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Back to basics: reactivating fundamental processes that repair the developing brain to rebuild neuronal circuits following injury

Final Activity Report Summary - RMS-BDNFCNSRepair (Back to basics ? reactivating fundamental processes that repair the developing brain to rebuild neuronal circuits following injury.)

The overall objective of the proposal was to increase our understanding on how to reproduce within the mature brain the natural repair that follows injury to the immature nervous system, therefore improving recovery from brain injury. The project used our well-established model of nervous system injury, namely the rat olivocerebellar path, to investigate the mechanisms by which one growth factor, called BDNF, recreated spontaneous developmental olivary climbing fibre axon reinnervation onto mature cerebellar Purkinje cells.

During the project we identified three factors that regulated gene expression, i.e. transcription factors, and two groups of molecules that controlled cell to cell interactions, i.e. extracellular matrix molecules, whose expression changed during both spontaneous and BDNF-induced olivocerebellar reinnervation. In order to facilitate this investigation we optimised a simpler model of olivocerebellar reinnervation, grown in culture. The importance of this technical advancement was that it allowed us to separately examine the relative contribution of the newly growing connections versus the target Purkinje cells on the success or failure of neural circuit repair.

We also began testing the role of the two groups of extracellular molecules in BDNF-induced olivocerebellar reinnervation. Even though we examined one in the host laboratory, in order to study the second, which was a group of growth-inhibitory molecules called ephrins, we used transgenic mice which did not express these molecules. In addition to providing a means of testing the role of these molecules in post-injury repair, obtaining these mice established a beneficial ongoing international collaboration and increased awareness of European research in Australia.