Neural Injury Research Unit

Research Current Projects Staff and Students Collaborations Research Grants Publications

Members of the Neural Injury Research Unit

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Research

Neuroscience involves some of the most exciting challenges in biology today. Understanding how the nervous system functions and how it reacts to injury is essential if we are to help conditions like paraplegia. Our lab studies cellular and behavioural changes after injury, in both animals and humans, to tackle clinically relevant problems such as spinal cord injury.

The Neural Injury Research Unit comprises academic and research staff, postgraduate and honours students who are working on projects such as those listed below.

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Current Research Projects

Repair of injured spinal cord

Spinal cord injury continues to be a major cause of disability, particularly amongst young people involved in road related trauma, falls and sports injuries. Each year in Australia, approximately 300 people sustain a severe traumatic spinal injury. Particularly distressing is the fact that the typical spinal injury patient is young and otherwise healthy. Many are left wheelchair-bound, with permanent disabilities and constant dependence for the rest of their lives.

There has been much excitement recently about the possibility of repairing the damaged spinal cord following injury. Several research labs around the world are reporting that cellular therapies can lead to repair after transection of the spinal cord in adult animals. These studies have raised hopes that treatment for paraplegia may eventually be possible. Our group has shown that a special type of glial cell, the olfactory ensheathing cell (OEC, Fig 1), can promote recovery of movement in rats (Fig 2) and support regeneration of serotonergic connections. Human trials are underway in Brisbane with the transplanting of OECs into the spinal cords of paraplegic patients.



Further, under a Program Grant from the NSW Government, our lab is comparing three types of stem cells: embryonic, adult bone marrow and adult neural stem cells as possible sources of spinal cord repair.

Treadmill training is another treatment that our lab has trialled in spinally injured rats with positive results. Our studies have found that passive movement of the hind-limbs of injured animals can improve the locomotor ability of the animals.

Cardiovascular function following spinal cord injury

Besides an inability to walk, spinal patients have problems with bladder, bowel and sexual function, as well as cardiovascular and temperature regulation. For most paraplegics, these autonomic problems are of more concern than the inability to walk. Our group is using state-of-the-art telemetry to evaluate the potential of OEC’s to reduce the cardiovascular problems suffered by quadriplegics.

So far our cardiovascular studies have been promising, with OEC’s improving the cardiovascular responses of spinalised rats (see Fig 3).

Temperature regulation following spinal cord injury

High spinal cord injury also results in loss of temperature regulation. Infrared imaging allows comparison of intact (Fig 4A) and spinalised rats (Fig 4B) and the technique is useful for testing various treatments after injury. Thermal imaging is also used to study challenges such as exercise, cold and heat stress.

Neurotrophin supplementation in the injured spinal cord

After an injury, the adult spinal cord fails to regenerate and damage at cervical levels are particularly devastating as they may result in quadriplegia. However, there is now evidence that delivery of neurotrophins to the injured spinal cord can elicit axonal growth and regenerative sprouting. The focus of Renee Morris’ research is to use adenoviral vectors to up-regulate levels of neurotrophins into spinal cord motor neurones in an animal model of partial spinal cord transection. It is hypothesised that this gene therapy scenario will assist the recovery of fine motor control of the hand as measured with diverse behavioural tasks.

Reaching following nerve root injury

Another common injury in people is damage to the nerve roots which control the arms, known as brachial plexus avulsion. Again we are using rats to test possible repair strategies. Following dorsal root injury, failed forepaw reaching is seen on many occasions, indicated by rats missing the pellets due to dropping, inaccurate aiming and phantom grasps. We will now trial OECs to improve this arm and hand function.


Pain following nerve root injury

Pain perception can be impaired or aggravated following spinal cord injury, leading to conditions such as chronic pain, allodynia and hyperalgesia. Methods for testing pain perception in spinalised animals include the use of Von frey hairs for innoxious tactile sensation and radiant heat stimulation to induce analgesia. We have developed an animal model to test cellular repair for pain after injury. Preliminary results have shown that injury to 2 nerve roots produces greater thermal hyperalgesia (indicated by significantly decreased withdrawal latency) than injury to 4 roots (Fig 6).

Human functional assessment

The NSW Program grant is also developing improved assessment techniques for monitoring sensory and autonomic function and pain perception for spinal patients. The refined assessments are essential prior to any clinical trials of potential cellular treatments, so that progress can be accurately monitored. Electrical perceptual threshold (EPT), sympathetic skin response (SSR) and skin blood flow are being compared after complete and incomplete spinal injuries.

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Staff and Students

Staff

• Dr Cathy Gorrie, Research Officer
• Dr Renee Morris, Research Fellow
• Dr Frank Cloutier, Research Associate
• Angela Laird, Research Assistant
• Jenny Lauschke, Research Assistant
• Linda Larsen, Technical Officer

Students

• Dr Tomas Kalincik, PhD Student
• Ann Wu, PhD Student
• Jingyi Cao, AMS Student from Melbourne University
• Phillip Yang, ILP Student under Cathy Gorrie

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Collaborations

Cardiovascular Function

• Associate Professor Pascal Carrive – Department of Anatomy, University of New South Wales, Sydney
• Dr Angela Finch – Department of Pharmacology, University of New South Wales, Sydney

Repair Strategies

• Professor Alan McKay Sim - Biomolecular and Biomedical Science, Griffith University, Brisbane
• Professor Ian Hayward - Biomolecular and Biomedical Science, Griffith University, Brisbane
• Dr Colm Cahill - Biomolecular and Biomedical Science, Griffith University, Brisbane
• Professor Colin Green – Department of Ophthalmology, Auckland University, Auckland, New Zealand
• Professor Louise Nicholson - Department of Anatomy with Radiology, Auckland University, Auckland, New Zealand
• Dr Simon O'Carroll – Department of Anatomy with Radiology, Auckland University, Auckland, New Zealand
• Professor Bernie Tuch – Diabetes Transplant Unit, Prince of Wales Hospital, Sydney

Behavioural Trials

• Professor Lesley Rogers – Centre for Neuroscience and Animal Behaviour, University of New England, Armidale Australia
• Professor Ian Whishaw, FRSC – Canadian Centre for Behavioural Neuroscience, Lethbridge University, Alberta, Canada

Clinical Assessments

• Dr Grace Leong – Senior Staff Specialist- Royal North Shore Hospital, Sydney
• Dr Susan Rutkowski – Spinal Cord Injury Medicine and Research Unit, Royal North Shore Hospital, Sydney

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Research Grants

• NSW MSMR Program grant 2005-2008
• International Spinal Research Trust 2006-2008
• Christopher and Dana Reeve Foundation (Renee Morris- Chief Investigator)
• Medical Faculty Early Career Research Grant (Cathy Gorrie- Chief Investigator)

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Recent Publications (2002 - present)

Chapters in Books

• Ashwell KWS and Waite PME (2004) Development of the peripheral nervous system. In Human Nervous System, 2nd edn, ed Paxinos G and Mai JK, Elsevier, pp95-110.
• Waite PME and Ashwell KWS (2004) Trigeminal Sensory System. In Human Nervous System, 2nd edn, ed Paxinos G and Mai JK,Elsevier, pp 225-256.
• Waite PME and Ashwell KWS (2004) Trigeminal Sensory System. In Rat Nervous System, 3rd edn, ed Paxinos G, Elsevier, pp 817-851.

Journal Articles (since 2002)

• Lu J, Feron F Mackay-Sim A and Waite PME (2002) Olfactory ensheathing cells promote locomotor recovery after delayed transplantation into transected spinal cord. Brain 125: 14-21.
• Zhu XO, de Permentier PJ and Waite PME (2002) Cholinergic depletion by IgG192-saporin retards development of rat barrel cortex. Dev. Brain Res (in press).
• Mark RF, Flett DL, Marotte LR and Waite PME (2002) Developmental onset of functional activity in the wallaby whisker cortex in response to stimulation of the infraorbital nerve. Somato Motor Res. (in press).
• Gorrie CA, Oakes S, Duflou J, Blumbergs P, and Waite PME (2002) Axonal injury in children following motor vehicle cashes: extent, distribution and size of axonal swellings using B-APP immunohistochemistry. J Neurotrauma 10: 1171 - 1182.
• Ho SM, Waite PME (2002) Effect of different anaesthetics on the paired-pulse depression of the H-reflex in adult rat. Exp. Neurol. 177, 494 - 502.
• Gorrie CA, Duflou J, Rodriguez M, Sachdev P and Waite PME (2003) Older pedestrian fatalities - does neurodegeneration play a role? Proc. Road Safety Research Policing and Education Conference (invited peer reviewed paper).
• Fiford RJ, Bilson, LE, Waite PME and Lu J (2004) A vertebral dislocation model of spinal cord injury in rats. J. Neurotrauma 21: 451-458.
• Choi EA, Leman S, Vianna DML, Waite PME and Carrive P (2005) Expression of cardiovascular and behavioural components of conditioned fear to context in T4 spinally transected rats. Autonomic Neurosci. 120: 26-34
• Woodhouse A, Vincent AJ, Kozel MA, Chung RS, Waite PME, Vickers JC, West AK and Chuah MI (2005) Spinal cord tissue affects ensheathing cell proliferation and apoptosis. NeuroReport 16: 737-740.
• Gorrie CA, Rodriguez, ML, Duflou J, Sachdev PS and Waite PME (2006) Increased neurofibrillary tangles in the brains of elderly pedestrians killed in traffic accidents. Dementia Cog Geriat Dis. 22: 20-6.
• Waite PME, Gorrie CA, Herath NP, Marotte LR. (2006) Whisker maps in marsupials: nerve lesions and critical periods. Anat Rec A Discov Mol Cell Evol Biol. 288:174-81.
• Duflou FA, Nickols G, Waite PME, Griffiths R and Sage M (2006) Artefactual contraction band necrosis of the myocardium in fatal air crashes. Aviat. Space Environ. Med. 77: 944-949.
• Deng C, Gorrie C, Hayward I, Elston B, Venn M, Mackay-Sim A and Waite P (2006) Survival and migration of human and rat olfactory ensheathing cells in intact and injured spinal cord. J. Neuroscience Res. 83: 1201-12.
• Potas JR, Zheng Y, Moussa C, Vann M, Gorrie CA, Deng C and Waite PME (2006) Augmented locomotor recovery following spinal cord injury in the athymic nude rat. J. Neurotrauma 23: 660-73.
• Laird AS, Carrive C, Waite PME (2006) Cardiovascular and temperature changes in spinal cord injured rats at rest and during autonomic dysreflexia. J. Physiol 577: 539-48.
• Gorrie CA, Rodriguez M, Sachdev P, Duflou J, Waite PME (2007) Mild neuritic changes are increased in the brains of fatally injured older motor vehicle drivers. Accid Anal Prev. 39: 1114-20.
• Peisah C, Snowdon J, Gorrie C, Kril J, Rodriguez M (2007) Investigation of Alzheimer’s disease-related pathology in community dwelling older subjects who committed suicide. J Affective Dis. 99: 127-32.
• Gorrie CA, Brown J and Waite PME (2008) Crash characteristics of older pedestrian fatalities: dementia pathology may be related to 'at risk' traffic situations. Accid Anal Prev. (in press).
• Laird AS, Finch AM, Waite PME, Carrive C (2008) Peripheral changes above and below injury level lead to prolonged vascular responses following high spinal cord injury. Am. J. Phys: Heart Circ. (In press).