The internationally recognised Centre for Neuroscience and Trauma has about 65 academic staff, research assistants and PhD students, with research interests mainly in the fields of neural injury and repair. The Centre was established in June 2003 and encompasses the former academic departments of Neuroscience, Neurosurgery, Neurology and Neuropathology. The Centre thus comprises an interdisciplinary group of clinical and non-clinical scientists, with a particular focus on translational neuroscience. Staff have long-standing interests in peripheral neuropathies, spinal cord injuries and neurodegeneration and this work was flagged in the 2001 RAE. The Centre has greatly expanded since 2001 but its research remains focused on three interrelated topics, namely (1) the role of primary sensory neurons and effects of peripheral nerve injury, (2) traumatic and degenerative disorders of the central nervous system (CNS), and (3) molecular mechanisms of development and tumorigenesis. Research is currently supported by project and programme grants from BBSRC, MRC, EU Framework 6, International Spinal Research Trust (ISRT), the National MS Society, Corporate Action Trust, the Research Advisory Board of St Bartholomew's and The Royal London Charitable Foundation (RAB), and Cancer Research UK . The Centre also has substantial funding from industry (Stryker UK , Serono, Biogen-Idec) and from biomedical seed funds (Heptagon Fund and Kinetique). The current Head of Centre is Prof Gavin Giovannoni.

 

Primary sensory neurons

Work focuses on the fundamental role played by neurotrophic factors and cytokines in regulating adult dorsal root ganglion (DRG) cells, the importance of such factors in pain states, and strategies to promote peripheral nerve regeneration. Prof Priestley's group was the first to establish that nociceptive DRG neurons comprise two main subpopulations which differ in their growth factor dependence and expression of neuropeptides. This work is continuing, with further study of the properties of nociceptive DRG neurons, their expression of key transduction molecules and ion channels, and their response to injury. Work by Prof Peter Richardson was key to identifying the "conditioning response", whereby the regenerative response of somatosensory neurons is augmented by a prior injury. Ongoing studies focus on the role of the JAK/STAT signalling pathway in this response, and the relationships between cytokine signalling and cAMP pathways. Prof Priestley's group has shown that novel silks developed by Oxford Biomaterials can support neural regeneration. This work is now funded by a grant from Kinetique, awarded to establish a start-up company (Neurotex) and develop silk-based conduits for peripheral nerve repair.

 

Traumatic and Degenerative CNS Injury

The centre has an established reputation for work on degenerative disorders including motoneurone disease (Prof Jo Martin) and traumatic injury to the spinal cord (Prof John Priestley). This has recently been further strengthened with the establishment of a neuroimmunology group (Prof David Baker, Prof Gavin Giovannoni) with a focus on multiple sclerosis (MS) and basal ganglia autoimmune diseases. Research ranges from cell and molecular studies in vitro , through in vivo rodent models, to clinical trials and this translational focus is facilitated by the presence of a full-time trials coordinator. Ongoing studies include root avulsion injury, molecular strategies to promote regeneration, and cannabinoid signaling, and hence link closely with the peripheral nerve work of the Centre. Studies on spinal cord injury include the use of fibronectin implants to fill cystic cavities and support axonal regeneration (Prof Priestley), strategies to promote regeneration after ventral root avulsion injury (Dr Peter Shortland), and use of omega-3 polyunsaturated fatty acids (PUFAs) as neuroprotective agents (Dr Adina Michael-Titus, Prof Priestley). A phase 1 safety study of PUFA treatment in spinal cord injury is planned, and a pilot clinical study in Alzheimer's disease is underway (Dr Michael-Titus). Key recent achievements related to motor neuron disease include the linkage of axonal transport defects to motor neuron loss in dynein mutations (Prof Martin) and gene array analysis of common mechanisms underlying motor neuron disease and cell death following spinal cord injury (Dr Andrea Malaspina). The neuroimmunology group lead the field in studies of endocannabinoids in MS and the possible therapeutic use of cannabinoids in MS (Prof Baker, Prof Giovannoni). They have also highlighted the role of anti basal ganglia autoantibodies in PANDAS and in other movement disorders, and are developing novel treatments for MS based on induction of immune tolerance.

 

Development and neuro-oncology

The molecular events that determine gene transcription and cellular differentiation are being studied, both in normal development and in tumour formation. Major themes currently under investigation include the role of chromatin and nuclear architecture in transcription (Prof Denise Sheer) , genetic defects associated with glioblastoma multiforme (Prof Sheer), the molecular events that control cerebellar granule cell development and their contribution to the pathogenesis of medulloblastoma (Prof Silvia Marino), and the role of neural stem cells and self renewal mechanisms in the ontogenesis of brain tumours (Prof Marino). The latter studies provide a strong link with stem cell work in other ICMS research centres.

Figure legend: Immunoflurescence micrograph showing axonal growth on a fibronectin-based biomaterial designed to bridge an area of spinal cord damage. Axons (blue, indicated by arrow heads) grow on an extracellular matrix component (laminin, green) which has been deposited by Schwann cells (red, indicated by arrows).