title: Region-specific permeability of the blood-brain barrier upon pericyte loss.
abstract: The blood-brain barrier (BBB) regulates differing needs of the various brain regions by controlling transport of blood-borne components from the neurovascular circulation into the brain parenchyma. The mechanisms underlying region-specific transport across the BBB are not completely understood. Previous work showed that pericytes are key regulators of BBB function. Here we investigated whether pericytes influence BBB permeability in a region-specific manner by analysing the regional permeability of the BBB in the pdgf-bret/retmouse model of pericyte depletion. We show that BBB permeability is heterogeneous in pdgf-bret/retmice, being significantly higher in the cortex, striatum and hippocampus compared to the interbrain and midbrain. However, we show that this regional heterogeneity in BBB permeability is not explained by local differences in pericyte coverage. Region-specific differences in permeability were not associated with disruption of tight junctions but may result from changes in transcytosis across brain endothelial cells. Our data show that certain brain regions are able to maintain low BBB permeability despite substantial pericyte loss and suggest that additional, locally-acting mechanisms may contribute to control of transport.
authors.affiliation: 1 Roche Pharma Research and Early Development (pRED), Neurodegeneration and Regeneration, Roche Innovation Center Basel, Switzerland.
authors.forename: Roberto
authors.initials: R
authors.lastname: Villaseñor
authors.affiliation: 2 Roche Pharma Research and Early Development (pRED), Translational Medicine Neuroscience & Biomarkers, Roche Innovation Center Basel, Switzerland.
authors.forename: Basil
authors.initials: B
authors.lastname: Kuennecke
authors.affiliation: 1 Roche Pharma Research and Early Development (pRED), Neurodegeneration and Regeneration, Roche Innovation Center Basel, Switzerland.
authors.forename: Laurence
authors.initials: L
authors.lastname: Ozmen
authors.affiliation: 1 Roche Pharma Research and Early Development (pRED), Neurodegeneration and Regeneration, Roche Innovation Center Basel, Switzerland.
authors.forename: Michelle
authors.initials: M
authors.lastname: Ammann
authors.affiliation: 1 Roche Pharma Research and Early Development (pRED), Neurodegeneration and Regeneration, Roche Innovation Center Basel, Switzerland.
authors.forename: Christof
authors.initials: C
authors.lastname: Kugler
authors.affiliation: 1 Roche Pharma Research and Early Development (pRED), Neurodegeneration and Regeneration, Roche Innovation Center Basel, Switzerland.
authors.forename: Fiona
authors.initials: F
authors.lastname: Grüninger
authors.affiliation: 1 Roche Pharma Research and Early Development (pRED), Neurodegeneration and Regeneration, Roche Innovation Center Basel, Switzerland.
authors.forename: Hansruedi
authors.initials: H
authors.lastname: Loetscher
authors.affiliation: 1 Roche Pharma Research and Early Development (pRED), Neurodegeneration and Regeneration, Roche Innovation Center Basel, Switzerland.
authors.forename: Per-Ola
authors.initials: PO
authors.lastname: Freskgård
authors.affiliation: 1 Roche Pharma Research and Early Development (pRED), Neurodegeneration and Regeneration, Roche Innovation Center Basel, Switzerland.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Collin
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology / Q000378:metabolism*; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D002199:Capillary Permeability; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D051379:Mice; D020286:Pericytes / Q000166:cytology / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism
chemical_list: D007074:Immunoglobulin G
keywords: Blood–brain barrier; extravasation; neurovascular unit; pericytes; permeability