Breakdown of the blood brain barrier and blood-cerebrospinal fluid barrier is associated with differential leukocyte migration in distinct compartments of the CNS during the course of murine NCC

Brain homeostasis is normally protected by the blood brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCB), barriers that function in distinct CNS compartments and consist of different types of blood vessels including pial (subarachnoid spaces, leptomeninges), parenchymal (cerebral cortex) and ventricular vessels. In this study, a mouse model of neurocysticercosis was used to distinguish between changes in the permeability of the BBB and the BCB and determine the association of such alterations on leukocyte infiltration. Mice were intracranially infected with the parasite Mesocestoides corti and sacrificed at various times post infection. Different anatomical areas of infected brain were analyzed by three color immunofluoresence utilizing antibodies against serum proteins to assess brain barrier permeability, glial fibrillary acidic protein (GFAP) to detect astrocytes, and specific cell surface markers to determine the subpopulations of leukocytes infiltrating the CNS at particular sites. The results indicate increased permeability of all three types of vessels/structural sites as a result of infection evidenced by serum proteins and leukocyte extravasation but with considerable differences in the timing and extent of these permeability changes. Parenchymal vessels were the most resilient to changes in permeability whereas pial vessels were the least. Choroid plexus vessels of the ventricles also appeared less susceptible to increased permeability compared with pial vessels. In addition, parenchymal vessels appeared impermeable to particular types of immune cells even after extended periods of infection. Additionally, alterations in reactive astrocytes juxtaposed to blood vessels that exhibited increased permeability displayed increased expression of cytokines known to regulate brain barrier function. The results suggest that access of leukocytes and serum derived factors into the infected brain depend on several parameters including the anatomical area, type of vascular bed, cell phenotype and cytokine microenvironment.