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Open Access Brain Repair in a Unilateral Rat Model of Huntington’s Disease: New Insights Into Impairment and Restoration of Forelimb Movement Patterns

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Abstract:

Huntington’s disease (HD) produces severe neurodegeneration in the striatum leading to disabling motor impairments, including the loss of control of skilled reaching movements. Fetal GABAergic transplants can physically replace the lost striatal cells but with only partial success in functional recovery. Here, we aimed to determine the extent and quality of the repair produced by fetal cell transplantation through an in-depth analysis of reaching behavior in the quinolinic acid-lesioned rat model of HD. Control, quinolinic acid-lesioned plus sham graft, and quinolinic acid-lesioned plus graft groups of rats were assessed in skilled reaching performance prior to and following lesion surgery and 3 months following injection of 400,000 fetal whole ganglionic eminence-derived cells into the striatum. This was compared to their performance in two more rudimentary tests of motor function (the adjusting step and vibrissae-evoked hand-placing tests). Grafted rats demonstrated a significant improvement in reaching success rate (graft +59%, shamTX +3%). Importantly, the quality of reaching behavior, including all components of the movement, was fully restored with no identifiable differences in the normal behavior shown by control rats. Postmortem immunohistochemical examination verified the survival of large intrastriatal grafts, and Fluoro-Gold tracing indicated appropriate outgrowth to the globus pallidus. Our study illustrates for the first time the detailed analysis of qualitative improvement of motor function following brain repair in a rat model of HD. The results demonstrate significant improvements not only in gross movements but also in the skilled motor patterns lost during HD. Fetal GABAergic cell transplantation showed a demonstrable ability to restore motor function to near normal levels, such that there were few differences from intact control animals, an effect not observed in standard tests of motor function.

Keywords: Adjusting step test; Fluoro-Gold (FG); Skilled reaching; Spontaneous behavior; Transplantation; Vibrissae-evoked hand-placing test; Whole ganglionic eminence (wGE)

Document Type: Research Article

DOI: https://doi.org/10.3727/096368912X657918

Publication date: 2013-10-04

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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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