trauma, Adhesion molecules, cytoki nes and leukocyte chemoattractants released/presented at the site of blood- brain barrier (BBB) play an important role in mobilizing peripheral inflamm atory cells into the brain, Cerebral endothelial cells (CEC) are actively e ngaged in processes of microvascular stasis and leukocyte infiltration by p roducing a plethora of pro-inflammatory mediators, When challenged by exter nal stimuli including cytokines and hypoxia, CEC have been shown to release /express various products of arachidonic acid cascade with both vasoactive and pro-inflammatory properties, including prostaglandins, leukotrienes, an d platelet-activating factor (PAF), These metabolites induce platelet and n eutrophil activation and adhesion, changes in local cerebral blood flow and blood rheology, and increases in BBB permeability. Ischemic CEC have also been shown to express and release bioactive inflammatory cytokines and chem okines, including IL-1 beta, IL-8 and MCP-1, Many of these mediators and is chemia in vitro and in vivo have been shown to upregulate the expression of both selectin and Ig-families of adhesion molecules in CEC and to facilita te leukocyte adhesion and transmigration into the brain, Collectively, thes e studies demonstrate a pivotal role of CEC in initiating and regulating in flammatory responses in cerebral ischemia.