Analysis of leukocyte extravasation across the blood-brain barrier: conceptual and technical aspects

The central nervous system (CNS) has long been described as an immunologically privileged organ. However, evidence is accumulating that the CNS is more adequately described as immune competent, albeit atypical. Leukocyte trafficking into the CNS in response to inflammation, as in peripheral organs, occurs in several distinct steps. As with all leukocyte trafficking, the overall process is governed in part by chemokines. The CNS has unique anatomic and physiologic attributes, including the blood-brain barrier. These characteristic features of the CNS interact with a distinct array of chemokines, expressed both constitutively and in response to inflammation. In this review, we consider the potential sites of chemokine action in guiding leukocyte migration. The process of extravasation can usefully be regarded as comprising individual steps. This review is focused on the need to consider these stages separately, and the elucidation of mechanisms at each stage is outlined.