Repair of the damaged brain. The Alfred Meyer Memorial Lecture 1998

Over the last decade, neural transplantation has progressed from being an e xperimental technique for studying regeneration and plasticity in the brain to clinical trials of reconstructive surgery in human neurodegenerative di sease. Whereas clear evidence is only available at present for the viabilit y of this technique in Parkinson's disease, applications to several other d iseases, including Huntington's disease, multiple sclerosis, spinal cord in jury, and chronic pain are currently under active consideration. It is clea r that the techniques of transplantation can be functionally viable under c ertain well-defined biological circumstances, but significant problems rema in in the availability of suitable donor tissues and defining the optimal c onditions for reliable survival of the implanted cells. If we are to obtain improved reliability of the present techniques or identify suitable altern atives, we need a better understanding of the conditions for the survival a nd integration of grafts into the host brain, and the mechanisms by which t hey influence host function. In this review I consider the nature of the st ructural reconstruction required to achieve repair in animal models of Park inson's and Huntington's diseases, contrasting the replacement of deficient neurochemicals within the striatum in the former case, and the need for re construction of input and output connections of the striatal circuitry in t he latter.