Donor age dependent graft development and recovery in a rat model of Huntington’s disease: histological and behavioral analysis

Hochschulschrift

Abstract: Neural cell replacement therapy using fetal striatal cells has been shown to have disease modifying capacity in clinical trials in Huntington’s disease (HD) patients, although the results have been inconsistent. One of the contributing factors to the variable outcome could be the different repair potential of the range of donor ages used. The current study investigated the proliferation and differentiation potential of different donor ages in culture as well as, based on the rodent lesion model of HD, how intrastriatal- striatal grafts from variable aged donors develop in- vivo and how they influence functional recovery after.
For the in- vitro characterization primary cell cultures of whole ganglionic eminence (WGE) from donors of embryonic developmental age E13, E14, or E15 were exposed to different conditions and afterwards immunohistochemical characterized.
For the in- vivo study young adult female Sprague-Dawley rats were lesioned unilaterally in the dorso-striatum with quinolinic acid (0.12M) and transplanted 14 days later with single cell suspension grafts equivalent of one WGE from donors at age E13, E14, or E15; animals with or without striatal lesion served as controls. All animals were tested on the Cylinder and the Corridor tests, as well as on apomorphine-induced rotation at baseline, post-lesion/ pre-grafting, and at 6 and 10 weeks post-grafting.
In summary, the data demonstrates that the age of the embryonic donor tissue has an impact on the cellular composition in-vitro, in vivo cellular composition of the striatal transplant and on the graft mediated functional recovery. E13 tissue gave the best overall outcome respectively these three aspects indicating that WGE from different donor ages have different potential to promote functional recovery. Understanding the stages and process in rodent striatal development could improve tissue selection in clinical trials of cell therapy in HD

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: cc_by_nc_nd http://creativecommons.org/licenses/by-nc-nd/4.0/deed.de cc ; Albert-Ludwigs-Universität Freiburg, Dissertation, 2017

Classification and Topics

• Keyword: Huntington-Chorea ; Corpus striatum ; Tiermodell ; Zellkultur ; Chinolinsäure ; Biopharmazie ; Pharmakodynamik ; Pharmakokinetik

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2017
• Creator: Capetian, Stefanie
• Contributor: Nikkhah, Guido ; Klinik für Neurochirurgie. Freiburg im Breisgau ; Klinik für Neurochirurgie. Abteilung Stereotaktische und Funktionelle Neurochirurgie ; Albert-Ludwigs-Universität Freiburg. Medizinische Fakultät ; Albert-Ludwigs-Universität Freiburg

Further information

• DOI: 10.6094/UNIFR/12902
• URN: urn:nbn:de:bsz:25-freidok-129022
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:23 AM CEST