HEMA/MMMA microcapsule implants in hemiparkinsonian rat brain:: biocompatibility assessment using [3H]PK11195 as a marker for gliosis

被引:29
作者
Campioni, EG
Nobrega, JN
Sefton, MV [1 ]
机构
[1] Univ Toronto, Dept Chem Engn & Appl Chem, Toronto, ON M5S 1A4, Canada
[2] Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A4, Canada
[3] Clarke Inst Psychiat, Neuroimaging Res Sect, Toronto, ON M5S 1A4, Canada
基金
英国医学研究理事会;
关键词
dopamine; polymer encapsulation; Parkinson's disease; PC12; cells; striatum; autoradiography; H-3]PK11195; gliosis; biocompatibility;
D O I
10.1016/S0142-9612(97)00241-X
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Microencapsulation of dopamine-secreting cells in biocompatible, semi-permeable polymer membranes has been proposed as an alternative strategy for dopamine replacement for Parkinson's disease. In order to assess the viability of this proposal, dopamine-secreting PC12 cells were immunoisolated via microencapsulation in a 75:25 2-hydroxyethyl methacrylate/methyl methacrylate (HEMA/MMA) copolymer. A submerged nozzle-liquid jet method was used to produce small diameter (400 mu m) microcapsules, which were stereotaxically implanted in the denervated striatum of hemi-Parkinsonian rats. A 96% survival rate was associated with the implantation surgery and no deleterious side effects were apparent. Light microscopy revealed good biocompatibility between the HEMA/MMA copolymer and the host brain, as evidenced by the absence of gross tissue damage at the neuronal tissue/capsule interface. Autoradiographic analyses using [H-3]PK11195 as marker for reactive astrocytes revealed a moderate inflammatory response, confined to the immediate vicinity of the injection tract. Quantitative analyses indicated that the local tissue response did not differ significantly between brains implanted with PC12-containing capsules and those implanted with vehicle-containing capsules. Taken together, these results support the biocompatibility of HEMA/MMA copolymer as well as the feasibility and safety of stereotaxic implantation of microcapsules. (C) 1998 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:829 / 837
页数:9
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