Stroke Laboratory

Tissue damage (pale areas) in rat brain following an experimental stroke

In this laboratory, we investigate the molecular basis of nerve cell loss, a major determinant of the symptoms of many brain disorders, and the responses of the brain tissue to this damage. These studies have focused particularly on the brain damage produced following stroke. A major direction in our current research is to assess the contribution of cells known as astrocytes. Under normal conditions, these cells provide many important support functions for the nerve cells that are essential for their normal activities and help to protect against damage. Our studies are examining whether astrocytes limit damage during stroke or whether their function is modified in ways that worsen the outcome. We are also investigating responses of astrocytes that develop over many weeks following a stroke and are thought to influence the ability of the damaged brain to reverse functional deficits. We are particularly interested in the role in this process of interactions between astrocytes and another type of cell known as microglia. A second focus of our research has been on the contribution to nerve cell damage of parts of the cells known as mitochondria. Mitochondria are normally the major site of the production of energy needed for cell function. These components are also often key players in promoting deleterious changes leading to the death of cells under a wide range of abnormal conditions. Our studies are aimed at characterising the changes in mitochondria following stroke and evaluating their contribution to tissue damage.

Investigators

Neil Sims, BSc(Hons), PhD

Students

Benjaporn Homkajorn, MBiotech, PhD student (co-supervised with Dr Håkan Muyderman)
Josephine Malmevik, MSc, PhD student (co-supervised with Dr Håkan Muyderman)
WeiPing Yew, BMSc(Hons), PhD student (co-supervised with Håkan Muyderman)

Contacts

Prof Neil Sims
Ph: (08) 8204 4242 Int Ph: +61 8 8204 4242 Fax: (08) 8374 0139 Int Fax: +61 8 8374 0139 Email: neil.sims@flinders.edu.au University Profile Page

Research Projects

• Glial cell contributions to restoration of function following stroke
• Modulation of gene expression in astrocytes and microglia
• Mitochondrial glutathione and brain cell death

Collaborative Research

Dr Håkan Muyderman (Flinders University) and Prof Michael Nilsson (Göteborg University): Astrocytic contributions to tissue damage and recovery in stroke and the roles of mitochondrial glutathione in neural cells.

Dr Håkan Muyderman (Flinders University), Prof Michael Nilsson (Göteborg University) and Prof Robert Rush (Flinders University): Selective gene modulation in astrocytes and microglia in vivo.

Selected Recent Publications

Muyderman H, Yew WP, Homkajorn B and Sims NR (2010) Astrocytic responses to DNA delivery using Nucleofection. Neurochem Res, 35:1771-1779

Homkajorn B, Sims NR and Muyderman H (2010) Connexin 43 regulates astrocytic migration and proliferation in response to injury. Neurosci Lett, 486:197-201

Sims NR and Muyderman H (2010) Mitochondria, oxidative metabolism and cell death in stroke. Biochim Biophys Acta, 1802(1):80-91

Lee DR, Helps SC, Macardle PJ, Nilsson M and Sims NR (2009) Alterations in membrane potential in mitochondria isolated from brain subregions during focal cerebral ischemia and early reperfusion: Evaluation using flow cytometry. Neurochem. Res. 34, 1857-1866

Wadey AL, Muyderman H, Kwek PT and Sims NR (2009) Mitochondrial glutathione uptake: characterization in isolated brain mitochondria and astrocytes in culture. J. Neurochem. 109, S1 101-108

Sims NR and Anderson MF (2008) Isolation of mitochondria from rat brain using Percoll density gradient centrifugation. Nature Protocols, 3, 1228-1239

Helps SC, Sims NR (2007) Inhibition of nitric oxide synthase with 7-nitroindazole does not modify early metabolic recovery following focal cerebral ischemia in rats. Neurochem Res. 32(4-5):663-70

Muyderman H, Wadey AL, Nilsson M, Sims NR (2007) Mitochondrial glutathione protects against cell death induced by oxidative and nitrative stress in astrocytes. J Neurochem. 102(4):1369-82

 

Updated June 28, 2011