Evaluation of the therapeutic effects of mesenchymal stem cell transplantation in rat model of Parkinson's disease using 1.5T MRS

Abstract

Purpose: Using 1.5 T proton magnetic resonance spectroscopy (1H-MRS) with high resolution 23mm special coil in vivo to monitor the metabolic changes of the nerves in the striatum of Parkinson's disease (PD) rat before and after mesenchymal stem cells (MSCs) transplantation, in result to explore the value of 1.5T clinical MR spectral analysis in evaluating the therapeutic effects of MSCs transplantation. Materials and methods: Thirty cases of normal rats were treated as Parkinson's disease models with unilateral symptom by taking 6-hydroxydopamine (6-OHDA) to enforce unilateral (right) lesion, and 26 cases were successful. 1H-MRS was performed in the vivo rats using Philips 1.5T two gradients clinical MR machine with high resolution 23mm special coil on the three weeks point after lesion establishment, and on the three, six and nine weeks points after MSCs and serum-free medium injected respectively. The changes of NAA/Cr, Cho/Cr ratio in the bilateral striatum were analyzed. Meanwhile, the rat behavior was detected. The expression characteristics of tyrosine hydroxylase (TH) were checked in substantia nigra and the migration of the transplanted cells were observed using immunocytochemical and immunofluorescent methods. Results: At 6 weeks and 9 weeks points after MSCs transplanted, NAA/Cr ratios increased gradually in striatum of the damage side (right) comparing with the control group, and significant difference was showed between them (P<;0.05). At nine-week point after MSCs transplantation, NAA/Cr ratio was higher than that at six weeks point (P<;0.05). Cho/Cr ratios on the damaged side in MSCs transplantation group was lower than control group at 3, 6, 9 weeks points respectively (P<;0.05), but no significant difference was shown among 3, 6, 9 weeks points (P> 0.05). NAA/Cr ratios and Cho/Cr ratios in damaged side of MSCs transplantation group decreased comparing with their opposite parts respectively (P<;0.05). The number of rat's full rotations at 6 weeks and 9 weeks points after MSCs transplanted gradually showed a significant reduction compared with other rats (P<;0.05). The survival rates of TH-positive cells in the damage side striatum among two injected groups were no significant difference (P>0.05). However, by immunofluorescence staining, a part of BrdU labeled MSCs showed GFAP-positive, which conduced to the function of nerves repairing. Conclusion: As a non-invasive examination method in vivo, 1.5T 1H-MRS can be used to monitor the metabolic changes dynamically in the striatum of PD rat model after MSCs transplantation, that was able to evaluate the therapeutic effects efficiently.