BRAIN REPAIR - LESSONS FROM DEVELOPMENTAL BIOLOGY

The failure of the adult human central nervous system (CNS) to repair following injury has significant clinical consequences. Lesions caused by trauma, vascular defects or chronic inflammation can result in lon g-standing damage and considerable functional impairment for which the re are no effective remedies at present. A major goal of neuroscience research is, therefore, to devise strategies for effective repair foll owing CNS damage. One of the most important of these strategies is tra nsplantation. The goal of this work is to transplant cells into the da maged brain either to replace tissue directly or to stimulate the abil ity of the CNS to repair itself. Promising initial results have emerge d with transplantation for the very focal defect of Parkinson's diseas e, using fetal dopaminergic neurons placed directly into the denervate d striatum. However, to repair widespread lesions it seems likely that the transplanted cells will have to be altered so as to enhance their potential to initiate or facilitate repair. In this review, we emphas ize the importance of understanding the developmental biology of the s ystem in question before attempting manipulation of cells prior to tra nsplantation. This point of view stems from observations that mechanis ms used during development are often reexpressed in those systems that repair effectively. It follows that manipulating cells to be transpla nted so as to re-express molecules present in development may enhance repair in those areas where repair is normally minimal.