TIME-COURSE OF THE NEUROPROTECTIVE EFFECT OF TRANSPLANTATION ON QUINOLINIC ACID-INDUCED LESIONS OF THE STRIATUM

Injection of quinolinic acid in the rat striatum mimics neurochemical changes observed in Huntington's disease. We previously demonstrated t hat intrastriatal transplantation of fetal striatum or gelfoam protect s against toxicity induced by a subsequent intrastriatal injection of quinolinic acid performed one week later, Herein, we examined whether fetal striatum or sham transplantation provides protection against qui nolinic acid that lasts up to four weeks. Intrastriatal quinolinic aci d injection produces neuronal loss and gliosis in Nissl staining, loss of cytochrome oxidase histochemical staining, decrease in autoradiogr aphic binding of [H-3]SCH 23390-labeled dopamine D1 and [H-3]CGS 21680 -labeled adenosine A2 receptors, and increase in autoradiographic bind ing of[H-3]PK 11195-labeled peripheral benzodiazepine binding sites, N one of these changes was observed in rats transplanted with fetal stri atum one, two or four weeks before quinolinic acid injection. In anima ls transplanted with fetal striatal tissue, Nissl staining showed heal thy grafts located in normal appearing striata. Although sham transpla ntation performed one week before quinolinic acid injection also prote cted against histological, histochemical and binding changes, sham tra nsplantation performed two or four weeks before quinolinic acid inject ion was less effective in attenuating quinolinic acid-induced striatal toxicity. Thus, sham transplantation provides transient protection ag ainst quinolinic acid-induced striatal toxicity, whereas implantation of tissue such as fetal striatum seems to be required for long-lasting protection. Our study suggests that intracerebral transplantation may also act through other mechanisms than restoration of deficient neuro transmitters or damaged pathways, a finding which may have significant clinical implications in assessing the potential benefit of this appr oach for the treatment of neurodegenerative disorders such as Huntingt on's disease.