Effects of severity of host striatal damage on the morphological development of intrastriatal transplants in a rodent model of Huntington's disease: implications for timing of surgical intervention.
OBJECTIVE
The goal of this study was to investigate the effect of the severity of host neural damage on the morphological development of intrastriatal transplants in a rodent model of Huntington's disease.


METHODS
Sprague-Dawley rats were subjected to unilateral striatal lesioning induced by administration of quinolinic acid (20 nM, 40 nM, or 90 nM). Seven days postlesioning, intrastriatal cell suspension grafts were placed in the right striatum in some of these animals. Grafts were also placed in the right striatum of additional animals that had not been subjected to lesioning. The rats were killed and processed for morphological analysis 8 weeks after grafting. The results indicate that striatal grafts survive and grow much better when implanted into a lesioned striatum rather than into an intact striatum, as measured both by the volume and the numbers of medium-sized spiny neurons within the graft. Only a small or modest lesion is necessary to produce this effect. By some measures (such as graft volume) grafts survive less well when the lesion is more extensive. The presence of a graft reduced the extent of striatal atrophy induced by the lesions, but this effect was not caused by differences in the numbers of surviving neurons per se.


CONCLUSIONS
These results have significant implications for the timing of surgical intervention and patient selection with respect to current and future clinical trials of striatal transplantation in the treatment of Huntington's disease.
Academic Department of Neurosurgery and MRC Cambridge Centre for Brain Repair, University of Cambridge, United Kingdom.
C
C
Watts
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SB
Dunnett
D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D001284:Atrophy; D002452:Cell Count; D002470:Cell Survival; D017690:Cell Transplantation; D003342:Corpus Striatum / Q000166:cytology / Q000473:pathology* / Q000637:transplantation; D004195:Disease Models, Animal; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004791:Enzyme Inhibitors / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006816:Huntington Disease / Q000473:pathology* / Q000601:surgery; D009410:Nerve Degeneration / Q000473:pathology / Q000601:surgery; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000473:pathology; D010750:Phosphoproteins / Q000032:analysis; D017378:Quinolinic Acid / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D014446:Tyrosine 3-Monooxygenase; D000110:Acetylcholinesterase; D017378:Quinolinic Acid