Beta-amyloid peptide-induced blood-brain barrier disruption facilitates T-cell entry into the rat brain

Ibolya G. Farkas, Andrea Czigner, Eszter Farkas, Endre Dobó, Katalin Soós, Botond Penke, Valéria Endrész, Andrés Mihály

Research output: Contribution to journalArticle

40 Citations (Scopus)

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 (Aβ) or tumor necrosis factor-alpha (TNFα) 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 (Aβ or TNFα) TNF(X) 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 Aβ and TNFα 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.

Original languageEnglish
Pages (from-to)115-125
Number of pages11
JournalActa histochemica
Volume105
Issue number2
DOIs
Publication statusPublished - Jan 1 2003

Keywords

  • Beta-amyloid peptide
  • Blood-brain barrier
  • Central nervous system
  • T-lymphocyte
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Histology
  • Cell Biology

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