Repair and Regeneration of the Nervous System: Report of the Dahlem Workshop on Repair and Regeneration of the Nervous Sytem Berlin 1981, November 29 – December 4

402 Pages·1982·8.44 MB·English

by  J. G. Nicholls (auth.)

Dahlem Workshop Reports
Life Sciences Research Report 24
Repair and Regeneration of the Nervous System
The goal of this Dahlem Workshop is:
to define how the nervous system is able
to restore function after injury
by repairing connections or
by compensatory mechanisms
Life Sciences Research Reports
Editor: Silke Bernhard
Held and published on behalf of the
Stifterverband fUr die Deutsche Wissenschaft
Sponsored by:
Heinz Breuninger Stiftung GmbH
Hermann und Lilly Schilling-Stiftung
fUr Medizinische Forschung
im Stifterverband fUr die Deutsche Wissenschaft
Repair and Regeneration
of the Nervous System
J. G. Nicholls, Editor
Report of the Dahlem Workshop on
Repair and Regeneration of the Nervous System
Berlin 1981, November 29 - December 4
Rapporteurs:
H. J. Anderson' J. W. Lichtman' M. E. Raichle . C. J. Shatz
Program Advisory Committee:
J. G. Nicholls, Chairman' W. M. Cowan' W. E. Crill
H.-J. Freund' N. N. Herschkowitz . J. K. S. Jansen' D. Purves
W.J.Singer
Springer-Verlag Berlin Heidelberg New York 1982
Copy Editors: M. Cervantes-Waldmann, K. McWhirter
Photographs: E. P. Thonke
With 4 photographs, 30 figures, and 3 tables
ISBN -13: 987-3-642-68634-4 e-ISBN -13: 987-3-642-68632-0
001: 10.1007/987-3-642-68632-0
CIP-Kurztitelaufnahme der Deutschen Bibliothek:
Repair and regeneration of the nervous system: report of the Dahlem Workshop
on Repair and Regeneration of the Nervous System, Berlin 1981, November 29 -
December 41 J. G. Nicholls, ed. Rapporteurs: H. J. Anderson ...
[Dahlem Konferenzen. Held and publ. on behalf of the Stifterverb. for d. Dt. Wiss.
Sponsored by: Heinz-Breuninger-Stiftung GmbH; Hermann-u.-Lilly-Schilling
Stiftung fUr Med. Forschung im Stifterverb. fUr d. Dt. Wiss.]. - Berlin; Heidelberg;
New York: Springer, 1982
(Life sciences research report; 24)
(Dahlem Workshop reports)
NE: Nicholls, John G. [Hrsg.]; Anderson, Hilary, J. [Mitverf.J; Workshop on Repair
and Regeneration of the Nervous System <1981, Berlin, West>;
Dahlem Konferenzen; 1. GT
This work is subject to copyright. All rights are reserved, whether the whole or
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to "Verwertungsgesellschaft Wort", MUnchen.
© Dr. S. Bernhard, Dahlem Konferenzen, Berlin 1982.
Sottcover reprint of the hardcover 1st edition 1982
The use of registered names, trademarks, etc. in this publication does not imply,
even in the absence of a specific statement, that such names are exempt from
the relevant protective laws and regulations and therefore free for general use.
2131/3014 - 5 4 3 2 1 0
Table of Contents
The Dahlem Konferenzen .................................... vii
Introduction
J.G. Nicholls ............................................ .
A Synoptic View of the Development of the Vertebrate
Central Nervous System
W.M. Cowan................................................ 7
Normal and Abnormal Development of the Human Nervous
System
N.N. Herschkowitz and G.M. McKhann ........................ 25
Factors That Influence Neural Development in Nematodes
H.R. Horvitz.............................................. 41
Acute Neural Reaction to Injury
G. W. Kreutzberg........................................... 57
Molecular Events in Axonal Regeneration
M. Willard and J.H.P. Skene............................... 71
Transplantation of Neurons and Sheath Cells - A Tool for
the Study of Regeneration
A.J. Aguayo, P.M. Richardson, S. David, and M. Benfey ..... 91
Guidance ofAxons During Development and After Nerve
Injury
D. Purves .........................•....................... 107
Regeneration of Synapses
J.R. Sanes ...................................•............ 127
Cell Recognition and Specific Synapse Formation
K.J. Muller ............................................... 155
Factors Involved in the Regulation of the Survival and
Differentiation of Neurons
H. Thoenen, Y.-A. Barde, and D. Edgar ..................... 173
Regeneration and Repair of the Nervous System: Clinical
Aspects
H.-J. Freund and H.J. Bauer ............................... 187
vi Table of Contents
Recovery Mechanisms in the Mammalian Brain
W. Singer................................................. 203
Clinical Evaluation of Injury and Recovery
W.E. Crill and M.E. Raichle ............................... 227
Adaptive and Maladaptive Regeneration in the Spinal Cord
E. Frank .................................................. 243
Temporal Changes After Spinal Cord Injury
L. Mendell ................................................ 255
Electroneuroprostheses: Usefulness in Rehabilitation
B.S. Nashold, Jr .......................................... 269
Neural Development: Implications for Recovery from Injury
Group Report
C.J. Shatz, Rapporteur
M. Bate, F.J. Bonhoeffer, W.M. Cowan, S.S. Easter
N.N. Herschkowitz, H.R. Horvitz, G.M. McKhann,
F. Rathjen, M. Schachner, T.A. Sears ...................... 289
Early Responses to Neural Injury
Group Report
H.J. Anderson, Rapporteur
A.J. Aguayo, S.E. Blackshaw, D. Bray, R.W. Gilliatt,
A.D. Grinnell, G.W. Kreutzberg, I. Parnas, D. Purves,
S. Rotshenker, M.E. Schwab, M.B. Willard .................. 315
Factors Involved in the Restoration of Specific Neural
Connections
Group Report
J.W. Lichtman, Rapporteur
T.P. Feng, J.K.S. Jansen, B. Katz, J.B. Martin, K.J. Muller,
J.G. Nicholls, G. Raisman, J.R. Sanes, J. Schnitzer,
E.M. Shooter, H. Thoenen, N. Tsukahara, T.N. Wiesel ....... 343
Restoration of Function
Group Report
M.E. Raichle, Rapporteur
D.Y. von Cramon, W.E. Crill, H. Flohr, E. Frank,
H.-J. Freund, K.-A. Hossmann, L.M. Mendell, M. Mishkin,
B.S. Nashold, Jr., W. Precht, J. Zihl .•................... 383
List of Participants ..............................•....... 399
Subject Index ............................................• 405
Author Index ...................................•..••...... 411
The Dahlem Konferenzen
DIRECTOR:
---------
Silke Bernhard, M.D.
F-O-U--N-D-A-T-IO--N-:
Dahlem Konferenzen was founded in 1974 and is supported by the
Stifterverband fUr die Deutsche Wissenschaft*, in cooperation
with the Deutsche Forschungsgemeinschaft** and the Senat of
the City of Berlin.
OBJECTIVES:
-----------
The task of Dahlem Konferenzen is:
to promote the interdisciplinary exchange of scientific in
formation and ideas,
- to stimulate international cooperation in research, and
- to develop and test different models conducive to more effec-
tive scientific meetings.
AIM:
Each Dahlem Workshop is designed to provide a survey of the
present state of the art of the topic at hand as seen by the
various disciplines concerned, to review new concepts and tech
niques, and to recommend directions for future research.
-T-O-P-IC--S-:
The workshop topics (in the Life Sciences and the field of
Physicoche~istry) should be:
- of contemporary international interest,
- timely,
interdisciplinary in nature, and
- problem-oriented.
PROCEDURE:
Dahlem Konferenzen approachEs internationally recognized scien
tists to suggest topics fulfilling these criteria and to pro
pose members for a Program Advisory Committee, which is re
sponsible for the workshop's scientific program. Once a year,
the topic suggestions are submitted to a scientific board for
approval.
*
ThE Donors Association for the Promotion of Sciences and
Humanities
**
German Science Foundation
viii The Dahlem Konferenzen
-PA--R-T-I-C-IP-A-N--T-S-:
The number of participants is limited to 48 for each workshop.
They are selected exclusively by a Program Advisory Committee.
Selection is based on international scientific reputation alone
and is independent of national considerations, although a bal
ance between Europeans and Americans is desirable. Exception
is made for younger German scientists for whom 10% of the places
are reserved.
THE DAHLEM WORKSHOP MODEL:
--------------------------
A special workshop model has been developed by Dahlem Konferenzen,
the Dahlem Wo~k~hop Model. The main work of the workshop is
done in four small, interdisciplinary discussion groups, each
with 12 members. Lectures are not given.
Some participants are asked to write background papers_providing
a review of the field rather than a report on individual work.
These are circulated to all participants 4 weeks before the
meeting with the request that the papers be read and questions
on them formulated be6o~e the workshop, thus providing the basis
for discussions.
During the workshop, each group prepares a report reflecting the
essential points of its discussions, including suggestions for
future research needs. These reports are distributed to all
participants at the end of the workshop and are discussed in
plenum.
PUBLICATION:
------------
The Dahlem Workshop Reports contain:
- the Chairperson's introduction,
- the Background Papers, and
- the Group Reports.
The Dahlem "']orkshop Reports are available in two series:
1) Life Sciences Research Reports (LS) and
2) Physical and Chemical Sciences Research Reports (PC).
DAHLEM KONFERENZEN, Wallotstrasse 19, D-1000 Berlin 33,
Federal Republic of Germany
Repair and Regeneration of the Nervous System, ed. J.G. Nicholls, pp. 1-5.
Dahlem Konferenzen 1982. Berl in, Heidelberg, New York: Springer-Verlag.
Introduction
J. G. Nicholls
Dept. of Neurobiology, Stanford University School of Medicine
Stanford, CA 94305, USA
This volume deals with a key problem in modern biology and clini
cal neurology, namely, the way in which the nervous system is
able to repair itself, to restore function, and to regenerate
synaptic connections. Faced with patients suffering from a
stroke, a severed peripheral nerve, or an injury to the spinal
cord, the clinician has to assess the extent of the lesion and
the possibility of recovery, and, if recovery does occur, the
mechanism by which it has been brought about. To what extent
can the restoration of function in a patient be attributed to
collateral sprouting, to some neurons taking over the function
of others, or to regeneration? At the same time, the mechanisms
involved in the responses to injury of neurons and glial cells,
in growth and in recovery, represent tantalizing problems for
the cell biologist and neurobiologist interested in the develop
ment and function of the nervous system. Accordingly, it seemed
particularly appropriate for there to be a Dahlem Workshop deal
ing with regeneration and restoration of function in the nervous
system, with its main focus being on the interactions not only
between basic scientists from widely different disciplines, but
also with clinicians who everyday see patients suffering from
damage to the nervous system that results from trauma or disease.
2 J.G. Nicholls
What is striking is how much the field has advanced over the
past few years, and how different this dialogue is now compared
to what was possible just a few years ago. In the past, there
was a great deal of information available about regeneration in
the peripheral nervous system, particularly with respect to the
re-innervation of skeletal muscles in frogs and mammals. How
ever, little was known about the biochemistry of acetylcholine
receptors, the role of activity in regulating supersensitivity,
or the properties of the basal lamina. Similarly, for the cen
tral nervous system, it was taken for granted that the mamma
lian brain had little or no power of regeneration following an
injury, apart from limited sprouting with no obvious functional
consequence. The only definite examples of central nervous sys
tem regeneration were obtained in invertebrates and lower ver
tebrates, and there the most intensively studied systems were
the connections from retina to tectum in frogs, fishes, and
salamanders. The phenomena revealed an extraordinary degree of
plasticity in the eNS. Thus, in a frog, if the optic nerve was
cut, fibers could be shown to grow back from the retina to the
tectum, where they became reconnected to their original targets
with sufficient accuracy for function to be restored, enabling
the frog to see once again. This type of experiment poses a
range of questions that still need to be considered today and
that serve as a focus for the organization of this volume.
1) What are the effects of sectioning axons on the cell body,
and how is sprouting induced? What are the mechanisms by which
a neuron is made to extend its processes?
2) Once neurons are growing, what determines the direction that
the axons will take, and what interactions occur between the
neurons and the glial cells or Schwann cells that surround them?
3) When neurons reach their destination, what signals pass from
the targets or from associated structures to terminate growth
and to induce the specialization of terminals?
4) What determines whether a cell will make connections with
another cell or will fail to do so? If errors are made, are
they corrected?