Effect of lipopolysaccharide on the permeability and reactivity of the cerebral microcirculation: role of inducible nitric oxide synthase

doi:10.1016/S0006-8993(98)00259-5

Brain Research

Volume 792, Issue 2, 11 May 1998, Pages 353-357

https://doi.org/10.1016/S0006-8993(98)00259-5 Get rights and content

Abstract

The goal of this study was to examine the effect of lipopolysaccharide on the permeability of the blood–brain barrier and reactivity of cerebral arterioles. We examined the pial microcirculation in rats using intravital fluorescence microscopy. Permeability of the blood–brain barrier (clearance of fluorescent-labeled dextran; molecular weight 10,000 Da; FITC-dextran-10K) and diameter of pial arterioles were measured in the absence and presence of topical application of vehicle (saline) or lipopolysaccharide (200 ng/ml). During superfusion with vehicle, clearance of FITC-dextran-10K from pial vessels was minimal, and diameter of pial arterioles remained constant. Topical application of lipopolysaccharide (200 ng/ml) produced an increase in clearance of FITC-dextran-10K and dilated pial arterioles. To determine whether lipopolysaccharide-induced changes in permeability of the blood–brain barrier and dilatation of cerebral arterioles was related to the synthesis/release of inducible nitric oxide, we examined the effects of aminoguanidine (0.5 mM). Aminoguanidine inhibited lipopolysaccharide-induced increases in permeability of the blood–brain barrier and dilatation of cerebral arterioles. The findings of the present study suggest that lipopolysaccharide increases permeability of the blood–brain barrier and diameter of pial arterioles via the activation of inducible nitric oxide synthase.

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Acknowledgements

This study was supported by a National Heart, Lung, and Blood Institute Grant (HL-40781), a grant from the Smokeless Tobacco Research Council (0668-01), a Grant-in-Aid from the American Heart Association; Nebraska Affiliate (9607851S), a Grant-in-Aid from the American Diabetes Association, a Grant-in-Aid from the American Heart Association; National Affiliate (96006160) and support from the University of Nebraska Medical Center.

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APC treatment significantly improves pial microcirculation by reducing leukocyte adhesion and increasing FCD.
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Short communicationEffect of lipopolysaccharide on the permeability and reactivity of the cerebral microcirculation: role of inducible nitric oxide synthase

Abstract

Section snippets

Acknowledgements

Brain Res.

Neurosci. Lett.

Brain Res.

TINS

Cerebrovascular permeability changes during experimental meningitis in the rat

J. Pharmacol. Exp. Ther.

Dilatation of cerebral arterioles in response to lipopolysaccharide in vivo

Stroke

Mechanisms of endotoxin-induced dilatation of cerebral arterioles

Am. J. Physiol.

Effect of endotoxin on permeability of bovine cerebral endothelial cell layers in vitro

J. Pharmacol. Exp. Ther.

Disruption of the blood–brain barrier in cerebrum and brainstem during acute hypertension

Am. J. Physiol.

Permeability of blood–brain barrier to various sized molecules

Am. J. Physiol.

Short communication
Effect of lipopolysaccharide on the permeability and reactivity of the cerebral microcirculation: role of inducible nitric oxide synthase