Simultaneous intrastriatal and intranigral grafting (double grafts) in therat model of Parkinson's disease

Experimental and clinical studies of neural transplantation in Parkinson's disease have focused on the placement of fetal dopaminergic grafts not in t heir ontogenic site (substantia nigra) but in the main nigral target area ( striatum). The reason for this is the apparent inability of intranigral nig ral grafts to extend axons for long distances reinnervating the ipsilateral striatum. This review presents previous work by our laboratory [I. Mendez, M. Hong, Reconstruction of the striato-nigro-striatal circuitry by simulta neous double dopaminergic grafts: a tracer study using fluorogold and horse radish peroxidase, Brain Res. 778 (1997) 194-205; I. Mendez, D. Sadi, M. I- long., Reconstruction of the nigrostriatal pathway by simultaneous intrastr iatal and intranigral dopaminergic transplants, J. Neurosci. 16 (1996) 7216 -7227] using a new transplantation strategy aimed at restoring dopaminergic innervation of the nigra and striatum by simultaneous dopaminergic transpl ants placed in the substantia nigra and ipsilateral striatum (double grafts ) in the B-hydroxydopamine lesioned adult rat brain. These double grafts ac hieve not only greater striatal reinnervation than the standard intrastriat al grafts but also produce a faster and more complete behavioural recovery six weeks after transplantation. Injection of the retrograde tracer fluorog old into the striatum and nigra resulted in fluorescent labeled cells withi n the intranigral graft and the intrastriatal graft and surrounding striatu m, respectively suggesting that these double grafts promote at least partia l reconstruction of the nigrostriatal dopaminergic pathway, This double gra ft strategy may have potential implications in clinical neural transplantat ion for Parkinson's disease. (C) 2000 Elsevier Science B.V. All rights rese rved.