Sergiu Groppa - Translational Methods for Multiple Sclerosis Research

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Neuromethods publishes cutting-edge methods and protocols in all areas of neuroscience as well as translational neurological and mental research. Each volume in the series offers tested laboratory protocols, step-by-step methods for reproducible lab experiments and addresses methodological controversies and pitfalls in order to aid neuroscientists in experimentation. Neuromethods focuses on traditional and emerging topics with wide-ranging implications to brain function, such as electrophysiology, neuroimaging, behavioral analysis, genomics, neurodegeneration, translational research and clinical trials. Neuromethods provides investigators and trainees with highly useful compendiums of key strategies and approaches for successful research in animal and human brain function including translational bench to bedside approaches to mental and neurological diseases.

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The underlying pathology of MS is characterized by focal lesions and ongoing white and gray matter compartment pathology. Importantly, functional and structural reorganization occurs continuously during the disease course and plays an essential role for the long-term outcome. These cannot be precisely quantified in humans. Particularly at different disease stages processes of demyelination, remyelination, and axonal remodeling occur simultaneously and influence the disease course. An exact understanding of these distinct disease-related fingerprints could be achieved through the use of translational models (forward and reverse translation) of neuroinflammation. Unraveling complementary paths of tissue damage and restoration in humans and rodents could give important answers to inter-individual disease courses and build up an essential background for the improvement of actual therapeutic strategies and facilitate the development of future remedies. On the basis of recent results on the importance of MRI-derived characterization of tissue integrity and cerebral network fingerprints for neuroinflammation, we summed up current advances in the study of translational paths in central neuroinflammation, with a focus on ongoing pathophysiological processes and the transition between inflammatory stages on one side and progressive states with neurodegeneration on the other. We introduce the pathophysiological hallmarks of neuroinflammation from tissue damage to reorganization, bridging the gap between studies performed in mouse models (in vivo and ex vivo) and investigations of humans with MS (in vivo imaging and electrophysiological data). We put these processes into a conceptual framework of brain network dynamics addressing new developments of cerebral circuit characterizations and computational neuroscience for the description of the brains transition through disease stages by the aid of neuroimaging and system electrophysiology. Finally, we link static and dynamic network dynamics related to neuroinflammation with clinical and functional outcome measures and actual therapeutic remedies to highlight important aspects for future studies and our conceptual understanding of MS as a chronic and progressive disease paving new ways to tackle neuroinflammation and neurodegeneration from the translational and clinical perspective.