title: In vivo magnetic resonance imaging characterization of bilateral structural changes in experimental Parkinson's disease: a T2 relaxometry study combined with longitudinal diffusion tensor imaging and manganese-enhanced magnetic resonance imaging in the 6-hydroxydopamine rat model.
abstract: The neuropathological hallmark of Parkinson's disease is the loss of dopaminergic neurons in the pars compacta of the substantia nigra (SNc). The degenerative process starts unilaterally and spreads to the dopaminergic system of both hemispheres. However, the complete characterization of the nigra lesion and the subsequent changes in basal ganglia nuclei activity has not yet been achieved in vivo. The aim of this study was to characterize the time course of the nigral lesion in vivo, using longitudinal T2 relaxometry and diffusion tensor imaging, and the changes in basal ganglia nuclei activity, using manganese-enhanced magnetic resonance imaging, in 6-hydroxydopamine (6-OHDA)-lesioned rats. Our results showed that a unilateral SNc lesion induces bilateral alterations, as indicated by the enhancement of magnetic resonance imaging T2 relaxation times in both the ipsilateral and contralateral SNc. Moreover, axial and radial diffusivities demonstrated bilateral changes at 3 and 14 days after 6-OHDA injection in the pars reticulata of the substantia nigra and cortex, respectively, in comparison to the sham group, suggesting bilateral microstructural alterations in these regions. Unexpectedly, manganese-enhanced magnetic resonance imaging showed decreased axonal transport from the ipsilateral subthalamic nucleus to the ventral pallidum in 6-OHDA-lesioned animals compared with the sham group. These findings demonstrate, for the first time in vivo, the temporal pattern of bilateral alteration induced by the 6-OHDA model of Parkinson's disease, and indicate decreased axonal transport in the ipsilateral hemisphere.
authors.affiliation: Department of Brain Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona, Barcelona, Spain. gsrfat@iibb.csic.es
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Soria
authors.forename: Esther
authors.initials: E
authors.lastname: Aguilar
authors.forename: Raúl
authors.initials: R
authors.lastname: Tudela
authors.forename: Joaquim
authors.initials: J
authors.lastname: Mullol
authors.forename: Anna M
authors.initials: AM
authors.lastname: Planas
authors.forename: Concepció
authors.initials: C
authors.lastname: Marin
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal / Q000502:physiology; D002712:Chlorides / Q000378:metabolism*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D017895:Manganese Compounds / Q000378:metabolism*; D016627:Oxidopamine / Q000009:adverse effects*; D010300:Parkinson Disease / Q000473:pathology*; D020734:Parkinsonian Disorders / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002712:Chlorides; D050483:Dopamine Plasma Membrane Transport Proteins; D017895:Manganese Compounds; D016627:Oxidopamine; C025340:manganese chloride