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Diffusion parameters in the striatum of rats with 6-hydroxydopamine-induced lesions and with fetal mesencephalic grafts.
Reum T, Olshausen F, Mazel T, Vorisek I, Morgenstern R, Sykova E.
Institute of Pharmacology and Toxicology, Medical Faculty (Charite), Humboldt-University, Berlin, Germany.
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. Copyright 2002 Wiley-Liss, Inc.
