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The University of Southampton
BRAIN UK

Lay Summaries of studies supported by BRAIN UK by category: Demyelination

BRAIN UK Ref: 11/001
Role of neutrophils in the pathogenesis of neuromyelitis optica
Mr M C Papadopoulos, St. George’s University of London 

Neuromyelitis optica (NMO, Devic’s disease) is an autoimmune inflammatory disorder of the central nervous system which results in the loss of the conducting sheath of nerve fibres located preferentially in the optic nerve and spinal cord resulting in weakness, paralysis and loss of sensation (including blindness). NMO is related to multiple sclerosis (MS) which tends to affect the brain preferentially. NMO is associated with circulating autoimmune antibodies which bind to a particular molecule (aquaporin-4, AQP4) present on the surface of astrocytes which are diagnostic of NMO. The researcher’s team has developed an animal model of NMO by introducing these autoimmune antibodies into mouse brain and have discovered that inflammatory tissue damage is mediated by a particular type of cell called a neutrophil that is a normal constituent of the immune system. A molecule called neutrophil elastase can be detected in tissue using specific staining procedures and is specific for neutrophils and this study aims to test the hypothesis that tissue damage in NMO (but not MS) is mediated by neutrophils in support of data from previous mouse studies.

Project Status: Closed

BRAIN UK Ref: 16/010
Selective vulnerability in MND/FTD
Dr O. Ansorge, University of Oxford 

Motor neuron disease (MND) is a progressive neurodegenerative disorder that destroys motor neurons, the cells that carry the signal for muscle movement such as speaking, walking, breathing, and swallowing. There are different types of motor neurons which can be grouped depending on whether they are carrying signals around the brain and spine (upper motor neurons) or from the spine to the muscles (lower motor neurons). They can be further grouped depending on whether they are signalling fast acting or quickly fatiguing movements. Certain groups of neurons are affected differently during the course of motor neuron disease. The most significant degeneration (decline) of neurons in MND occurs within the spinal cord, however there is also moderate loss of upper motor neurons in the brain and spine.

We are particularly interested in upper motor neuron vulnerability. To investigate this, we will look for proteins that characterise neuron subtypes in conjunction with proteins that charcterise the disease effects, to identify whether particular neurons are more likely to collect disease-related proteins.

Project Status: Closed

Research Outputs: Presentation, Poster

BRAIN UK Ref: 20/003
Cellular and genetic pathomechanisms of central pontine myelinolysis
Dr Konstantin Glebov, University of Plymouth 

Lay Summary not yet available.

Project Status: Active

 

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BRAIN UK Ref: 20/004
Ultrastructural Endoneurial Pathology to Explain the Normal Function of the Human Blood Nerve Barrier and the Pathogenesis of Inflammatory Nerve Disease.
Professor Alison Lloyd, University College London 

Peripheral nerves (PN) communicate information to the brain from surface tissues and back to muscles to make responses. Peripheral neuropathies are conditions in which those nerves can become damaged resulting in numbness, pain or weakness. PN are very small and understanding how the 6 known types of cells within the nerve communicate in health and disease has evaded study. We aim to study nerves in health and in relation to three diseases which are described below. 

CIDP- Chronic Inflammatory Demyelinating Neuropathy
This is a disease whereby the individuals immune system attacks the peripheral nerves (i.e. nerves in the arms and legs) leading to weakness and sensory loss. The immune system damage results in the myelin sheath of the nerve (the ‘insulating’ cover of the nerve which allows the nerve to fire nerve impulses) being damaged which is termed demyelination. This occurs over several weeks to months, and can continue indefinitely if not treated.  

POEMS – Polyneuropathy, organomegaly, endocrinopathy, monoclonal disorder and skin disease.
This is a very rare cause of nerve damage and is the result of an abnormal blood cancer cell leaking inflammation molecules which cause damage to peripheral nerves. This results in the 5 key symptoms of POEMS syndrome- the Polyneuropathy (multiple nerves in the arms and legs damaged), Organomegaly (enlarged organs), Endocrinopathy (hormaon problems), Monoclonal disorder (the blood cancer) and Skin lesions. We believe the inflammation molecules in POEMS syndrome leads to damage and leak at the blood nerve barrier but this has never been studied before. 

Multiple myeloma
Is a similar blood condition to POEMS syndrome but doesn’t cause neuropathy per se and is therefore of interest to compare. 

Professor Lloyd’s team are the first to identify, classify and image the 6 nerve supporting cell types. They have demonstrated through visualisation under highly powered microscopes in mouse and rat nerves how the cells of the blood vessels interact with specialised nerve supporting cells to keep the blood nerve barrier impermeable. They have also discovered how special types of white blood cells important in immune function called macrophages remove potentially damaging substances which enter the nerve through the barrier.

We wish to look at the nerve supporting cell types in specimens from human specimens without disease, and in CIDP, POEMS and myeloma patients. These nerve samples will have already taken and used for clinical diagnostic use. We will use these nerve samples to see if the same appearances of nerve supporting cells, macrophages and blood vessels are present in human nerve and if they are altered in POEMS and CIDP.

Abbreviations
POEMS: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder, Skin lesions
CIDP: Chronic Inflammatory Demyelinating Polyneuropathy

Project Status: Active

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