In Vivo Magnetic Resonance Imaging of Embryonic Neural Grafts in a Rat Model of Striatonigral Degeneration (Multiple System Atrophy)

Abstract

The effects of embryonic neural transplantation in experimental models of neurodegenerative disorders are commonly assessed by behavioral tests and postmortem neurochemical or anatomical analysis. The purpose of the present study was to evaluate embryonic neuronal grafts in a novel rat model of multiple system atrophy (MSA) with the help of in vivo magnetic resonance imaging (MRI) and to correlate imaging with histological parameters. Striatonigral double lesions were created in male Wistar rats by unilateral intrastriatal injection of 3-nitropropionic acid (3-NP). Seven weeks following lesion surgery animals were divided into four transplantation groups receiving either pure mesencephalic, pure striatal, mesencephalic-striatal cografts, or sham grafts. In vivo structural imaging was performed 21 weeks after transplantation using a whole body 1.5 Tesla MR scanner. The imaging protocol comprised T2-weighted TSE and T1-weighted TIR sequences. Immunohistochemistry using DARPP-32 as striatal marker and tyrosinhydroxylase as marker for nigral neurons was performed for correlation analysis of imaging and histological parameters. The sensitivity of graft detection by in vivo MRI was 100%. The graft tissue was clearly demarcated from the remaining striatal tissue in both T2- and T1-weighted sequences. Morphometrically, cross-sectional areas of the grafts and spared intact striatum as defined by immunohistochemistry correlated significantly with measurements obtained by in vivo MRI. In conclusion, we were able to evaluate in vivo both lesion-induced damage and graft size in a 3-NP rat model of MSA using a conventional whole body 1.5 Tesla MRI scanner. Additionally, we obtained an excellent correlation between MRI and histological measurements.