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Volume 16, Number 21, Issue of November 1, 1996 pp. 6965-6974
Copyright ©1996 Society for Neuroscience

Constructing a New Nigrostriatal Pathway in the Parkinsonian Model with Bridged Neural Transplantation in Substantia Nigra

Received May 14, 1996; revised Aug. 2, 1996; accepted Aug. 12, 1996.

Feng C. Zhou¹, Yung H. Chiang¹, and Yun Wang²

¹ Department of Anatomy and Medical Neurobiology Program, Indiana University School of Medicine, Indianapolis, Indiana 46202, and ² Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan

The physical repair and restoration of a completely damaged pathway in the brain has not been achieved previously. In a previous study, using excitatory amino acid bridging and fetal neural transplantation, we demonstrated that a bridged mesencephalic transplant in the substantia nigra generated an artificial nerve pathway that reinnervated the striatum of 6-hydroxydopamine (6-OHDA)-lesioned rats. In the current study, we report that a bridged mesencephalic transplant can anatomically, neurochemically, and functionally reinstate the 6-OHDA-eradicated nigro-striatal pathway. An excitatory amino acid, kainic acid, laid down in a track during the transplant generated a trophic environment that effectively guided the robust growth of transplanted neuronal fibers in a bundle to innervate the distal striatum. Growth occurred at the remarkable speed of ~200 µm/d. Two separate and distinct types of dopamine (DA) innervation from the transplant have been achieved for the first time: (1) DA innervation of the striatum, and (2) DA innervation of the pars reticularis of the substantia nigra. In addition, neuronal tracing revealed that reciprocal connections were achieved. The grafted DA neurons in the SNr innervated the host's striatum, whereas the host's striatal neurons, in turn, innervated the graft within 3-8 weeks. Electrochemical volt- ammetry recording revealed the restoration of DA release and clearance in a broad striatal area associated with the DA reinnervation. Furthermore, the amphetamine-induced rotation was attenuated, which indicates that the artificial pathways were motor functional. This study provides additional evidences that our bridged transplantation technique is a potential means for the repair of a completely damaged neuronal pathway.

Key words: excitatory amino acid; neural transplant; dopamine; pathway repair; voltammetry; HRP/immunocytochemistry double staining; rotational behavior

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