Intraparenchymal fetal striatal transplants and recovery in kainic acid lesioned rats

Abstract

Striatal kainic acid (KA) lesions induce behavioral and biochemical deficits which resemble symptoms encountered in patients suffering from Huntington's disease. In rats with KA lesions, fetal striatal transplants have shown to reverse the pervasive nocturnal hyperactivity induced by the lesion. In the present study 4.6 mm 3 of fetal striatal tissue were delivered bilaterally into the anterodorsal portion of the lesioned caudate nucleus. Care was taken to deliver the transplant within the host parenchyma and away from the lateral ventricles. Locomotor behavior analyzed using the Digiscan animal activity monitors before and after the transplants demonstrated a reversal of the hyperactivity following transplants in 70% of lesioned animals. Microinjections of horseradish peroxidase delivered into the globus pallidus and substantia nigra of a small group of functionally recovered transplanted animals, did not reveal evidence for reinnervation between host nigra or pallidum and the transplant at 10 weeks post-transplantation. Other laboratories have reported anatomical connections by 6 months post-transplantation. Ventricular/brain ratios demonstrated that intraparenchymal transplants significantly reduced the ventricular dilation following KA lesion. These results suggest that functional recovery can be obtained when the transplant is immersed into the host's striatal parenchyma regardless of the existence of long-range anatomical connections.