- Decorin as an anti-scarring agent after spinal cord injury (Logan, Ahmed)
Spinal cord injury induces pathological changes such as scarring that impede recovery of function and can also form the focus of post-injury epileptic attacks. We are analysing drugs that will act as antifibrotic therapies and suppress acute post-injury scar formation in the CNS. One such drug is decorin, a small leucine-rich antagonist of TGF-β that attenuates TGF-β activation and signalling through their receptors. We aim to evaluate the therapeutic potential of decorin to inhibit scarring in the spinal cord and brain.
- Cavitation after spinal cord injury (Ahmed, Logan)
In most mammals, progressive tissue necrosis occurs after SCI leading to the formation of fluid filled cavities and is potentially a life threatening condition in humans. Several lines of evidence suggest that promotion of angiogenesis improved wound healing and reduces cavitation after SCI. We are using state-of-the-art gene detection studies, including microarray and deep sequencing technologies to identify genes involved in angiogenesis/wound healing with the aim of reducing cavitation after spinal cord injury.
- Definition of genes that contribute to axon regeneration after SCI (Ahmed, Logan)
In contrast to adult neurons of the peripheral nervous system, damaged CNS axons do not spontaneously regenerate due to limitations that include; neuronal loss by apoptosis, reduced intrinsic growth capacity of neurons and the presence of a non-permissive environment in the injured adult CNS preventing axon growth. There are three major inhibitory components of CNS myelin, Nogo-66, myelin associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp) that bind a common receptor, the Nogo-66 receptor (NgR1) and associate with the signal transducing receptor, p75 and its co-receptor LINGO-1, signalling inhibition of CNS axon growth through a RhoGTP-mediated pathway. In addition, TAJ/TROY was also identified as a surrogate receptor for p75 since not all neuronal populations that responded to myelin contained p75.
Due to the variety of different molecules involved in blocking axon regeneration after injury, understanding how they function and interact is pertinent to be able to devise ways to overcome these molecules effectively. We are therefore defining the function of genes and assessing their contribution to CNS axon regeneration with a view to devising better therapeutic molecules to enhance axon regeneration.