Brain activity changes in an animal model for multiple sclerosis can be highlighted by functional magnetic resonance imaging

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Magnetic Resonance Imaging (MRI) is used for MS first diagnosis and the evaluation of CNS damage extension during disease course while information about cortical area functional reorganization can be obtained by means of functional MRI (fMRI). The clinical patterns of disease evolution are highly variable and scarcely correlate with structural MRI-detected CNS damage. This phenomenon has been referred to as clinical/MRI paradox. Experimental Autoimmune Encephalomyelitis (EAE) is the animal model for MS and can be induced in Dark Agouti (DA) rat reproducing the condition experienced by the most MS patients, i.e. the remitting-relapsing form. fMRI observations in MS are already available in humans, but deeper knowledge on its usefulness might be gained using reliable animal models. EAE was induced by syngenic spinal cord intrafootpad administration with clinical disease onset around 10 days post EAE induction (dpi) and the worst clinical condition reached on 14dpi without a complete symptom resolution in main animals up to 45dpi. The brain plasticity was investigated by means of serial fMRI acquisitions performed before, 30 and 60 days after EAE induction. A train of squared pulses electrical stimulation (frequency=3Hz, current=2mA, duration=0.5ms) was delivered to the left forepaw during acquisition of MRI sensitive to Blood-Volume. A single stimulation protocol was composed of 30 images under rest condition and 10 images acquired during stimulation. After appropriate image analysis, performed using the FSL software package, the brain region activated by the applied stimulus was determined. The week before EAE induction, electrical stimulation resulted in a localized response only in the contralateral sensory motor cortex according to previously reported results. Thirty and 60dpi, the activated area was greatly increased covering large regions of both contra and ipsilateral somatosensory cortex and extending also to extra-cortical regions. Our results show that the DA rat EAE model is a good model in reproducing the functional reorganization of cortex observed in MS patients. It remains to be investigated whether this effect could represent an innovative platform for testing new therapeutic approaches for MS. AKNOWLEDGMENTS: The present work was partially supported by Fondazione Italiana Sclerosi Multipla (FISM) grant code 10/12/F14. We thank Dr Elisa Ballarini and Dr Virginia Rodriguez-Menendez for the image supply.