Functional neuronal replacement by grafted striatal neurones in the ibotenic acid-lesioned rat striatum

Abstract

In rats, striatal neuronal destruction by so-called excitotoxic amino acids, kainic acid or ibotenic acid (IA) produce neuropathological and neurochemical changes in the basal ganglia^1–4 which resemble those seen in patients with Huntington's chorea^5,6. Such lesioned animals show a behavioural syndrome which is reminiscent of the cardinal symptoms of the disease^7–12, accompanied by a substantial increase in local cerebral metabolic activity in several striatal target structures within the extrapyramidal motor system^13–15. The study was designed to explore the potential of grafted fetal striatal neurones implanted into the IA-lesioned striatum to compensate for the structural, neurochemical, metabolic and behavioural defects of IA-lesioned rats. Extending previous studies^16,17, we report here that such striatal implants can significantly ameliorate the lesion-induced locomotor hyperactivity and at least partly normalize the metabolic hyperactivity in the extrapyramidal neuronal system.