Reconstructing the neural circuits in Parkinson’s, using biodegradablepolymer bridges or striatal co-grafts to encourage neural outgrowth from transplantedtissue

In Parkinson's disease, the neurocircuitry, called the nigrostriatal pathway, is lost. This pathway links the substantia nigra to the striatum. In neural tissue transplants for Parkinson's disease patients, new neural tissue from the fetal substantia nigra is placed into the striatum. The clinical outcome for this procedure has been variable, possibly because it by-passes the nigrostriatal pathway. It has been suggested that the new neural tissue does not know how to behave without input from the substantia nigra and this may be the cause of clinical variation. We are proposing two methods with which we will try rebuild the nigrostriatal pathway in a pre-clinical model of Parkinson's disease. In both methods, new neural tissue from the rat fetal substantia nigra will be transplanted into the parkinsonian adult rat substantia nigra rather than the striatum. In the first method, the new tissue will then be bridged to the striatum with additional fetal neural tissue co-grafts placed along a direct route between the substantia nigra and the striatum. It is hypothesized that the co-grafts will attract neural fiber outgrowth from the new neural tissue in the substantia nigra. As the new fibers grow to reach consecutive co-grafts and eventually reach the striatum, they should function as a new neurocircuit between the substantia nigra and striatum. In the second method, a bio-absorbable polymer will be used to bridge the new tissue to the striatum. Some studies suggest that neural fiber outgrowth is better when the fibers have a physical surface on which to grow. It is hoped that neural fiber outgrowth from the new tissue will use the polymer as a guide with which they will follow to the striatum. The advantage of the polymer over the neural tissue co-grafts is that the polymer is bio-absorbable, meaning that while the neural fibers are reaching their destination, the polymer is being reabsorbed, eventually leaving only a pure neurocircuit between the substanti nigra and striatum. The insight gained by studying the reconstruction of the nigrostriatal pathway for Parkinson's disease carries potential for other neurodegenerative disorders including Huntington's disease, stroke, and spinal cord research.