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

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 invivo. The aim of this study was to characterize the time course of the nigral lesion invivo, 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 14days 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 invivo, 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. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
This work was partially supported by a grant from the Fondo de Investigaciones Sanitarias (FIS08/0060 and PS09/00527) from the Ministerio de Sanidad y Consumo and SAF2009-0807 from the Ministerio de Ciencia e Innovacion, Spain. CIBERBBN is an initiative funded by the VI National R&D&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, and CIBER Actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. G. S. has a JAE-Doc contract from CSIC.