Diffusion parameters in the striatum of rats with 6-hydroxydopamine-induced lesions and with fetal mesencephalic grafts.

Abstract

Functional recovery after transplantation of dopaminergic cells into the lesioned striatum is dependent on widespread diffusion of the transmitter released by the graft. In the present study, we investigated the diffusion parameters of the extracellular space in the striatum of control, 6-hydroxydopamine-lesioned, intrastriatally grafted, and sham-grafted rats in vivo. We used two types of grafts-single macrografts or multiple micrografts. The real-time iontophoretic tetramethylammonium method enabled us to extract three extracellular space diffusion parameters: volume fraction, alpha, tortuosity, lambda, and nonspecific uptake of tetramethylammonium, k'. Compared with controls (alpha = 0.19, lambda = 1.59), in lesioned animals both alpha and lambda were lower (alpha = 0.14, lambda = 1.50). alpha and lambda were increased inside macro-and micrografts, where alpha = 0.24 and lambda = 1.80, and in sham-grafted areas, where alpha = 0.24 and lambda = 1.72. In regions outside the grafts (alpha = 0.15, lambda = 1.51) or in sham grafts (alpha = 0.14, lambda = 1.49), the values of alpha and lambda were similar to the values observed in lesioned striatum. Nonspecific uptake (k') did not differ among the groups. Our results show that, compared with control, alpha and lambda were decreased in dopamine-depleted areas and increased in areas with grafts. Multiple but smaller graft deposits, in contrast to their enlarged capability for dopaminergic reinnervation, impair the conditions for diffusion and extrasynaptic transmission in a larger area of the striatum than do single macrografts, presumably because of more extensive tissue damage, cell loss, and astrogliosis.