Neural progenitor implantation restores metabolic deficits in the brain following striatal quinolinic acid lesion.

Abstract

Neural progenitor transplantation is a potential treatment for neurodegenerative diseases, including Huntington's disease (HD). In the current study, we tested the potential of rat embryonic neural progenitors expanded in vitro as therapy in the rat quinolinic acid-lesioned striatum, a model that demonstrates some of the pathological features of HD. We used positron emission tomography (PET) to demonstrate that the intrastriatal injection of cultured rat neural progenitors results in improved metabolic function in the striatum and overlying cortex when compared to media-injected controls. Transplanted progenitors were capable of surviving, migrating long distances and differentiating into neurons and glia. The cortices of transplanted animals contained greater numbers of neurons in regions that had shown metabolic improvement. However, histological analysis revealed that only a small fraction of these increased neurons could be accounted for by engrafted cells, indicating that the metabolic sparing was likely the result of a trophic action of the transplanted cells on the host. Behavioral testing of the implanted animals did not reveal improvement in apomorphine-induced rotation. These data demonstrate that progenitor cell implantation results in enhanced metabolic function and sparing of neuron number, but that these functions do not necessarily result in the restoration of complex circuitry.