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Abstract Details

Detection of Microglia Activation in the Theiler’s Murine Encephalomyelitis Virus Model of Chronic Demyelination Using Ultra-Small Superparamagnetic Iron Oxides (USPIO) Nanoparticle Enhanced High-Field Imaging
Multiple Sclerosis
S49 - Multiple Sclerosis: Basic Science (1:12 PM-1:24 PM)
002
To investigate temporal pattern of microglia activation in Theiler’s Murine Encephalomyelitis Virus (TMEV) mice model of chronic demyelination by using ultra-small superparamagnetic iron oxides (USPIO) nanoparticles enhanced imaging on 9.4T brain MRI. 

Blood-derived monocytes can be labeled with USPIO at periphery and subsequently migrate into areas of microglia activation in the brain.

Fifteen (15) SJL mice (Envigo, Indianapolis, IN) were injected with TMEV (n=12) or saline injection (n=3) at 7 weeks of age. MRI and behavioral testing was performed at 3 months post infection (mpi) (the peak of inflammatory phase), at 4 mpi, 5 mpi and 7 mpi (throughout neurodegenerative phase) using T2* weighted gradient echo MRI, performed 24 hours after USPIO injection. Contrast enhancing lesion (CEL) number and volume were measured and development of brain atrophy was assessed at all serial timepoints. Disease progression was measured by clinical disability score (CDS) and performance on RotaRod.
CEL were detected in total of 6 TMEV mice and none of the controls. CEL number and volume increased significantly from 3mpi to 7mpi (p<0.01). A total of 10, 2, 20 and 66 CEL were detected at 3mpi, 4mpi, 5mpi and 7mpi, respectively. Greater CEL number (r=0.7, p=0.008 and r=0.8, p=0.002) and volume (r=0.67, p=0.012 and r=0.79, p=0.002) at 5 and 7 mpi, respectively, were significantly related to higher CDS. Greater CEL number (r=-0.56, p=0.035) and volume (r=-0.58, p=0.031) at 5mpi, were significantly related to lower score on RotaRod. CEL number and volume at 3mpi were significantly associated with decrease in cortical (p<0.05) and increase in lateral ventricle volumes (p<0.01) across all serial time points. 

Greater CEL number and volume was related to more severe TMEV disease. Serial USPIO imaging is a promising biomarker for investigating the effect of therapeutic interventions on microglia activation and neurodegeneration in TMEV mice.

 
Authors/Disclosures
Robert Zivadinov, MD, PhD, FAAN (Buffalo Neuroimaging Analysis Center)
PRESENTER 		The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Omnicuris. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Myrobalan. Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bristol Myers Squibb. The institution of Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen.
Ferdinand Schweser, PhD (SUNY University At Buffalo) Dr. Schweser has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier.
Michael G. Dwyer III, MD, PhD (Buffalo Neurological Analysis Center) Dr. Dwyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Dwyer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Keystone Heart, Ltd. Dr. Dwyer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Dwyer has received research support from Novartis. The institution of Dr. Dwyer has received research support from Keystone Heart, Ltd. The institution of Dr. Dwyer has received research support from Bristol Myers Squibb. The institution of Dr. Dwyer has received research support from Roche.
Suyog U. Pol, PhD (University At Buffalo - CTRC) Dr. Pol has nothing to disclose.