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Nitric Oxide-Containing Neurons in Long-Term Grafts in a Rat Model of Parkinson's Disease

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Abstract:

The role that nitric oxide may play in modulating graft function in long-term fetal ventral mesencephalic grafts in an animal model of Parkinson's disease was investigated. Mature grafts harvested from the entire fetal ventral mesencephalon possessed a large number of neuronal nitric oxide synthase (nNOS)/NADPH-diaphorase-containing neurons throughout the graft intermingled with dopaminergic neurons. The morphological and neurochemical characteristics of these NADPH-diaphorase neurons resembled those in centers adjacent to the substantia nigra of adult brain but not that of the striatum. Pretreatment with the nNOS blocker, 7-nitroindazole, resulted in contralateral rotations following methamphetamine challenge in long-term grafted animals that previously showed normalized rotational behavior. In contrast, mature grafts derived from fetal ventral mesencephalon without the midline areas possessed only a few nNOS-containing neurons within the grafts, and a similar methamphetamine challenge following 7-nitroindazole pretreatment in long-term grafted rats that previously showed normalized rotational behavior resulted in random movements. Our results indicate that nitric oxide-containing neurons inadvertently included during grafting may affect graft function, and excluding the midline areas of the ventral mesencephalon during tissue harvesting may minimize this effect.

Keywords: Dopamine; NADPH-diaphorase; Neural tissue transplantation; Nitric oxide synthase; Striatum; Ventral mesencephalon

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/000000007783464975

Affiliations: 1: Department of Anatomy & Cell Biology, University of Western Ontario, London, Ontario, Canada 2: Department of Anatomy & Cell Biology, University of Western Ontario, London, Ontario, Canada, Department of Psychiatry, University of Western Ontario, London, Ontario, Canada

Publication date: May 1, 2007

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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