Fluid Environment of the Brain

283 Pages·1975·5.933 MB·English

by  Helen Cserr (Eds.)

ACADEMIC PRESS RAPID MANUSCRIPT REPRODUCTION
Proceedings of a symposium held at the
Mount Desert Island Biological Laboratory,
Salsbury Cove, Maine, September 11-13, 1974
Fluid Environment
of the Brain
EDITED BY
Helen F. Cserr
Brown University
Joseph D. Fenstermacher
National Cancer Institute
Vladimir Fend
Harvard Medical School
ACADEMIC PRESS, INC. New York San Francisco London 1975
A Subsidiary of Harcourt Brace Jovanovich, Publishers
COPYRIGHT © 1975, BY ACADEMIC PRESS, INC.
ALL RIGHTS RESERVED.
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ACADEMIC PRESS, INC.
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United Kingdom Edition published by
ACADEMIC PRESS, INC. (LONDON) LTD.
24/28 Oval Road, London NW1
Library of Congress Cataloging in Publication Data
Main entry under title:
Fluid environment of the brain.
Sponsored jointly by the Mount Desert Island
Biological Laboratory and the National Cancer In­
stitute.
Bibliography: p.
Includes index.
1. Brain-Congresses. 2. Cerebrospinal fluid-
Congresses. 3. Choroid plexus-Congresses.
I. Cserr, Helen F. II. Fenstermacher, Joseph D.
III. Fencl, Vladimir. IV. Mount Desert Island
Biological Laboratory, Salisbury Cove, Me. V. U-
nited States. National Cancer Institute. [DNLM:
1. Blood-Brain barrier—Congresses. 2. Cerebro­
spinal fluid-Congresses. WL203 F646 1974]
QP376.F58 612'.824 75-17919
ISBN 0-12-197450-2
PRINTED IN THE UNITED STATES OF AMERICA
Participants
Asterisks denote contributors to this volume.
Archie W. Bleyer, Division of Hematology/Oncology, Children's Orthopedic
Hospital and Medical Center, Seattle, Washington 98105
*Michael W.B. Bradbury, Department of Physiology, University of London
King's College, Strand, London WC2R 2LS, England
*Milton W. Brightman, Laboratory of Neuropathology and Neuroanatomical
Sciences, National Institute of Neurological Diseases and Stroke, Bethesda,
Maryland 20014
*Christian Crone, Institute of Medical Physiology A, University of Copenhagen,
2100 Copenhagen φ, Denmark
*Helen F. Cserr, Division of Biological and Medical Sciences, Brown University,
Providence, Rhode Island 02912
Donald Davis, Children's Hospital National Medica lCenter, Washington, D.C.
20009
Hugh Davson, Department of Physiology, University College London, London,
WC1E6BT, England
*Vladimir Fencl, Department of Anaesthesia, Peter Bent Brigham Hospital
and Harvard Medical School, Boston, Massachusetts 02115
*Joseph D. Fenstermacher, Membrane Transport Section, Division of Cancer
Treatment, National Cancer Institute, Bethesda, Maryland 20014
Mary K. Hammock, Department of Neurosurgery, Children's Hospital
National Medical Center, Washington, D.C. 20009
*Karl M. Knigge, Deparrment of Anatomy, University of Rochester School of
Medicine and Dentistry, Rochester, New York 14642
Irwin J. Kopin, Laboratory of Clinical Science, National Institute of Mental
Health, Bethesda, Maryland 20014
*Greg Koski, Department of Physiology, Harvard Medical School, Boston,
Massachusetts 02115
Abel Lajtha, New York State Research Institute of Neurochemistry and Drug
Addiction, Ward's Island, New York 10035
vii
PARTICIPANTS
Victor A. Levin, Naffziger Laboratories for Neurosurgical Research,
Department of Neurological Surgery, University of California, San
Francisco, San Francisco, California 94122
*Antonio V. Lorenzo, Neuropharmacology Section, The Children's Hospital
Medical Center and Harvard Medical School, Boston, Massachusetts 02115
Thomas H. Maren, Department of Pharmacology and Therapeutics, College of
Medicine, University of Florida, Gainesville, Florida 32610
*Marion Murray, Department of Anatomy, Medical College of Pennsylvania,
Philadelphia, Pennsylvania 19096
William H. Oldendorf, Veterans Administration, Wadsworth Hospital Center,
Los Angeles, California 90073
*John R. Pappenheimer, Department of Physiology, Harvard Medical School,
Boston, Massachusetts 02115
*Hanna M. Pappius, The Donner Laboratory of Experimental Neurochemistry,
Montreal Neurological Hospital and McGill University, Montreal, Quebec
H3A 2B4, Canada
Robert Parks, Jr., Division of Biological and Medical Sciences, Brown
University, Providence, Rhode Island 02912
*Clifford S. Patlak, Theoretical Statistics and Mathematics Branch, Biometry
Division, National Institute of Mental Health, Bethesda, Maryland 20014
Fred Plum, Department of Neurology, Cornell University Medical College,
New York, New York 10021
Michael Pollay, Division of Neurosurgery, School of Medicine, The University
of New Mexico, Albuquerque, New Mexico 87131
David P. Rail, National Institute for Environmental Health Science, Research
Triangle Park, North Carolina 27709
*Stanley I. Rapoport, Laboratory of Neurophysiology, National Institute of
Mental Health, Bethesda, Maryland 20014
Donal J. Reed, Department of Pharmacology, University of Utah College of
Medicine, Salt Lake City, Utah 84112
William R. Shapiro, Neuropsychiatrie Service, Memorial Sloan-Kettering
Cancer Center, New York, New York 10021
Louis Sokoloff, Laboratory of Cerebral Metabolism, National Institute of
Mental Health, Bethesda, Maryland 20014
S^ren C. S^rensen, Institute of Medical Physiology A, University of
Copenhagen, 2100 Copenhagen 0, Denmark
Donald B. Tower, National Institute of Neurological Disease sand Stroke,
Bethesda, Maryland 20014
*John E. Treherne, A.R.C. Unit of Invertebrate Chemistry and Physiology,
Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ,
England
viii
PARTICIPANTS
Anthonie Van Harreveld, Division of Biology, California Institute of
Technology, Pasadena, California 91109
Betty P. Vogh, Department of Pharmocology and Therapeutics, College
of Medicine, University of Florida, Gainesville, Florida 32610
*Marthe Vogt, Agricultural Research Council Institute of Animal Physiology,
Babraham, Cambridge, CB2 4AT, England
*Keasley Welch, Neurosurgery, The Children's Hospital Medical Center and
Harvard Medical School, Boston, Massachusetts 02115
* Jacques Weyne, Laboratorium voor Normale en Pathologische Fysiologie,
Rijksuniversiteit, De Pintelaan 135, Gent, Belgium
Leslie I. Wolfson, Department of Neurology, Albert Einstein College of
Medicine, Bronx, New York 10461
Dixon M. Woodbury, Department of Pharmacology, University of Utah
College of Medicine, Salt Lake City, Utah 84132
*Ernest M. Wright, Department of Physiology, University of California
School of Medicine, Los Angeles, California 90024
C. Gordon Zubrod, Comprehensive Cancer Research Center of Greater
Miami, University of Miami, Miami, Florida 33136
ix
Preface
The immediate fluid environment of neurons and neuroglia is a thin film of
interstitial fluid, on the order of 150 to 20ο0 A i tnhickness, which communi­
cates via patent extracellular fluid channels with the cerebrospina flluid (CSF)
of the ventricular and subarachnoi dspaces. In view of the crucial role of the
central nervous system to th eorganism, plus the exquisite sensitivity of neu­
ronal function to the concentration sof various organic and inorganic constitu­
ents of extracellular fluid, it is not surprising to discover that t fhleuid environ­
ment of the brain—cerebral interstitia flluid and CSF-enjoys a far greater
degree of homeostasis, regulation, and freedom generally from the vicissitudes
of the external environment than do peripheral interstitial fluids.
Our aim in studying th feluid matrix of the brain i sultimately to understand
the functional relationships among neurons, neuroglia, and their extracellular
fluids in normal and pathologica lstates. Although we have come a long way
toward achieving this aim since the time o Gfalen, who believed that animal
spirits reside in the ventricula cravities, or even since the 1950s, when early
electron microscopists claimed ther eis little o rno cerebral interstitial fluid, we
still have only a rudimentary knowledge of even the mos btasic characteristics
of the fluid environment of the brain.
Cerebral interstitial fluid, CSF, and the membranes-or barrier mechanisms-
which contribute to the regulation o tfhe physical and chemical characteristics
of these fluids are subjects of interest to most researchers in the neurological
sciences, not only from theoretical but also from practical points of view.
Specifically, the very effectiveness of brain-barrier systems frequently presents
experimental problems which, for their solution, require a detailed knowledge
of the characteristics of blood-brain exchange T.hus, for the pharmacologist
and clinician, the blood-brain and blood-CSF barriers provide hindrance to the
effective delivery of drugs to nervous tissue; for the physiologist, they compli­
cate the study of the variou fsluid compartments of the brain; and, for the
neurochemist, they interfere with the easy deliver oyf precursors, metabolites,
and inhibitors.
Prior to the publicatio nof Professor Hugh Davson's monograph, The Physi­
ology of the Ocular and Cerebrospinal Fluids, in 1956, the fluids of the central
xi
PREFACE
nervous system were generally considered the domain o cflinical researchers
interested in pathological conditions such as cerebral edema and hydro­
cephalus. Since the appearance of this monograph, a steadily increasing number
of basic scientists hav ebecome attracted to the area, and several symposia have
been held (including Amsterdam, 1966; Williamsburg, 1968; Oxford, 1970; and
Copenhagen, 1970). This book presents the proceedings o fthe most recent of
these meetings, held in Bar Harbor, Maine in September of 1974 under the
joint sponsorship of the Mount Desert Island Biological Laboratory and the
National Cancer Institute. Most of the participants shared a common interest in
the fluxes of material between the various extracellular fluid compartments of
the brain. Accordingly, the program was organized along these lines. Following
an introductory chapter outlining anatomical relationships, the book deals con­
secutively with the physiology of the blood-brai bnarrier, physiology of the
choroid plexus, and exchange between cerebrospinal fluid an dbrain. In the
final section, special consideration is given to recent attempts to use CS Fas a
means of studying the chemistry, metabolism, and possible endocrine functions
of the brain.
We wish to express our gratitude to the many individuals from the Mount
Desert Island Biological Laboratory who assisted with the symposium; to the
National Cancer Institute (NCI) for generous financial support; to both Dr. C.
Gordon Zubrod, former director of the Division of Cancer Treatment, NCI,
and Dr. Vincent T. Oliverio, Associate Director for Experimental Therapeutics,
NCI, who facilitated the funding of the meeting; and, to Mrs. Barbara Musiker
who has so patiently typed the manuscript.
xii
MORPHOLOGY OF THE WALLS AROUND
FLUID COMPARTMENTS IN NERVOUS TISSUE
M.W. Brightman, R.R. Shivers* and L. Prescott
J. Introduction
II. Methods
III. Observations
A. Junctions
B. Extracellular Clefts
C. Transverse Channels
IV. Discussion
I. Introduction
The composition of the fluid immediately bath­
ing neuronal, glial and endothelial cells of the
central nervous system is determined, in part, by
intercellular junctions. One type of junction in
particular, the tight junction, is the effective one
in establishing a sharp concentration gradient of
large molecules between fluid compartments. The
tight junctions, organized as a series of belts be­
tween endothelial cells, effectively isolate peri­
cellular fluid channels from blood (Reese and
Karnovsky, 1967) with respect to the protein, horse­
radish peroxidase (HRP) (MW 40,000) and the much
smaller heme-peptide, microperoxidase, (MW 1800)
(Feder et al., 1969). Zonules of tight junctions
between the epithelial cells of the choroid plexus
also block this protein and peptide from entering
Laboratory of Neuropathology and Neuroanatomical
Sciences, National Institute of Neurological Diseases
and Stroke, National Institutes of Health, Bethesda,
Maryland, U.S.A.
*The present address of R.R. Shivers is Department
of Zoology, University of Western Ontario, London 72,
Ontario, Canada.
3
M. W. BRIGHTMAN et al.
the ventricular cerebrospinal fluid in appreciable
amount (Becker et al., 1967; Brightman, 1968). A
third site where the same kind of junctions influence
exchange of protein or heme-peptide is the special­
ized ependyma or tanycytes of the median eminence in
the floor of the third ventricle. Here, too, tight
junctions unite adjacent ependymal cells in this part
of the hypothalamus (Reese and Brightman, 1968). A
fourth cell layer where tight junctions have an ef­
fect is actually over the surface of the brain and
spinal cord. Between two particular layers of the
arachnoid membrane, the "barrier cell layer," rows
of tight junctions block the passage of HRP to and
from the subarachnoid space (Nabeshima et al., 1975).
However, the same tight junctions that block
the movement of protein and peptide may allow smaller
molecules to pass. In choroidal epithelium, for ex­
ample, some tight junctions are penetrated by lan­
thanum hydroxide, a molecule that is smaller than
the peroxidases used (Brightman and Reese, 1969).
Another unexpected observation was that a few of
the attachments classified as tight junctions be­
tween some cells of the arachnoid membrane
(Nabeshima et al., 1975) and endothelium of the durai
venous sinus (Shabo and Brightman, 1972) have a nar­
row but patent cleft.
This presentation compares the tight junctions
of meninges, choroidal epithelium and special epen­
dyma in thin plastic sections and in replicas of
freeze-fractured tissue examined electron microscop­
ically. In such replicas, broad planes within cell
membranes are exposed and some impressions thereby
gained as to the probable openness of junctions.
Comparisons are also made on how the arrangement of
glial cells may affect the progress of solute in the
extracellular fluid of vertebrates and the ventral
nerve cord of one invertebrate, the crayfish.
II. Methods
In mammals, the central nervous system was
fixed by a solution of formaldehyde and glutaralde-
hyde that was perfused through the aorta (Reese and
Karnovsky, 1967). In the crayfish, best preserva­
tion was obtained by direct immersion of the
4