title: Multitract microtransplantation increases the yield of DARPP-32-positive embryonic striatal cells in a rodent model of Huntington's disease.
abstract: Embryonic striatal graft-mediated functional recovery in the rodent lesion model of Huntington's disease (HD) has been shown to correlate with the proportion of dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein with a molecular weight of 32 kDa (DARPP-32)-positive  neurons in the graft. The current study investigated the impact of graft distribution on the yield of DARPP-32-positive cells in the grafts following either single-tract or multitract cell delivery protocols using the microtransplantation approach. Cells derived from the whole ganglionic eminence  of E15 rat embryos, ubiquitously expressing green fluorescent protein (GFP), were implanted into unilaterally QA-lesioned rat striatum either as 2 × 1.8 μl macrodeposits in a single tract, or as 18 × 0.2 μl microdeposits disseminated over six needle, multitract, penetrations.  For both groups, an ultrathin glass capillary with an outer diameter of 50 μm was used. Histological assessment at 4 months after transplantation showed nearly twofold increase of DARRP-32-positive striatal-like neurons in the multitract compared to the single-tract group. However, the  cellular make-up of the grafts did not translate into functional differences as tested in a basic spontaneous behavior test. Furthermore, the volumetric values for overall volume, DARPP-32-positive patches, and dopaminergic projection zones were similar between both groups. The results show  that distribution of fetal striatal tissue in multiple submicroliter deposits provides for an increased yield of striatal-like neurons, potentially due to the enlargement of the graft-host border area intensifying the graft's exposure to host-derived factors. Furthermore, the use of  embryonic tissue from GFP donors was validated in cell-based therapy studies in the HD model.
authors.affiliation: Laboratory of Molecular Neurosurgery, Department of Stereotactic and Functional Neurosurgery, Neurocentre, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Fabian
authors.initials: F
authors.lastname: Büchele
authors.forename: Anna
authors.initials: A
authors.lastname: Papazoglou
authors.forename: Máté
authors.initials: M
authors.lastname: Döbrössy
authors.forename: Guido
authors.initials: G
authors.lastname: Nikkhah
mesh_terms: D000818:Animals; D016380:Brain Tissue Transplantation; D003342:Corpus Striatum / Q000166:cytology* / Q000196:embryology*; D004195:Disease Models, Animal; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism*; D005260:Female; D006816:Huntington Disease / Q000378:metabolism / Q000628:therapy*; D009474:Neurons / Q000378:metabolism* / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32