A comparison of solid intraventricular and dissociated intraparenchymal fetal substantia nigra grafts in a rat model of Parkinson's disease: impaired graft survival is associated with high baseline rotational behavior

Abstract

It has been established that substantia nigra (SN) grafts can produce a behavioral effect in animal models of Parkinson's disease when transplanted either into the lateral ventricles as solid tissue fragments or directly into the striatum as dissociated cells. These two transplantation methods (solid-intraventricular and dissociated-intraparenchymal) were directly compared in the present study. Adult male rats received unilateral SN lesions by stereotaxic injection of 6-hydroxydopamine. Fetal ventral mesencephalon, containing the SN, was harvested from 15-day gestational rat fetuses. Equal weights of tissue were transplanted, either as solid-intraventricular or dissociated-intraparenchymal grafts. In the animals with surviving grafts, similar decreases in apomorphine-induced rotational behavior were seen in both dissociated (40.2% at 6 weeks, 29.6% at 12 weeks, N = 12) and solid (31.8% at 6 weeks, 51.0% at 12 weeks, N = 11) graft groups. Control animals receiving tectal grafts showed smaller decreases (dissociated: 12.6% at 6 weeks, 18.8% at 12 weeks, N = 20; solid: 4.1% at 6 weeks, 8.0% at 12 weeks, N = 20). There were no significant overall differences between the effects of the solid and dissociated grafts; however, in the subgroup of animals with high baseline levels of rotational behavior, the solid-intraventricular grafts produced a significantly larger effect then did the dissociated-intraparenchymal SN grafts. There was also a tendency for the effect of the solid-intraventricular grafts to increase gradually over the 12-week testing period, whereas the effects of the dissociated-intraparenchymal grafts were maximal by 6 weeks after transplantation. For both SN graft groups, there were significant correlations between decreases in rotation and numbers of surviving tyrosine hydroxylase-immunoreactive neurons in the grafts. It was also found that animals with no surviving transplanted tyrosine hydroxylase-positive neurons had higher baseline levels of rotational behavior. Therefore, in the present model, solid-intraventricular and dissociated-intraparenchymal SN grafts have similar effects on apomorphine-induced rotational behavior, except that the solid-intraventricular grafts tended to produce a larger effect in animals with high baseline levels of rotational behavior.