Differential changes in junctional complex proteins suggest the ependymal lining as the main source of leukocyte infiltration into ventricles in murine neurocysticercosis.
The blood brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCB) limit the influx of immune mediators and bloodstream compounds into the central nervous system (CNS). Upon injury or infection, the integrity of these barriers is compromised and leukocyte infiltration occurs. The BCB is located in the choroid plexuses (CPs) found within ventricles of the brain, and it is considered one of the main routes of cellular infiltration into the CNS into healthy individuals. Our group recently showed that in a murine model of neurocysticercosis (NCC), there is a moderate increase in infiltration of leukocytes into ventricles, but the BCB is hardly compromised. To elucidate the role played by CPs and surrounding ependyma in leukocyte infiltration at ventricular sites, we analyzed changes in the expression of junctional complex proteins in animals intracranially infected with Mesocestoides corti. The results indicate that infection does not change the expression pattern of junctional complex proteins in CPs, but structural alterations and disappearance of these proteins were evident in ependyma adjacent to the internal leptomeninges. The kinetics and magnitude of these changes directly correlated with the extent of leukocyte infiltration through ependyma and with the expression and activity of MMPs. The results of this study indicate that the anatomical elements of the BCB are minimally disrupted during the course of murine NCC. Thus, most of the leukocytes infiltrating ventricles appear to extravasate through pial vessels located in the internal leptomeninges juxtaposed to the ependyma layer and then traverse the ependyma cells. In addition, MMP activity seems to be involved in this process. These results provide evidence for a previously undescribed entry route for leukocytes into the CNS.
Alvarez
Jorge I
JI
Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, TX 78249, USA.
Teale
Judy M
JM
D000818:Animals; D001927:Brain Diseases / Q000469:parasitology / Q000473:pathology*; D002590:Cestode Infections / Q000150:complications; D002831:Choroid Plexus / Q000469:parasitology / Q000503:physiopathology; D004195:Disease Models, Animal; D004805:Ependyma / Q000469:parasitology / Q000503:physiopathology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020019:Neurocysticercosis / Q000209:etiology / Q000469:parasitology / Q000473:pathology*
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins