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Volume 16, Number 22, Issue of November 15, 1996 pp. 7216-7227
Copyright ©1996 Society for Neuroscience

Reconstruction of the Nigrostriatal Pathway by Simultaneous Intrastriatal and Intranigral Dopaminergic Transplants

Received May 6, 1996; revised Aug. 27, 1996; accepted Aug. 29, 1996.

Ivar Mendez, Damaso Sadi, and Murray Hong

Neural Transplantation Laboratory, Departments of Surgery (Division of Neurosurgery), and Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7

The main strategy in experimental and clinical neural transplantation in Parkinson's disease has been to place fetal nigral grafts not in their ontogenic site (substantia nigra) but in their target area (striatum). The reason for this ectopic placement is the apparent inability of nigral grafts placed in the ventral mesencephalon (VM) of the adult host to grow axons for long distances that are capable of reaching the ipsilateral striatum and thus restoring the nigrostriatal pathway.

The present study demonstrates for the first time that simultaneous dopaminergic transplants (double grafts) placed in the substantia nigra and ipsilateral striatum of rats bearing unilateral 6-hydroxydopamine lesions reconstruct the dopaminergic nigrostriatal pathway in the adult rat brain. Numerous tyrosine hydroxylase-immunoreactive axons were observed arising from the intranigral graft and growing rostrally along the internal capsule and medial forebrain bundle to reinnervate the ipsilateral striatum, which also had received a dopaminergic graft. These double grafts achieved not only greater striatal reinnervation than the standard intrastriatal graft but also a faster and more complete rotational recovery to amphetamine challenge 6 weeks after transplantation.

These results suggest strongly that embryonic nigral transplants implanted in the striatum are capable of promoting growth and providing guidance to axons arising from a dopaminergic graft placed homotopically in the VM, resulting in restoration of the dopaminergic nigrostriatal projection. Reconstruction of the nigrostriatal pathway by double grafts may not only achieve substantial striatal reinnervation but may also contribute to the reestablishment of dopaminergic regulation of the nigrostriatal circuitry.

Key words: double grafts; Parkinson's disease; neural transplantation; dopamine; nigrostriatal pathway; fetal transplants

This article has been cited by other articles:

				D. E. Redmond Jr. Book Review: Cellular Replacement Therapy for Parkinson's Disease--Where We Are Today? Neuroscientist, October 1, 2002; 8(5): 457 - 488. [Abstract] [PDF]

				K. Mukhida, K. A. Baker, D. Sadi, and I. Mendez Enhancement of Sensorimotor Behavioral Recovery in Hemiparkinsonian Rats with Intrastriatal, Intranigral, and Intrasubthalamic Nucleus Dopaminergic Transplants J. Neurosci., May 15, 2001; 21(10): 3521 - 3530. [Abstract] [Full Text] [PDF]

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