Cerebrovascular toxicity of PCB153 is enhanced by binding to silica nanoparticles

Bei Zhang, Lei Chen, Jeong June Choi, Bernhard Hennig, Michal J Toborek

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Environmental polychlorinated biphenyls (PCBs) are frequently bound onto nanoparticles (NPs). However, the toxicity and health effects of PCBs assembled onto nanoparticles are unknown. The aim of this study was to study the hypothesis that binding PCBs to silica NPs potentiates PCB-induced cerebrovascular toxicity and brain damage in an experimental stroke model. Mice (C57BL/6, males, 12-week-old) were exposed to PCB153 bound to NPs (PCB153-NPs), PCB153, or vehicle. PCB153 was administered in the amount of 5 ng/g body weight. A group of treated animals was subjected to a 40 min ischemia, followed by a 24 h reperfusion. The blood-brain barrier (BBB) permeability, brain infarct volume, expression of tight junction (TJ) proteins, and inflammatory mediators were assessed. As compared to controls, a 24 h exposure to PCB153-NPs injected into cerebral vasculature resulted in significant elevation of the BBB permeability, disruption of TJ protein expression, increased proinflammatory responses, and enhanced monocyte transmigration in mouse brain capillaries. Importantly, exposure to PCB153-NPs increased stroke volume and potentiated brain damage in mice subjected to ischemia/reperfusion. A long-term (30 days) oral exposure to PCB153-NPs resulted in a higher PCB153 content in the abdominal adipose tissue and amplified adhesion of leukocytes to the brain endothelium as compared to treatment with PCB153 alone. This study provides the first evidence that binding to NPs increases cerebrovascular toxicity of environmental toxicants, such as PCB153.

Original languageEnglish
Pages (from-to)991-1001
Number of pages11
JournalJournal of NeuroImmune Pharmacology
Volume7
Issue number4
DOIs
StatePublished - Dec 1 2012

Fingerprint

Silicon Dioxide
Nanoparticles
Polychlorinated Biphenyls
Brain
Tight Junction Proteins
Blood-Brain Barrier
Reperfusion
Permeability
Ischemia
Tissue Adhesions
Abdominal Fat
Inbred C57BL Mouse
Stroke Volume
Endothelium
Monocytes
Leukocytes
Theoretical Models
Stroke
Body Weight
Health

Keywords

  • Blood-brain barrier
  • Polychlorinated biphenyls
  • Silica nanoparticles
  • Stroke
  • Tight junctions

ASJC Scopus subject areas

  • Pharmacology
  • Immunology and Allergy
  • Immunology
  • Neuroscience (miscellaneous)

Cite this

Cerebrovascular toxicity of PCB153 is enhanced by binding to silica nanoparticles. / Zhang, Bei; Chen, Lei; Choi, Jeong June; Hennig, Bernhard; Toborek, Michal J.

In: Journal of NeuroImmune Pharmacology, Vol. 7, No. 4, 01.12.2012, p. 991-1001.

Research output: Contribution to journalArticle

Zhang, Bei ; Chen, Lei ; Choi, Jeong June ; Hennig, Bernhard ; Toborek, Michal J. / Cerebrovascular toxicity of PCB153 is enhanced by binding to silica nanoparticles. In: Journal of NeuroImmune Pharmacology. 2012 ; Vol. 7, No. 4. pp. 991-1001.
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