TY - JOUR
T1 - Functional magnetic resonance imaging of rats with experimental autoimmune encephalomyelitis reveals brain cortex remodeling
AU - Tambalo, Stefano
AU - Peruzzotti-Jametti, Luca
AU - Rigolio, Roberta
AU - Fiorini, Silvia
AU - Bontempi, Pietro
AU - Mallucci, Giulia
AU - Balzarotti, Beatrice
AU - Marmiroli, Paola
AU - Sbarbati, Andrea
AU - Cavaletti, Guido
AU - Pluchino, Stefano
AU - Marzola, Pasquina
PY - 2015/7/8
Y1 - 2015/7/8
N2 - Cortical reorganization occurring in multiple sclerosis(MS)patients isthoughtto playakeyrole in limiting the effect of structural tissuedamage. Conversely, its exhaustionmaycontribute to the irreversible disability that accumulates with disease progression. Several aspects of MS-related cortical reorganization, including the overall functional effect and likely modulation by therapies, still remain to be elucidated. The aim of this work was to assess the extent of functional cortical reorganization and its brain structural/pathological correlates in Dark Agouti rats with experimental autoimmune encephalomyelitis (EAE), a widely accepted preclinical model of chronic MS. Morphological and functional MRI (fMRI) were performed before disease induction and during the relapsing and chronic phases of EAE. During somatosensory stimulation of the right forepaw, fMRI demonstrated that cortical reorganization occurs in both relapsing and chronic phases of EAE with increased activated volume and decreased laterality index versus baseline values. Voxel-based morphometry demonstrated gray matter (GM) atrophy in the cerebral cortex, and both GM and white matter atrophy were assessed by ex vivo pathology of the sensorimotor cortex and corpus callosum. Neuroinflammation persisted in the relapsing and chronic phases, with dendritic spine density in the layer IV sensory neurons inversely correlating with the number of cluster of differentiation 45-positive inflammatory lesions. Our work provides an innovative experimental platform that may be pivotal for the comprehension of key mechanisms responsible for the accumulation of irreversible brain damage and for the development of innovative therapies to reduce disability in EAE/MS.
AB - Cortical reorganization occurring in multiple sclerosis(MS)patients isthoughtto playakeyrole in limiting the effect of structural tissuedamage. Conversely, its exhaustionmaycontribute to the irreversible disability that accumulates with disease progression. Several aspects of MS-related cortical reorganization, including the overall functional effect and likely modulation by therapies, still remain to be elucidated. The aim of this work was to assess the extent of functional cortical reorganization and its brain structural/pathological correlates in Dark Agouti rats with experimental autoimmune encephalomyelitis (EAE), a widely accepted preclinical model of chronic MS. Morphological and functional MRI (fMRI) were performed before disease induction and during the relapsing and chronic phases of EAE. During somatosensory stimulation of the right forepaw, fMRI demonstrated that cortical reorganization occurs in both relapsing and chronic phases of EAE with increased activated volume and decreased laterality index versus baseline values. Voxel-based morphometry demonstrated gray matter (GM) atrophy in the cerebral cortex, and both GM and white matter atrophy were assessed by ex vivo pathology of the sensorimotor cortex and corpus callosum. Neuroinflammation persisted in the relapsing and chronic phases, with dendritic spine density in the layer IV sensory neurons inversely correlating with the number of cluster of differentiation 45-positive inflammatory lesions. Our work provides an innovative experimental platform that may be pivotal for the comprehension of key mechanisms responsible for the accumulation of irreversible brain damage and for the development of innovative therapies to reduce disability in EAE/MS.
KW - Cortical reorganization
KW - Experimental autoimmune encephalomyelitis
KW - Functional magnetic resonance imaging
KW - Multiple sclerosis
KW - Neuroimmunology
KW - Rain plasticity
UR - http://www.scopus.com/inward/record.url?scp=84936864771&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84936864771&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0540-15.2015
DO - 10.1523/JNEUROSCI.0540-15.2015
M3 - Article
C2 - 26157006
AN - SCOPUS:84936864771
VL - 35
SP - 10088
EP - 10100
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 27
ER -