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      Clearance of [ 125I]-Tumor Necrosis Factor-α from the Brain into the Blood after Intracerebroventricular Injection in Rats

      ,

      Neuroimmunomodulation

      S. Karger AG

      Cytokine, Brain, Tumor necrosis factor-alpha

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          Abstract

          To test the hypothesis that brain to blood clearance is a mechanism by which brain inflammation and damage can increase circulating acute phase cytokines, rate of transfer of [<sup>125</sup>I]-tumor necrosis factor-α ([<sup>125</sup>I]-TNF) from brain to blood was determined. Acid precipitable [<sup>125</sup>I]-TNF appeared in peripheral blood within 5 min of intracerebroventricular (i.c.v.) injection and was cleared from brain to blood following first order kinetics at a fractional rate of 0.01123 ± 0.0030/min, a value virtually identical with a previously determined clearance rate of [<sup>125</sup>I]-IL-6. Area under blood concentration curve compared with that after intravenous injection shows that 31.6 ± 5.8% of the intracerebral dose reached peripheral blood in 4 h. Elevated ratios of superior sagittal sinus to aortic blood radioactivity concentration at 1 and 3 h (1.48 ± 0.26, p = 0.042; 1.95 ± 0.39, p = 0.026, respectively) indicate that TNF-α drains from brain at least in part via the sagittal sinus. Escherichia coli lipopolysaccharide i.c.v. injection increased the rate of brain efflux of TNF-α.

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          Most cited references 11

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          Cervical lymphatics, the blood-brain barrier and the immunoreactivity of the brain: a new view.

          This new view of the immunoreactivity of the normal brain is based on three key components. First, there is an active and highly-regulated communication between the brain and the central immune organs. Secondly, the connection from the brain to the draining nodes is much larger than previously appreciated. And third, the blood-brain barrier, by virtue of its selective permeability properties, contributes to the regulation of immunoregulatory cells and molecules in the brain cell microenvironment.
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            Distribution of extracellular tracers in perivascular spaces of the rat brain.

            Large molecular weight tracers (india ink or albumin labeled with colloidal gold, Evans blue or rhodamine) were micro-injected into the perivascular space of an artery or vein on the brain surface, or within the cerebral cortex or the subarachnoid space of anesthetized rats. The subsequent distribution was followed both under intravital microscopy, in order to outline the pathways and direction of tracer movement, and in histological section, in order to describe the pathways of flow at the light and electron microscopic level. The tracers remained largely in the perivascular spaces and in the interconnecting network of extracellular channels, including the subpial space and the core of subarachnoid trabeculae. Tracer also leaked across the pia into subarachnoid CSF. Bulk flow of fluid within the perivascular space, around both arteries and veins, was suggested from video-densitometric measurements of fluorescently labeled albumin. However, this flow was slow, and its direction varied in an unpredictable way. These results confirm that perivascular spaces may serve as channels for fluid exchange between brain and CSF, but do not support the idea that CSF circulates rapidly through brain tissue via perivascular spaces.
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              Induction of tumor necrosis factor-alpha mRNA in the brain after peripheral endotoxin treatment: comparison with interleukin-1 family and interleukin-6.

               S Gatti,  T Bartfai (1993)
              The constitutive expression of tumor necrosis factor-alpha (TNF alpha) mRNA and its induction (60 min later) by peripheral injection of Escherichia coli lipopolysaccharide (2 mg/kg i.p.) was demonstrated by polymerase chain reaction (PCR), in the pituitary and hypothalamus but not in the striatum or hippocampus of the rat. The pattern of TNF alpha mRNA induction is different from that observed for mRNAs of IL-1 alpha and IL-1 beta, IL-1ra and IL-6 respectively. This demonstration of the induction of TNF alpha in the brain may contribute to our understanding of the central effects of TNF alpha in fever and anorexia.
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                Author and article information

                Journal
                NIM
                Neuroimmunomodulation
                10.1159/issn.1021-7401
                Neuroimmunomodulation
                S. Karger AG
                1021-7401
                1423-0216
                1998
                October 1998
                14 September 1998
                : 5
                : 5
                : 261-269
                Affiliations
                Department of Medicine, College of Medicine, University of Arizona, The University of Arizona Health Sciences Center, Tucson, Ariz., USA
                Article
                26346 Neuroimmunomodulation 1998;5:261–269
                10.1159/000026346
                9730694
                © 1998 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 3, Tables: 3, References: 59, Pages: 9
                Categories
                Original Paper

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