Effect of intracerebroventricular infusion of epidermal growth factor in rats hemitransected in the nigro-striatal pathway.

The most recent attempt at surgical treatment of Parkinson's disease is represented by implant of dopaminergic tissue in the striate nuclei. Growth factors have been associated to the neural implants in order to favor successful grafting and functional survival. Among diverse growth factors Epidermal Growth Factor (EGF) is active in vitro on axonal regeneration of dopaminergic cells of the substantia nigra. Our research group has recently assessed the effect of a 35-day delayed intracerebroventricular infusion of EGF on the survival and function of the dopaminergic neurons in rats made hemiparkinsonian by unilateral mechanical transection of rat nigrostriatal pathway. EGF infusion resulted in a two-fold increase in the number of surviving tyrosine hydroxylase (TH)-positive substantia nigra neurons and a significant increase in ipsilateral striatal TH-positive fiber staining compared to controls. In addition there was a persistent enhancement of behavioral recovery, as indicated by a reduction in amphetamine-induced rotations. In the present study EGF is tested at a lower dosage starting administration at the time of lesion. Effects have been assessed by the available functional and biochemical methods. Results confirm that neurotrophic effect of EGF on dopaminergic neurons in the nigro-striatal pathways follow early administration also at low dosage.