Neuroinflammation and its Contribution to Cortical Tissue Damage and Repair

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Current pharmacological agents available for the treatment of multiple sclerosis, while being efficient at reducing the acute manifestations of the disease, generally fail to prevent accumulation of irreversible disability. Lately, there has been increasing effort for testing novel therapies that could protect the brain in multiple sclerosis from developing irreversible damage and even promote the repair of myelin. Myelin is the protective coating around nerve fibers in the central nervous system and the main “target” of the immune attack in multiple sclerosis.

Scientists have discovered that, to some extent, myelin may heal naturally, especially in the cortex. It has also been hypothesized that this healing process may be, at least in part, promoted by “activated” microglia. Microglia are the primary immune cells of the central nervous system, and are involved in overall brain surveillance and maintenance, including defense against infections, and cleaning of cell debris, and damaged proteins after stress or tissue damage. When a brain insult is detected, microglia cells undergo a series of functional and structural changes and become “activated.” Activated microglia upregulate expression of the 18kDa translocator protein (TSPO), which can be imaged in vivo by selective positron emission tomography (PET) TSPO radioligands.

Using simultaneous magnetic resonance-PET (MR-PET) imaging with 11C-PBR28, a novel, second-generation TSPO radiotracer, and ultra high field 7 Tesla (T) MRI, we demonstrated abnormally high 11C-PBR28 binding in the cortex and in cortical lesions of patients with MS, indicating the presence of abnormally activated glial cells. Our current goal is to combine 11C-PBR28 MR-PET with 7T imaging to investigate in patients with aggressive cortical disease the presence of neuroinflammation and its contribution to cortical demyelination and cortical tissue repair.

Selected publications:

1) Herranz E, Giannì C, Louapre C, Treaba CA, Govindarajan ST, Ouellette R, Loggia M, Sloane J, Madigan N, Izquierdo-Garcia D, Ward N, Mangeat G, Granberg T, Klawiter EC, Catana C, Hooker JM, Taylor N, Ionete C, Kinkel RP, Mainero C. The neuroinflammatory component of gray matter pathology in multiple sclerosis. Ann Neurol. 2016 Sep 30. doi: 10.1002/ana.24791. PMID: 27686563.

2) Koudriavtseva T, Mainero C. Neuroinflammation, neurodegeneration and regeneration in multiple sclerosis: intercorrelated manifestations of the immune response. Neural Regeneration Research. November 2016,Volume 11, Issue 11 1727- 1730. doi: 10.4103/1673-5374.194804.