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Welcome
Introduction
How
to register as a tissue donor
Raising awareness of all those affected by MS
Donation
of Tissue
Requesting
tissue for research on multiple sclerosis
Promoting the Tissue Bank in the research community
The Bank
Statement
Articles
Links:
Department
of Cellular and Molecular Neuroscience
Department
of Neuropathology
Multiple Sclerosis Society of Great
Britain and Northern Ireland
International Federation of Multiple Sclerosis
Societies
E-mail: ukmstissuebank@imperial.ac.uk
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the Bank Statement
News from
The UK Multiple
Sclerosis Tissue Bank
.
(The Bank Statement is also available as a PDF document.)
A source of antibodies in
the brain of patients with MS
Dr Francesca Aloisi
Istituto Superiore di Sanita, Rome, Italy
Another usual suspect that should be looked at very carefully whenever the
immune system is involved in injury is the antibody. Circumstantial evidence
suggesting a role for antibodies in causing damage in MS comes from their
presence in the fluid that bathes the brain and spinal cord (cerebrospinal
fluid, CSF). It is these antibodies that are detected in the sample of CSF
drawn from a lumber puncture, and that help the diagnosis of MS. Dr Aloisi's
research is aimed at finding out how these antibodies are made within the
brains of MS patients.
Antibodies are produced by plasma cells; plasma cells develop from B cells. B
cells can be found in lymph nodes and in the blood.In the nodes, the B cells
are organised into small sacs called follicles that are extremely efficient
at producing antibodies. Dr Aloisi asked whether these antibody producing
factories were responsible for making antibodies in the brains of people with
MS.
The study, initiated in Rome
and continued in the Tissue Bank laboratories by Dr Roberta Magliozzi, used
special staining techniques to detect cells and molecules that are unique to
B cell follicles. Follicles, containing multiplying B cells, plasma cells,
and other cells and chemical messengers necessary for the production of
antibodies were found within the brains of patients that had had the
secondary progressive form of MS. All this evidence taken together suggests
that B cell follicles may indeed be responsible for the sustained production
of antibodies within the brains of MS patients. Follicles were not found in
tissue from patients that had had other forms of MS or in tissue from
patients that did not have MS.
In this picture of a B cell
follicle, the fluorescent blue dye marks the nuclei of all cells; but most of
these are plasma cells. The green stain is picking out the antibodies. The
mass of green stain shows that large amounts of antibody are being produced
by plasma cells in this follicle. The antibody is leaking into the
surrounding brain tissue.
When B cell follicles were present, they were only found in the membranes
(meninges) that encase the brain; they were never seen within demyelinated
lesions. However, single B- and plasma cells were present within some
lesions, which raises the question: what is the relationship between the
presence of antibody producing B cell follicles in the meninges and the
presence of B/plasma cells in lesions, and how is all that related to the
degree of demyelination? Dr Aloisi's group is now working to answer these
important questions because if these antibodies prove to have a role in the
destruction of myelin, then developing strategies that would inhibit the
formation B cell follicles may be beneficial to patients with secondary
progressive MS.
Nodes of Ranvier during
demyelination and remyelination
Dr Owain Howell
Dept. of Cellular & Molecular
Neuroscience, Imperial College London
If one looks carefully along the length of a myelinated axon, one finds that
the myelin is not present as one uniform coating, but that there are minute
gaps (called nodes of Ranvier) at which the axon is
“naked”. This structure, consisting of stretches of
insulation (myelinated axon) interrupted by un-insulated gaps (the nodes),
allows the “electrical” nerve impulses, to jump from one node to
the next in a process called saltatory conduction. The formation and
maintenance of the nodes is therefore vital to the ability of the axon to
rapidly conduct messages to and from the rest of the body and within the
brain itself.
Working in collaboration with Professor Brophy at the University of
Edinburgh, Dr Howell has been studying the edges of the node - the very point
at which myelination stops. Here, the myelin sheets bind tightly to the
axon using “sticky proteins” called adhesion molecules; Dr Howell
has been looking at the presence of one such molecule called neurofascin in
MS brain tissue in order to see how its presence changes during the transition
from normal tissue to demyelinated lesion and from demyelinated lesion to
remyelinated lesion. In the three pictures below,
very thin slices of tissue
were treated with a green fluorescent dye that stains neurofascin and a red
dye that picks-up myelin. The first picture shows the
“normal” situation. There are two axons lying next to each,
running across the picture with their envelope of myelin stained red.
The arrow heads show the position of two nodes. The nodes are flanked
on both sides by the green staining neurofascin. The middle panel shows
an area in which there is on-going demyelination. The neurofascin is no
longer present as a pair of discrete bands, but has now spread along the axon
- arrow. The last panel shows an area that is remyelinating; here the
neurofascin has again become concentrated into discrete bands. It is
thought that with time the middle band will be lost so that a “normal”
situation similar to the one shown in first panel is re-established.
The effective conduction of nerve impulses along an axon is dependent upon
the presence of nodes of Ranvier; this study shows what happens to these
vital structures during demyelination and remyelination. The study
again demonstrates the complexity of repair and highlights just one structure
that needs to be rectified in a large re-construction in order for normal
function to be restored after an injury.
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