title: Beta-amyloid peptide-induced blood-brain barrier disruption facilitates T-cell entry into the rat brain.
abstract: Activated T-lymphocytes can migrate through the blood-brain barrier (BBB) and are able to invade the central nervous system (CNS). In the present study, we investigated whether disruption of the BBB leads to enhanced T-cell migration into the CNS. Amyloid-beta peptide 25-35 (A beta) or tumor necrosis factor-alpha (TNFalpha) were administered into the right common carotid artery of adult male Wistar rats. The agents were administered either alone, or were followed by a cell suspension of exogenously activated T-cells. Rats of other groups received activated or non-stimulated T-lymphocytes only. Sagittal brain sections were analyzed with immunohistochemistry of CD3 to reveal the presence of T-lymphocytes within the CNS parenchyma. Administration of activated T-cells alone led to T-cell migration into the brain. Infusion of either substances (A beta or TNFalpha) resulted in T-cell invasion of the CNS even when no exogenous T-cells were added. Infusion of either of the agents together with T-lymphocytes generated a more intense T-lymphocyte migration than in the other groups. Electron microscopic analysis and Evans-blue extravasation studies confirmed parallel disruption of the BBB. Our study demonstrates that A beta and TNFalpha induce enhanced T-lymphocyte migration towards the brain. This effect may be attributed at least partly to dysfunctioning of the BBB, but other mechanisms are also possible.
authors.affiliation: Department of Anatomy, Histology and Embryology, University of Szeged, Hungary. farkasi@anat-fm.szote.u-szeged.hu
authors.forename: Ibolya G
authors.initials: IG
authors.lastname: Farkas
authors.forename: Andrea
authors.initials: A
authors.lastname: Czigner
authors.forename: Eszter
authors.initials: E
authors.lastname: Farkas
authors.forename: Endre
authors.initials: E
authors.lastname: Dobó
authors.forename: Katalin
authors.initials: K
authors.lastname: Soós
authors.forename: Botond
authors.initials: B
authors.lastname: Penke
authors.forename: Valéria
authors.initials: V
authors.lastname: Endrész
authors.forename: András
authors.initials: A
authors.lastname: Mihály
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000648:ultrastructure; D017252:CD3 Complex / Q000032:analysis; D002490:Central Nervous System / Q000276:immunology; D005070:Evans Blue; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000494:pharmacology* / Q000633:toxicity; D010835:Phytohemagglutinins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D017252:CD3 Complex; D010446:Peptide Fragments; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; C074636:amyloid beta-protein (25-35); D005070:Evans Blue