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A Novel, Non-invasive Model for Studying Myelin Repair

Presenters Name: 
James Woznak
Co Presenters Name: 
Primary Research Mentor: 
Kevin Lee
Secondary Research Mentor: 
9:30 - 10:15
Time of Presentation: 
2019 - 9:30am to 10:15am
Newcomb Hall Ballroom
Presentation Type: 
Presentations Academic Category: 
Grant Program Recipient: 
Harrison Undergraduate Research Grant

Currently available animal models of myelin repair for diseases like Multiple Sclerosis are useful, but each possesses fundamental limitations. This current project designed, developed, and tested a novel model for studying myelin repair that circumvents the need for direct intracranial injections and/or the production of massive systemic inflammation that other models require. As well as allowing for longitudinal monitoring of a detailed time course of demyelination and remyelination in individual animals. Magnetic Resonance Imaging-guided Focused Ultrasound (MRgFUS) in conjunction with intravenously-administered microbubbles was used to focally and transiently open the Blood Brain Barrier in the subcortical white matter. An AMPA receptor agonist, AMPAhb, was administered intravenously. When administered intravenously the neurotoxin is able to only access the target of sonication, producing focal demyelination. Diffusion Tensor Imaging (DTI) was used to monitor the time courses via change of Mean Diffusivity (MD) and Radial Diffusivity (RD), both of which are DTI scalars that are inversely related to myelination. Increases in MD and RD in the targeted area, consistent with demyelination was observed over the first two weeks post FUS. This is followed by a return MD and RD to baseline level, consistent with remyelination. This model has several distinct advantages for the study of myelin repair. Compared to other available models, is non-invasive and also allows for characterization of the mechanistic underpinnings of myelin repair and for testing of candidate therapeutics for myelin repair, providing greater precision and a more focused assessment of remyelination mechanisms.