title: Immunogold study of effects of prenatal exposure to lipopolysaccharide and/or valproic acid on the rat blood-brain barrier vessels.
abstract: The involvement of blood microvessels, representing the anatomic site of the blood-brain barrier (BBB), in brain damage induced by prenatal exposure to lipopolysaccharide (LPS) and/or valproic acid (VPA) was studied in four-week-old rats. The immunogold procedure was applied for localization at the ultrastructural level of endogenous albumin and glucose transporter (GLUT-1) in three brain regions: cerebral cortex, cerebellum and hippocampus. Four groups of rats were used: (1) untreated control, (2) prenatally VPA-treated, (3) prenatally LPS-treated, and (4) prenatally LPS- and VPA-treated. The functional state of the BBB was evaluated as follows: (a) by its tightness, i.e., permeability to blood-borne albumin, and (b) by the expression of GLUT-1 in the endothelial cells (ECs). Using morphometry, the labelling density for GLUT-1 was recorded over luminal and abluminal plasma membranes of the ECs, also providing information on their functional polarity. No extensive increase of vascular permeability and/or any considerable dysfunction of the BBB in experimental groups nos. 2 and 3 were observed, although in solitary vascular profiles, increased endocytosis or even transcytosis of albumin by ECs was noted. In experimental group no. 4, some vascular profiles showed scanty leakage (microleakage), manifested by the presence of immunosignals for albumin in the perivascular area. Although some fluctuations in the expression of GLUT-1 occurred in all experimental groups, especially in group no. 3, a most pronounced and significant diminution of the labelling density, in all three regions of the brain, was observed in group no. 4. This finding suggests the synergistic action of prenatally applied LPS and VPA that affects specific transport functions of glucose in the microvascular endothelium. The diminished or disturbed supply of glucose to selected brain regions can be one of the factors leading to previously observed behavioral disturbances in similarly treated rats.
authors.affiliation: New York State Office of Mental Retardation and Developmental Disabilities, Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Vorbrodt
authors.forename: D H
authors.initials: DH
authors.lastname: Dobrogowska
authors.forename: P B
authors.initials: PB
authors.lastname: Kozlowski
authors.forename: A
authors.initials: A
authors.lastname: Rabe
authors.forename: M
authors.initials: M
authors.lastname: Tarnawski
authors.forename: M H
authors.initials: MH
authors.lastname: Lee
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002648:Child; D002658:Developmental Disabilities / Q000378:metabolism / Q000503:physiopathology; D004357:Drug Synergism; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000633:toxicity; D005260:Female; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008607:Intellectual Disability / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008833:Microcirculation / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D046529:Microscopy, Electron, Transmission; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans; D014635:Valproic Acid / Q000633:toxicity*
chemical_list: D000418:Albumins; D004791:Enzyme Inhibitors; D051272:Glucose Transporter Type 1; D008070:Lipopolysaccharides; D014635:Valproic Acid; D005947:Glucose