Speaker: Professor Richard Reynolds, Deputy Head, Brain Sciences, Imperial College Faculty of Medicine, London, England, Visiting Professor, Lee Kong Chian Medicine, Nanyang Technological University, Singapore

Neuroinflammation is suggested to play a pivotal role in many neurodegenerative conditions and it is suggested that chronic activation of microglia could be responsible for neurotoxicity. However, there is little definitive evidence in vivo for this deleterious role of microglia. Our studies in multiple sclerosis have shown that elevated levels of proinflammatory molecules in the CSF of the subarachnoid space overlying the cerebral cortical grey matter are associated with demyelination, microglial activation and neuronal loss. Protein and gene profiling have suggested that TNF and interferon-gamma may play a major role in this pathology. We have now modelled this scenario in the rat cortex using lentiviral delivery of proinflammatory cytokine genes into the meninges. Elevated levels of cytokines in the CSF in this model leads to chronic activation of microglia, but neurodegeneration is very dependent on the nature of the initial stimulus that activates the microglia. This talk with summarise the human tissue studies and the development of this new animal model of chronic microglial activation and neurodegeneration.