title: Blood-brain barrier impairment in an animal model of MPS III B.
abstract: BACKGROUND
  Sanfilippo syndrome type B (MPS III B) is caused by a deficiency of α-N-acetylglucosaminidase enzyme, leading to accumulation of heparan sulfate within lysosomes and eventual progressive cerebral and systemic multiple organ abnormalities. However, little is known about the competence of the blood-brain barrier (BBB) in MPS III B. BBB dysfunction in this devastating disorder could contribute to neuropathological disease manifestations.
  
  
  RESULTS
  In the present study, we investigated structural (electron microscope) and functional (vascular leakage) integrity of the BBB in a mouse model of MPS III B at different stages of disease, focusing on brain structures known to experience neuropathological changes. Major findings of our study were: (1) endothelial cell damage in capillary ultrastructure, compromising the BBB and resulting in vascular leakage, (2) formation of numerous large vacuoles in endothelial cells and perivascular cells (pericytes and perivascular macrophages) in the large majority of vessels, (3) edematous space around microvessels, (4) microaneurysm adjacent to a ruptured endothelium, (6) Evans Blue and albumin microvascular leakage in various brain structures, (7) GM3 ganglioside accumulation in endothelium of the brain microvasculature.
  
  
  CONCLUSIONS
  These new findings of BBB structural and function impairment in MPS III B mice even at early disease stage may have implications for disease pathogenesis and should be considered in current and future development of treatments for MPS III B.
authors.affiliation: College of Medicine, Center of Excellence for Aging & Brain Repair, University of South Florida, Tampa, Florida, United States of America. sgarbuzo@health.usf.edu
authors.forename: Svitlana
authors.initials: S
authors.lastname: Garbuzova-Davis
authors.forename: Michael K
authors.initials: MK
authors.lastname: Louis
authors.forename: Edward M
authors.initials: EM
authors.lastname: Haller
authors.forename: Hiranya M
authors.initials: HM
authors.lastname: Derasari
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Rawls
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sanberg
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000418:Albumins / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D005070:Evans Blue / Q000378:metabolism; D005679:G(M3) Ganglioside / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D055806:Microvessels / Q000473:pathology / Q000648:ultrastructure; D009084:Mucopolysaccharidosis III / Q000201:enzymology / Q000473:pathology
chemical_list: D000418:Albumins; D005679:G(M3) Ganglioside; D005070:Evans Blue; C033079:alpha-N-acetyl-D-glucosaminidase; D000118:Acetylglucosaminidase