INFILTRATION OF INFLAMMATORY CELLS THROUGH BRAIN ENDOTHELIUM

The blood-brain barrier (BBB) restricts exchanges of soluble factors a nd cells between the blood and the brain, thus playing a crucial role in maintenance of cerebral homeostasis. It is composed of the endothel ial cells that line the cerebral capillaries. Cerebral capillaries hav e a number of distinctive morphological characteristics, including the presence of tight intercellular junctions. Also, the cerebral capilla ries are surrounded by astrocytic projections that exert a positive re gulatory effect on BBB tightness. One effect of the BBB is that the nu mber of leukocytes that patrol the central nervous system is far lower than in peripheral organs. Nevertheless, massive leukocyte infiltrati on occurs in some disease states: for instance, numerous activated leu kocytes are found in the cerebral parenchyma in patients with multiple sclerosis, and HIV encephalitis is probably due to passage of HIV-inf ected monocytes through the BBB. Compelling evidence has been obtained that the perivascular astrocytes and microglial cells, as well as the cerebral endothelial cells, locally produce inflammatory cytokines th at increase BBB permeability. Advances have also been made in the iden tification of leukocyte adhesion molecules expressed at the surface of cerebral endothelial cells. Expression of these molecules is induced by inflammatory cytokines. Interactions between these adhesion molecul es and their leukocyte ligands may induce modifications within endothe lial cells, including cytoskeleton reorganization and opening of inter cellular junctions, which may allow leukocytes to cross the BBB. It is to be hoped that the new insights gained into the mechanisms of leuko cyte penetration through the BBB may help to develop novel treatment s trategies for neuroinflammatory disorders.