Stroke and Spinal Cord Injury Laboratory
Laboratory Head
Professor Bevyn Jarrott PhD (Camb) BPharm Hons (Qld)
Contact Details
Email: | |
Phone: | +61 (0)3 8344 1956 |
Fax: | +61 (0)3 9347 0446 |
Number of
Staff: 2 (Postdoctoral Fellows)
Students: 1 (Postgraduate research students)
Research Interests
- The rational design, synthesis and evaluation of novel neuroprotective drugs to reduce or delay the onset of a range of neurodegenerative disorders such as Parkinson’s and Huntington’s disease, multiple sclerosis, stroke and neuropathic pain.
- Assessment of biomarkers in blood to follow the progress of neurodegenerative disorders in animal models as a method of validating the dosage and time course of treatment with novel neuroprotective drugs.
- Development of fluorescent ligands to image neurodegenerative disorders in living animals by fluorescence tomography.
Current Projects
- After spinal cord injury there is an increase in the number of sodium channels in cells that cause inflammation at the site of damage and so blocking these sodium channels should reduce swelling and nerve damage. In our laboratory we have discovered some highly potent sodium channel blockers and so we are now assessing the ability of these novel sodium channel blockers to minimise the extent of paralysis in the spinal cord of rats after a controlled compression of the spinal cord. This will provide information so that a decision can be made if these drugs have a clinical application in reducing disability after spinal cord trauma after road accidents or diving accidents.
- In order to reduce the onset of chronic neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases and multiple sclerosis, we are developing a new type of neuroprotective drug that has not previously been examined as therapy for these neurological disorders. The drugs increase the nerves’ natural defence against free radicals that arise during inflammatory processes and should therefore slow the degeneration of nerves.
Laboratory Techniques
- In anesthetised rats, it is possible to make a reproducible and controlled injury to the spinal cord using a miniature balloon which is inflated to a defined size that will compress the spinal cord for a defined period of time. The extent of reduction in movement of the rats is then determined at different times after the surgery by video recordings. The experimental drug is administered at different times and at different doses after compression of the spinal cord so that it can be determined how soon after spinal cord trauma the drug needs to be administered in order to provide protection against disability. Quantitative histological analysis of the damage to the spinal cord is used to define if the drugs are able to minimise damage and speed up the restoration of motor activity in the rats.
- Rats are anesthetised and a chemical that produces inflammation in the brain is injected in small volumes into the area of the brain that is affected in Parkinson’s disease. The time course of the death of dopamine nerves in the inflamed area is then measured. Rats are then injected with the experimental drug and the optimal dose and frequency of administration of the drug is determined that increases antioxidant defence enzymes using biochemical techniques. Once this has been found, the drug is administered prior to the inflammatory chemical and the reduction in death of dopamine nerves is determined after injection of the inflammatory chemical. Behavioural tests are also applied to confirm that the drug has reduced the symptoms of Parkinson’s disease. If the drug acts as predicted, it will then be tested in other rodent neurological disease models such as Alzheimer’s disease and multiple sclerosis.
Funding
- National Health & Medical Research Council of Australia
- Victorian Neurotrauma Initiative of the Transport Accident Commission
Recent Publications
Weston RM, Jones NM, Jarrott B, & Callaway JK. (2007)
Inflammatory cell infiltration after endothelin-1-induced cerebral ischemia:
histochemical and myeloperoxidase correlation with temporal changes in brain
injury. J Cereb Blood Flow Metab. 27:100-114
Weston RM, Jarrott B, Ishizuka Y, & Callaway JK. (2006)
AM-36 modulates the neutrophil inflammatory response and reduces breakdown of the blood brain barrier after endothelin-1 induced focal brain ischaemia. Br J Pharmacol. 149:712-723.
Gresle MM, Jarrott B, Jones NM, & Callaway JK. (2006)
Injury to axons and oligodendrocytes following endothelin-1-induced middle
cerebral artery occlusion in conscious rats. Brain Res. 1110:13-22
Jones NM, Lee EM, Brown TG, Jarrott B, & Beart PM. (2006)
Hypoxic preconditioning produces differential expression of hypoxia-inducible
factor-1alpha (HIF-1alpha) and its regulatory enzyme HIF prolyl hydroxylase 2 in
neonatal rat brain. Neurosci Lett. 404:72-77.
O'Shea RD, Lau CL, Farso MC, Diwakarla S, Zagami CJ, Svendsen BB, Feeney SJ,
Callaway JK, Jones NM, Pow DV, Danbolt NC, Jarrott B, & Beart PM. (2006)
Effects of lipopolysaccharide on glial phenotype and activity of glutamate
transporters: Evidence for delayed up-regulation and redistribution of GLT-1.
Neurochem Int. 48:604-610.
Research
