Objective Recent studies have indicated that combinatorial treatments that target multiple mechanisms are necessary to address the limited regenerative capacity in the adult nervous system. We have shown that chemotropic guidance by growth factor gradients, activation of cell-intrinsic regenerative programs and suitable cellular bridges at a lesion site allow for axons to extend across a lesion site in the injured spinal cord. Further, regenerated axons form ultrastructurally identified synapses with appropriate target neurons. However, several challenges that limit the relevance of current approaches remain: Regenerating axons only extend for limited distances beyond the lesion site and axons are not functional possibly due to an insufficient number of synapses or a lack of myelination.The proposed experiments will address these limitations in 3 specific aims. We will examine spatially and temporally controlled expression of neurotrophic factors (NT-3) to enhance the distance of regeneration and target reinnervation by ascending sensory axons after adult spinal cord injury. We will further define the requirements for persistent target innervation using transient neurotrophin expression and we will examine whether localized degradation of inhibitory extracellular matrix will enhance synapse formation with target neurons. Finally, we will determine whether Schwann cell and oligodendrocyte precursor cell grafts can re-myelinate regenerating axons and augment functional connectivity and electrophysiological recovery of regenerated axons. Fields of science natural sciencesbiological sciencesneurobiology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Call for proposal FP7-PEOPLE-2010-RG See other projects for this call Funding Scheme MC-IRG - International Re-integration Grants (IRG) Coordinator UNIVERSITATSKLINIKUM HEIDELBERG EU contribution € 100 000,00 Address Im neuenheimer feld 672 69120 Heidelberg Germany See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Higher or Secondary Education Establishments Administrative Contact Thorsten Brietz (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data