Sims, Neil - Flinders University - Department of Medical Biochemistry

研究领域

Current research focuses on the responses of cells in brain tissue surrounding focal areas of damage that are typically generated by a stroke. Nerve cells in these tissue regions show adaptive changes which apparently contribute to spontaneous improvements in neurological function that are commonly seen during the first few months following a stroke. Researchers in the Sims group are investigating changes in the two major populations of support cells, the astrocytes and microglia, and testing whether modifying these changes can increase adaptation in the nerve cells and further promote recovery of neurological function. These studies involve the use of animal models of stroke as well as a newly-developed model of focal injury in brain cells grown in culture. Techniques routinely used include subcellular fractionation, immunohistochemistry, fluorescence microscopy, Western blots and analyses of enzyme activities and metabolites. The research group is also investigating and developing techniques for selectively manipulating the expression of individual proteins in astrocytes or microglia in the brain in vivo.

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Malmevik, J., Rogers, M.L., Nilsson, M., Nakanishi, Y., Rush, R.A., Sims, N.R., et al. (2014). Selective transfection of microglia in the brain using an antibody-based non-viral vector. Brain Research, 1586 pp. 12-22. [Scopus] Muyderman, H., Sims, N.R., Tanaka, M., Fuku, N., Raghupathi, R. and Thyagarajan, D. (2012). The mitochondrial T1095C mutation increases gentamicin-mediated apoptosis. Mitochondrion, 12(4) pp. 465-471. [10.1016/j.mito.2012.06.006] [Scopus] Wang, X., Leverin, A.L., Han, W., Zhu, C., Johansson, B., Jacotot, E., et al. (2011). Isolation of brain mitochondria from neonatal mice. Journal of Neurochemistry, 119(6) pp. 1253-1261. [10.1111/j.1471-4159.2011.07525.x] [Scopus] Homkajorn, B., Sims, N.R. and Muyderman, H.C. (2010). Connexin 43 regulates astrocytic migration and proliferation in response to injury. Neuroscience Letters, 486 pp. 197-201. [10.1016/j.neulet.2010.09.051] [Scopus] Muyderman, H.C., Yew, W.P., Homkajorn, B. and Sims, N.R. (2010). Astrocytic responses to DNA delivery using Nucleofection. Neurochemical Research, 35 pp. 1771-1779. [10.1007/s11064-010-0243-y] [Scopus] Sims, N.R. and Muyderman, H.C. (2010). Mitochondria, oxidative metabolism and cell death in stroke. Biochimica et Biophysica Acta-Molecular Basis of Disease, 1802(1) pp. 80-91. [10.1016/j.bbadis.2009.09.003] [Scopus] Lee, D., Helps, S.C., MacArdle, P.J., Nilsson, M. and Sims, N.R. (2009). Alterations in membrane potential in mitochondria isolated from brain subregions during focal cerebral ischemia and early reperfusion: evaluation using flow cytometry. Neurochemical Research, 34(10) pp. 1857-1866.[10.1007/s11064-009-0001-1] [Scopus] Wadey, A.L., Muyderman, H.C., Kwek, P.T. and Sims, N.R. (2009). Mitochondrial glutathione uptake: characterization in isolated brain mitochondria and astrocytes in culture. Journal of Neurochemistry, 109(Suppl. 1) pp. 101-108. [10.1111/j.1471-4159.2009.05936.x] [Scopus] Sims, N.R. and Anderson, M.F. (2008). Isolation of mitochondria from rat brain using Percoll density gradient centrifugation. Nature Protocols, 3(7) pp. 1228-1239. [10.1038/nprot.2008.105] [Scopus] Helps, S.C. and Sims, N.R. (2007). Inhibition of nitric oxide synthase with 7-nitroindazole does not modify early metabolic recovery following focal cerebral ischemia in rats. Neurochemical Research, 32(4-5) pp. 663-670. [10.1007/s11064-006-9160-5] [Scopus] Muyderman, H.C., Wadey, A.L., Nilsson, M. and Sims, N.R. (2007). Mitochondrial glutathione protects against cell death induced by oxidative and nitrative stress in astrocytes. Journal of Neurochemistry, 102(4) pp. 1369-1382. [10.1111/j.1471-4159.2007.04641.x] [Scopus] Thoren, A.E., Helps, S.C., Nilsson, M. and Sims, N.R. (2006). The metabolism of 14C-glucose by neurons and astrocytes in brain subregions following focal cerebral ischemia in rats. Journal of Neurochemistry, 97(4) pp. 968-978. [10.1111/j.1471-4159.2006.03778.x] [Scopus] Rahman, R.M., Nair, S.M., Helps, S.C., Shaw, O.M., Sims, N.R., Rosengren, R.J., et al. (2005). (-)-Epigallocatechin gallate as an intervention for the acute treatment of cerebral ischemia. Neuroscience Letters, 382(3) pp. 227-230.[10.1016/j.neulet.2005.03.018] [Scopus] Thoren, A.E., Helps, S.C., Nilsson, M. and Sims, N.R. (2005). Astrocytic function assessed from 1-C-14 - acetate metabolism after temporary focal cerebral ischemia in rats. Journal of Cerebral Blood Flow and Metabolism, 25(4) pp. 440-450.[10.1038/sj.jcbfm.9600035] [Scopus] Muyderman, H.C., Nilsson, M. and Sims, N.R. (2004). Highly selective and prolonged depletion of mitochondrial glutathione in astrocytes markedly increases sensitivity to peroxynitrite. Journal of Neuroscience, 24(37) pp. 8019-8028. [10.1523/JNEUROSCI.1103-04.2004] [Scopus] Anderson, M.F., Nilsson, M., Eriksson, P.S. and Sims, N.R. (2004). Glutathione monoethyl ester provides neuroprotection in a rat model of stroke. Neuroscience Letters, 354(2) pp. 163-165.[10.1016/j.neulet.2003.09.067] [Scopus] Anderson, M.F., Nilsson, M. and Sims, N.R. (2004). Glutathione monoethylester prevents mitochondrial glutathione depletion during focal cerebral ischemia. Neurochemistry International, 44(3) pp. 153-159. [10.1016/S0197-0186(03)00133-5] [Scopus] Sims, N.R., Nilsson, M. and Muyderman, H.C. (2004). Mitochondrial glutathione: a modulator of brain cell death. Journal of Bioenergetics and Biomembranes, 36(4) pp. 329-333.[10.1023/B:JOBB.0000041763.63958.e7] [Scopus] Zaidan, E., Nilsson, M. and Sims, N.R. (2004). Increased mitochondrial permeability in response to intrastriatal N-methyl-D-aspartate : detection based on accumulation of radiolabel from[3h]deoxyglucose. Neurochemical Research, 29(3) pp. 609-616.[10.1023/B:NERE.0000014831.65991.6a] [Scopus] Lee, D., Helps, S.C., Gibbins, I.L., Nilsson, M. and Sims, N.R. (2003). Losses of NG2 and NeuN immunoreactivity but not astrocytic markers during early reperfusion following severe focal cerebral ischemia. Brain Research, 989(2) pp. 221-230.[10.1016/S0006-8993(03)03373-0] [Scopus]