Axo-glial pathology in Multiple Sclerosis and its potential effects on neurotransmission
Richard Reynolds (Medicine)
Aldo Faisal (Bioengineering/Computing)
Kambiz Alavian (Medicine)
Neuroinflammation is a feature of all neurodegenerative disorders of the human brain. In Multiple Sclerosis (MS) diffuse inflammation leads to pathological changes at the nodes of Ranvier, the regions of the nerve fibres where the electrical signals are amplified. This pathology contributes to nerve fibre/axonal degeneration, which is characteristic of the progressive stages of MS and may be responsible for some clinical symptoms frequently observed in MS patients, such as fatigue and cognitive deficit.
The interdisciplinary approach of this project carefully integrates histological analysis, computational models, ex-vivo culture models, in-vivo animal models and electrophysiology.
The main objective is determining the extent of the axonal pathology at the nodes of Ranvier through histological and immunofluorescence studies on human brain tissue provided by the UK Multiple Sclerosis Tissue Bank as well as from an animal model of inflammation. Using this molecular information, the second objective is to implement these changes into a computational model to simulate the conduction in an axon affected by neuroinflammation. The third objective is to generate an ex-vivo rat slice culture model of neuroinflammation to find a mechanism behind the observed pathology and use electrophysiological methods to test the hypotheses acquired with the computational model. Lastly, using the computational model we will determine whether modulation of specific ion channels using pharmacological tools could reverse the conduction deficits.