|
the Bank Statement
News from
The UK Multiple
Sclerosis Tissue Bank
.
(The Bank Statement is also available as a PDF document.)
Fibrin clots – good
guys and bad guys?
Dr Djordje Gveric
Institute of Neurology, University College
London
Fibrinogen is a protein that circulates in the blood and that can be thought
of as a member of a “rapid response team”. When a blood
vessel wall is torn at a site of injury anywhere in the body, fibrinogen
escapes from the blood and enters the surrounding tissue. Here single
molecules of fibrinogen stick to one another and form a mesh called
fibrin. Fibrin seals the tear and stops any further leakage from the
blood vessel. It also attracts cells and molecules to the site where
they play a role in the healing process. An essential step at the end
of this procedure is the removal of the fibrin; this is achieved by an enzyme
called tissue plasminogen activator (tPA) that dissolves away the fibrin mesh.
In multiple sclerosis lesions, fibrinogen escapes from the blood into brain
tissue across a broken down blood-brain barrier. Dr Gveric
has been looking to see whether the failure of successful repair
(remyelination) of MS lesions could be due fibrin not being cleared away from
the site. One of the ways in which the body controls the activity of tPA is with an enzyme inhibitor called plasminogen activator inhibitor-1 (PAI-1) which binds to tPA and inactivates it. When the group examined
active MS lesions they found an increase in the activity of PAI-1, a
resulting decrease in the activity of tPA, and an
accumulation of fibrin around blood vessels and on axons.
In this photograph, fibrin
is stained green and axons red - there is one running across
the photograph. The arrowheads point to areas where fibrin has
been laid down on the axon resulting in a yellow colour. The extended
presence of fibrin would inhibit the repair process and may actually favour
damage to axons by components of the immune system. Since the action of
tPA is inhibited by PAI-1, hindering the action of
PAI-1 would release tPA to dissolve the
fibrin. Dr Gveric’s group is now trying
to develop a strategy that will block the action of PAI-1 and so aid recovery
and reduce further damage.
Could preventing scarring
help repair?
Dr Nick Gutowski
Peninsula Medical School, Exeter
A part of the normal response of the body to damage is to form a scar; the
characteristic grey, firm MS lesion in the white matter is actually a scar
that has grown as the myelin and/or axons have been destroyed. These
scars mainly consist of a meshwork of fibres that are the outgrowth of a cell
resident in the normal CNS – the astrocyte.
Could this normal response of astrocyte scarring
actually be hampering remyelination?
Dr Gutowski’s group has been trying to find
out what makes a normal resting astrocyte turn into
cell that lays down a fibrous scar. The group first made
“identikits” that would allow astrocytes
at different stages along this process to be distinguished according to the
proteins that were present on the surface of each cell. Using the
identikits, the group were able to distinguish “scar” astrocytes that were present in MS lesions from resting astrocytes that were in MS brain tissue that did not
contain a lesion and in tissue from people that did not have MS.
The panel on the left shows
the edge of an MS lesion; scarring astrocytes in
the lesion have been marked with the identikit (black dots in right half of
picture).
Finding an accurate way to recognise scar astrocytes
was essential to be able to answer the next question: “what signals
make a resting astrocyte change into a scarring astrocyte?” Astrocytes
were isolated from tissue donated by people that did not have MS, and grown
in plastic dishes as shown in the photograph in the right panel above.
These resting astrocytes can then be used to test
the ability of chemical messengers to convert them into a scarring astrocyte as recognised by the identikit. It is
hoped that this work will lead to developing ways of stopping scarring; and
this combined with therapies that encourage remyelination may provide a means
of allowing demyelinated axons to regain their
function.
Emergency
Donor Line Number: 07659 132 045
In January 2005, we had to change the number of our 24-hour Emergency Donor
Line. This is the number that people should use if they need an
immediate response from the Tissue Bank; for example, to inform us of the
death of someone registered on our donor scheme. In the New Year we
sent all registered donors a new Donor Card, like this…
…if you are a
registered donor and do not have a card like this, please let us know.
Please also update the number on all your paperwork and let all relevant
people know of the change. We are very sorry for the inconvenience that
this is going to cause.
Please
let us know…if you
do not wish to receive another newsletter
Please
let us know…of any
changes that we need to make to our copy of your consent forms, (e.g. change
of address, next-of-kin or general practitioner)
Telephone:
020 7594 9734
Email:
ukmstissuebank@imperial.ac.uk
Post:
The UK Multiple Sclerosis Tissue Bank
Division of Neuroscience and Mental Health
Imperial College London
Hammersmith Campus
Du Cane Road
London W12 0NN
the Bank
Statement was written by
Abhi Vora
(Manager of the Tissue Bank)
page 5
page
1/ page
2/ page
3/ page 4/ page
5
|
