Spinal Cord Injury Research

spinal-cord-i Injury Research BannerOverview

Spinal cord injury (SCI) affects more than 2.5 million people worldwide, with approximately 130,000 new cases each year. SCI can lead to devastating long-term effects and potential therapies only help reduce pain for affected individuals. Trauma to the brain or spinal cord triggers a complex and rapidly evolving interplay of inflammatory, dysmetabolic, degenerative and compensatory mechanisms that determine the fate of the injured tissue. The understanding of these cellular responses and their interconnection with genetic, systemic and environmental factors is key the development of neuroprotective treatments.

Our research

The SCI group studies both acute and chronic changes that occur after SCI with the aim of identifying therapeutic compounds to promote recovery of lost function. Our lab uses in vivo and in vitro models that have been developed to mimic the pathophysiological changes seen in SCI patients. We have particular interest in how SCI causes spinal cord cavities, understanding the molecular mechanisms that underpin CNS regenerative failure, the development of antifibrotic agents and identification of new genes involved in promoting CNS axon regeneration. Our research focuses on novel technologies to detect early signatures of damage before this becomes irreversible (e.g. metabolic impairment, spinal cord swelling, neuroinflammation, cavitation etc.), thus allowing the development of targeted intervention and personalised treatments. 

Our research is cross-disciplinary and links in areas such as Medicine, Psychology, Imaging, Sports and Exercise Sciences, Bioengineering, Chemistry and Computing Sciences.

Current Projects 

  • 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.

Recent Publications

Surey S, Berry M, Logan A, Bicknell R and Ahmed Z (2014) Differential cavitation, angiogenesis and wound-healing responses in inured mouse and rat spinal cords. Neuroscience 275:62-80

Ahmed Z, Bansal D, Tizzard K, Surey S, Esmaeili M, Gonzalez AM, Berry M and Logan A (2014) Decorin blocks scarring and cystic cavitation in acute and induces scar dissolution in chronic spinal cord wounds. Neurobiol Dis 64:163-76

Ahmed Z, Douglas MR, John G, Berry M and Logan A (2013) AMIGO3 is an NgR1/p75 co-receptor signalling axon growth inhibition in the acute phase of adult central nervous system injury. PLoS One 8(4):e61878

Vigneswara V, Berry M, Logan A and Ahmed Z (2013) Caspase-2 is upregulated after sciatic nerve transection and its inhibition protects dorsal root ganglion neurons from apoptosis after serum withdrawal. PLoS One 8: e57861.

Jacques SJ, Ahmed Z, Forbes A, Douglas MR, Vigneswara V, Berry M and Logan A (2012) AAV8(gfp) preferentially targets large diameter dorsal root ganglion neurones after both intra-dorsal root ganglion and intrathecal injection. Mol Cell Neurosci 49(4):464-74

Ahmed Z, Douglas MR, Read ML, Berry M and Logan A (2011) Citron kinase regulates axon growth through a pathway that converges on cofilin downstream of RhoA. Neurobiol Dis 41(2):421-9

Lagord C, Berry M and Logan A (2002) Expression of TGFbeta2 but not TGFbeta1 correlates with the deposition of scar tissue in the leioned spinal cord. Mol Cell Neurosci 20(1):69-92

Research Team

Principal Investigators
Dr Zubair Ahmed - Senior Lecturer in Neuroscience, Institute of Inflammation and Ageing
Professor Ann Logan - Professor of Molecular Neuroscience, Institute of Inflammation and Ageing

Honorary Staff 
Professor Martin Berry -  - Professor of NeuroAnatomy (Emeritus), Institute of Inflammation and Ageing

Internal Collaborators
Dr Kevin Whitehead - Lecturer in Neuropharmacology, Institute of Clinical Sciences
Professor Liam Grover - Professor in Biomaterials Science, School of Chemical Engineering
Professor Roy Bicknell - Professor of Functional Genomics, Institute of Cardiovascular Sciences