Catecholamine-containing biodegradable microsphere implants as a novel approach in the treatment of CNS neurodegenerative disease |
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Authors: | A McRae E A Ling S Hjorth A Dahlström D Mason T Tice |
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Institution: | 1. Department of Anatomy and Cell Biology, University of G?teborg, Medicinaregatan 3–5, 41390, G?teborg, Sweden 2. Dept. of Anatomy, National University of Singapore, 0511, Singapore 3. Department of Pharmacology, University of G?teborg, Medicinaregatan 3–5, 41390, G?teborg, Sweden 4. Southern Research Institute, 35205, Birmingham, AL
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Abstract: | Biodegradable controlled-release microsphere systems made with the biocompatible biodegradable polyester excipient poly (dl-lactide-co-glycolide) constitute an exciting new technology for drug delivery to the central nervous system (CNS). Implantable
controlled-release microspheres containing dopamine (DA) or norepinephrine (NE) provide a novel means to compare DA- or NE-induced
restitution of function in unilateral 6-hydroxydopamine lesioned rats. A suspension of 3 μL of DA- or NE-containing microspheres
or empty microspheres was implanted in 2 sites of the DA denervated striatum of rats previously unilaterally lesioned with
6-hydroxydopamine. Contralateral-rotational behavior induced by apomorphine was used as an index of lesion success and, following
implantation of the microspheres, also as an index of functional recovery. Interestingly, both DA- and NE-microsphere-implanted
rats displayed a 30–50% reduction in the number of apomorphine-induced rotations up to 8 wk postimplantation. Rats implanted
with empty microspheres did not demonstrate significant changes in contralateral rotational behavior. Behavioral studies following
implantation of a mixture of DA and NE microspheres revealed an 80% decrease in the number of apomorphine induced rotations
up to 4 wk. On conclusion of the studies, immunocytochemical examination revealed growth of DA and tyrosine hydroxylase immunoreactive
fibers in the striatum of DA and NE microsphere-implanted rats. Functional behavior appeared to correlate with the degree
of fiber growth. Preliminary electron microscopic studies showed signs of axonal sprouting in the vicinity of the implanted
microspheres. No growth was noted in rats implanted with empty microspheres. This report reviews the abilities of both microencapsulated
NE and DA to assure functional recovery and to promote DA fiber (re)growth in parkinsonian rats. This novel means to deliver
these substances to the central nervous system could be of therapeutic usefulness in Parkinson's disease. |
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Keywords: | Microencapsulated catecholamines dl-lactide-co-glycolide)" target="_blank">poly(dl-lactide-co-glycolide) experimental hemi-Parkinsonism in rats striatum apomorphine 6-hydroxydopamine dopamine fiber growth |
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