NeuroResource Tissue Bank

Dr Jia Newcombe

The NeuroResource Tissue Bank provides material for research on CNS diseases in which the immune system is involved in the pathogenesis, and also for studies on the normal brain and spinal cord.

The Tissue Bank accepts donations of CNS tissues from patients who have MS, motor neurone disease, stroke, brain tumours, migraine or chronic pain, and from people without a neurological disease. We are able to help researchers in the U.K. and abroad to carry out studies on the cause and treatment of these disorders. Samples are used for a wide spectrum of research projects employing techniques such as single cell PCR, tissue microarrays and proteomic-based analyses. The Tissue Bank comes within the governance of the Queen Square Brain Bank (Professor Tamas Revesz).

Myeloperoxidase is a myeloid-specific haem enzyme which can generate a number of reactive species that induce apoptosis and tissue damage in pathways leading to chlorotyrosine and nitrotyrosine generation. In our studies on the role of myeloperoxidase in he immunopathogenesis of MS lesions, myeloperoxidase was detected in monocytes infiltrating active MS plaques, and 3 - chlorotyrosine was seen in two morphologically distinct populations of oligodendrocytes. Hypochlorite - mediated modified proteins were localised in a reactive astrocyte sub-population. We are currently examining the role of myeloperoxidase-generated toxic products in the propagation of inflammatory demyelination.

We have also investigated the expression of CD59 (protectin) epitopes in active and chronic MS lesions. CD59, a gly cophosphatidylinositol (GPI) anchored membrane protein, is an inhibitor of complement-induced lysis. In normal CNS white matter the monoclonal antibody A35, directed against a CD59 epitope, immunostained only blood vessel walls. However, strong staining was seen throughout very early MS plaques in which myelin loss was not yet detectable. A macrophage subpopulation was A35-immunopositive in demyelinating lesions, and individual myelinated axons were visualized at the borders of older plaques. Enzyme treatment to release GPI-anchored molecules abolished staining with anti- CD59 antibodies. Further studies are being carried out on the role of the A35-immunopositive CD59 epitope which appears to be localized on myelin damaged at a very early stage in the demyelinating process.

Other recent and ongoing research in our laboratory includes studies on the role of macrophages in oligodendrocyte damage, the expression of cannabinoid receptors in demyelinating disease, the detection of factors inhibiting remyelination, aberrant expression of sodium channels and annexins on axons and glial cells in MS lesions, detection of B lymphocyte-related chemokines and their receptors in the CNS of MS patients, and characterization of choline transporters in the normal human CNS and in neurological diseases.

Page last modified on 22 sep 09 18:25