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 language | English |
|---|---|
| Pages (from-to) | 991-1001 |
| Number of pages | 11 |
| Journal | Journal of NeuroImmune Pharmacology |
| Volume | 7 |
| Issue number | 4 |
| DOIs | |
| State | Published - Dec 1 2012 |
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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 journal › Article
}
TY - JOUR
T1 - Cerebrovascular toxicity of PCB153 is enhanced by binding to silica nanoparticles
AU - Zhang, Bei
AU - Chen, Lei
AU - Choi, Jeong June
AU - Hennig, Bernhard
AU - Toborek, Michal J
PY - 2012/12/1
Y1 - 2012/12/1
N2 - 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.
AB - 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.
KW - Blood-brain barrier
KW - Polychlorinated biphenyls
KW - Silica nanoparticles
KW - Stroke
KW - Tight junctions
UR - http://www.scopus.com/inward/record.url?scp=84875872800&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875872800&partnerID=8YFLogxK
U2 - 10.1007/s11481-012-9403-y
DO - 10.1007/s11481-012-9403-y
M3 - Article
C2 - 23081707
AN - SCOPUS:84875872800
VL - 7
SP - 991
EP - 1001
JO - Journal of NeuroImmune Pharmacology
JF - Journal of NeuroImmune Pharmacology
SN - 1557-1890
IS - 4
ER -