ABSTRACT
Infl ammatory responses in the central nervous system (CNS) are fundamentally different from other organs due to the unique structure and function of brain endothelial cells (EC) and the specialized properties of resident CNS cells. Under normal conditions, the intact blood-brain barrier (BBB) restricts the infl ux of hematogenous cells from blood into brain, thus tightly regulating the potential for immune intervention. In the initial stages and during the evolution of infectious, infl ammatory processes, ischemia and trauma, various classes of leukocytes migrate across the BBB and accumulate in the brain at sites of tissue injury, microbial pathogens or in response to CNS antigens. Since cerebral EC are the site of the initial contact with circulating leukocytes, molecular interactions between them are of paramount importance for the recruitment of leukocytes across the BBB and the initiation and maintenance of immune responses. These interactions are specifi c and involve cross talk between endothelial surface molecules and corresponding receptors on leukocytes which set the stage for immune cell entry into the brain. An important concept that has emerged from several studies is that activation of the endothelium is a key event in the regulation of leukocyte extravasation. Cytokines released peripherally or produced locally by activated leukocytes, microglial cells or astrocytes induce profound, mostly reversible and variably lasting functional and morphological alterations on cerebral EC which are associated with the expression of a host of surface antigens, synthesis and release of
1 Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver General Hospital, 855 West 12th Avenue, Vancouver, Canada, V5Z-1M9.
