Аннотация
Intrastriatal implantation of a dopaminergic cell line surrounded
by a permeable, thermoplastic membrane was investigated as a method
of long-term dopamine (DA) delivery within the central nervous system
(CNS). An increase in DA release from PC12 cell-loaded capsules maintained
in vitro was associated with an increase in mitotic activity of the
encapsulated cell line. A significant reduction in apomorphine-induced
rotational behavior was observed after PC12 cell-containing capsules
were implanted into unilaterally 6-hydroxydopamine (6-OHDA) lesioned
rats, which was sustained for 24 wk. Four wk after implantation,
microdialysis studies revealed the presence of DA near PC12 cell-containing
capsules, which was comparable to extracellular striatal levels of
unlesioned controls. Extracellular striatal DA was undetectable by
microdialysis in lesioned animals near empty polymer capsules. Histological
analysis after 24 wk in vivo demonstrated that encapsulated PC12
cells survived, continued to express tyrosine hydroxylase, and that
encapsulation prevented tumorigenesis. The data suggested that the
release of a diffusible substance, most likely DA, from an implant
is sufficient to exert a long-term functional influence upon 6-OHDA
unilaterally lesioned rats and that capsules containing DA-secreting
cells may be an effective method of long-term DA delivery in the
CNS.
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