Anatomical and functional consequences of grafting mesencephalic neurons into a peripheral nerve "bridge" connected...

Adult rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway were tested for amphetamine-induced rotational asymmetry. In animals with functional deficits a fetal mesencephalic transplant was placed intracranially over the superior colliculus within the caudal end of a 2- to 3-cm-long heterologous sciatic nerve segment laid longitudinally on the skull. Two months later the rostral tip of the peripheral nerve graft was cut and inserted through a burr-hole into the denervated striatum. Animals were tested monthly for 5 months for rotational asymmetry and selected rats were sacrificed for histochemical examination. It was shown that the use of a peripheral nerve segment as a bridge between a distant neuronal transplant and a selected region of the adult host brain resulted in the growth of monoaminergic axons into the denervated striatum from the extracerebrally located grafted neurons. The nerve bridge was cut extracranially in rats whose rotational asymmetry had decreased towards normal levels to determine if this behaviour was dependent on axons reaching the striatum through the graft. Each of these animals exhibited an increase in rotational asymmetry one and three weeks after the transection of the nerve. These anatomical and functional observations suggest that the decrease in rotational asymmetry observed in these animals is related to the growth of long axons from the implanted mesencephalic neurons into the denervated host's striatum which traversed the entire peripheral nerve segment.