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Cellular and molecular requirements for growth of sensory axons into the spinal cord

Objective

To achieve restoration of function after injury to spinal cord sensory systems by:
transplantation of embryonic sensory nerve (ganglion) cells,
local administration of growth factors, and/or antibodies which block growth-inhibitory factors,
transplantation of supporting cells which promote nerve fibre growth.

The ultimate objective of the proposal is to achieve functionally useful regeneration of injured nerve fibres in the central nervous system. This is one of the main priorities of neuroscience research, considering the frequency of these conditions and their devastating consequences of brain and spinal cord injuries in terms of suffering for the affected human beings as well as the economic demands for the society. The teams involved in this proposal will focus their expertise on a system, which offers particular advantages for the study of nerve fibre regeneration, its failure in the central- nervous system and how this failure may be overcome. This system is the sensory fibres originating from sensory ganglia outside the spinal cord, and coursing within the dorsal roots into the spinal cord. During this course they traverse the interface between the peripheral and central nervous system, a boundary which is a well established "barrier" to nerve fibre growth.

Previous research by the teams have identified new possibilities to make nerve fibres grow through this "barrier". One is transplantation of embryonic human sensory ganglia to the cavity of extirpated ganglia of adult rat. Fibres from the embryonic ganglia grow into the host dorsal root and enter the host spinal cord. The other is to destroy the "barrier" tissue and implant a collection of non-neuronal cells at this site. These cells derive from the olfactory system, and have been shown to support nerve fibre growth in the spinal cord. Other previous studies by the teams make it likely that these models of axon regeneration into the spinal cord can be markedly improved by the use of specific growth factors, so-called neurotrophins, as well as by the use of antibodies, which can block some of the molecules underlying the inhibition to nerve fibre growth in the mature central nervous system. The teams have developed the knowledge and technology to implement these possibilities in the system described.

Finally, given the fact that the glial interface in the dorsal root has such a powerful negative influence on growth of mature nerve fibres, the team will use their special knowledge to unravel the structural and molecular mechanisms underlying this growth inhibition. Through the collaborative actions, the studies undertaken by the teams are likely to generate information, which will be useful for the development of new treatment strategies, particularly for traumatic disorders of the central nervous system, such as sensory root avulsion as well as spinal cord and brain damage. The development of these new therapeutic strategies will make new targets available for the pharmaceutical and biotechnological industry in Europe.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Uppsala University
Address
3,Biomedicum, Husargatan
751 23 Uppsala
Sweden

Participants (4)

Consejo Superior de Investigaciones Cientificas
Spain
Address
37,Avenida Doctor Arce
28002 Madrid
National University of Ireland, Cork
Ireland
Address

30 Cork
Queen Mary and Westfield College
United Kingdom
Address
Mile End Road
E1 4NS London
United Medical and Dental Schools of Guy's and St Thomas's Hospitals
United Kingdom
Address
Lambeth Palace Road
SE1 7EH London