PMID- 29935189 OWN - NLM STAT- MEDLINE DCOM- 20190411 LR - 20190411 IS - 1879-3185 (Electronic) IS - 0300-483X (Linking) VI - 408 DP - 2018 Sep 1 TI - Ultrastructural and biochemical features of cerebral microvessels of adult rat subjected to a low dose of silver nanoparticles. PG - 31-38 LID - S0300-483X(18)30121-5 [pii] LID - 10.1016/j.tox.2018.06.009 [doi] AB - The widespread use of silver nanoparticles (AgNPs) in medicine and in multiple commercial products has motivated researchers to investigate their potentially hazardous effects in organisms. Since AgNPs may easily enter the brain through the blood-brain barrier (BBB), characterization of their interactions with cellular components of the neurovascular unit (NVU) is of particular importance. Therefore, in an animal model of prolonged low-dose exposure, we investigate the extent and mechanisms of influence of AgNPs on cerebral microvessels. Adult rats were treated orally with small (10 nm) AgNPs in a dose of 0.2 mg/kg b.w. over a 2-week period. A silver citrate-exposed group was established as a positive control of ionic silver effects. Alterations in the expression of tight junction proteins claudin-5, ZO-1, and occludin, were observed. These effects are accompanied by ultrastructural features indicating enhanced permeability of microvessels such as focal edema of perivascular astrocytic processes and surrounding neuropil. We did not identify changes in the expression of PDGFbetaR which is a marker of pericytes. Ultrastructural alterations in these cells were not identified. The results show that altered integrity of cerebral vessels under a low-dose of AgNP-exposure may be the consequence of dysfunction of endothelial cells caused by disruption of tight junction proteins. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Dabrowska-Bouta, Beata AU - Dabrowska-Bouta B AD - Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego str., 02-106 Warsaw, Poland. FAU - Sulkowski, Grzegorz AU - Sulkowski G AD - Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego str., 02-106 Warsaw, Poland. FAU - Frontczak-Baniewicz, Malgorzata AU - Frontczak-Baniewicz M AD - Electron Microscopy Platform, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego str., 02-106 Warsaw, Poland. FAU - Skalska, Joanna AU - Skalska J AD - Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego str., 02-106 Warsaw, Poland. FAU - Salek, Mikolaj AU - Salek M AD - Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego str., 02-106 Warsaw, Poland. FAU - Orzelska-Gorka, Jolanta AU - Orzelska-Gorka J AD - Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4a Chodzki str., 20-093 Lublin, Poland. FAU - Struzynska, Lidia AU - Struzynska L AD - Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego str., 02-106 Warsaw, Poland. Electronic address: lidkas@imdik.pan.pl. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180620 PL - Ireland TA - Toxicology JT - Toxicology JID - 0361055 RN - 0 (Citrates) RN - 0 (Claudin-5) RN - 0 (Cldn5 protein, rat) RN - 0 (Occludin) RN - 0 (Ocln protein, rat) RN - 0 (Silver Compounds) RN - 0 (Tjp1 protein, rat) RN - 0 (Zonula Occludens-1 Protein) RN - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta) SB - IM MH - Administration, Oral MH - Animals MH - Brain/*blood supply MH - Capillaries/*drug effects/metabolism/ultrastructure MH - Capillary Permeability/drug effects MH - Citrates/administration & dosage/*toxicity MH - Claudin-5/genetics/metabolism MH - Dose-Response Relationship, Drug MH - Male MH - Metal Nanoparticles/*toxicity MH - Occludin/genetics/metabolism MH - Particle Size MH - Rats, Wistar MH - Receptor, Platelet-Derived Growth Factor beta/genetics/metabolism MH - Silver Compounds/administration & dosage/*toxicity MH - Tight Junctions/drug effects/metabolism/ultrastructure MH - Time Factors MH - Zonula Occludens-1 Protein/genetics/metabolism OTO - NOTNLM OT - Blood-brain barrier OT - Nanosilver OT - Nanotoxicity OT - Occludin OT - Tight junction proteins OT - ZO-1 OT - claudin-5 EDAT- 2018/06/24 06:00 MHDA- 2019/04/12 06:00 CRDT- 2018/06/24 06:00 PHST- 2018/01/08 00:00 [received] PHST- 2018/06/15 00:00 [revised] PHST- 2018/06/19 00:00 [accepted] PHST- 2018/06/24 06:00 [pubmed] PHST- 2019/04/12 06:00 [medline] PHST- 2018/06/24 06:00 [entrez] AID - S0300-483X(18)30121-5 [pii] AID - 10.1016/j.tox.2018.06.009 [doi] PST - ppublish SO - Toxicology. 2018 Sep 1;408:31-38. doi: 10.1016/j.tox.2018.06.009. Epub 2018 Jun 20.