The morphology, integration, and functional efficacy of striatal grafts differ between cell suspensions and tissue pieces.
In order to develop a surgical protocol for use in clinical trials of striatal transplantation in Huntington's disease (HD), the issues involved in the preparation and implantation of the embryonic striatal tissue must be addressed. Rodent models of HD offer the best experimental paradigm with which to study various aspects of striatal transplantation. In this article we present the results of an investigation of the role of trypsin and the process of trituration in the preparation of cell suspensions compared to the use of solid pieces of tissue. The embryonic material was derived from the lateral ganglionic eminence (LGE) and implanted into the excitotoxically lesioned striatum of the host rats. Twelve weeks following implantation, retrograde tracing of projections from the graft to the globus pallidus was performed. Grafts derived from cell suspensions triturated in the presence of trypsin contained larger quantities of striatal tissue within the graft and more DARPP-32-positive medium spiny neurons than grafts implanted as fragments of tissue. Afferent and efferent connectivity was also better in the trypsinized suspension graft group. Modest recovery in paw reaching was observed contralateral to the grafted side in animals implanted with solid fragments of embryonic striatal tissue. No relationship was observed between functional effect and the graft anatomy. These results suggest that local graft host interaction may also be involved in graft-mediated functional recovery.
Watts
C
C
MRC Cambridge Centre for Brain Repair, Department of Neurosurgery, University of Cambridge, UK. cwclw@msn.com
Brasted
P J
PJ
Dunnett
S B
SB
D000110:Acetylcholinesterase / Q000032:analysis / Q000276:immunology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced; D016380:Brain Tissue Transplantation / Q000379:methods*; D017690:Cell Transplantation / Q000379:methods*; D003342:Corpus Striatum / Q000166:cytology / Q000196:embryology / Q000637:transplantation*; D004195:Disease Models, Animal; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004525:Efferent Pathways; D005260:Female; D016332:Fetal Tissue Transplantation / Q000379:methods*; D005917:Globus Pallidus / Q000378:metabolism*; D006801:Humans; D006816:Huntington Disease / Q000601:surgery; D007150:Immunohistochemistry; D008124:Locomotion; D009419:Nerve Tissue Proteins; D009475:Neurons, Afferent / Q000166:cytology; D009476:Neurons, Efferent / Q000166:cytology; D010750:Phosphoproteins / Q000032:analysis / Q000276:immunology; D017378:Quinolinic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014357:Trypsin / Q000378:metabolism
D000662:Amphetamines; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D000110:Acetylcholinesterase; D014357:Trypsin; D017378:Quinolinic Acid