Department of Neuroscience

Research Abstract

1. Neuronal and glial cell degeneration
Blockade of NMDA glutamate receptors and activation of GABA receptors during late fetal or early neonatal life trigger widespread apoptotic neurodegeneration in the developing brain of mammals. Our studies also suggested that glutamate, acting at NMDA receptors, controls neuronal survival. We further clarified the deleterious effect of ethanol (with NMDA receptor antagonist & GABA receptor agonist actions) on the developing brain. We have characterized the robust neuronal apoptotic cell death caused by these agents and were able for the first time to give very detailed electron microscopic description of the stages of programmed cell death in cortical, brainstem and cerebellar neurons. We demonstrated these effects also in primates... read more

Selected Publications

• K. Dikranian and P. Bridgman, Guide to Medical Histology, iTunes, 2015.
• Dikranian, K., Holtzman, DM. (2014) Editorial, The ultrastructural identity of Alzheimer’s pathology: Lessons from animal models. Journal of Neurological Disorders. 2, (3).
• Van Essen D, Glasser M, Chen C, Dikranian D,. Sotiropoulos S, Jbabdi S, and Behrens T. Mapping Connections in Humans and Nonhuman Primates: Aspirations and Challenges for Diffusion Imaging. Diffusion MRI, Second Edition Johansen-Berg and Behrens, eds, Ch. XVI, pp 336- 356, Elsevier, 2013.
• Creeley C, Dikranian K, Dissen G, Martin L, Olney J, Brambrink A.(2013) Propofol induced apoptosis of neurones and oligodendrocytes in fetal and neonatal rhesus macaque brain. Br. J. Anaesth. 110, Suppl.1:29-38.
• Musiek E. S., Lim M, Yang G, Bauer A, Qi L, Lee Y, Roh J, Xilma Ortiz-Gonzalez, Dearborn, J., Culver C., Herzog E, Hogenesch J, Wozniak D, Dikranian K,. Giasson B, Weaver D, Holtzman D.M. , FitzGerald G, (2013) Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration. Journal of Clinical Investigation. 123: 5389-5400.
• Dikranian K, Kim J, Stewart FR, Levy MA, Holtzman, DM. (2012) Ultrastructural studies in APP/PS1 mice expressing human ApoE isoforms: implications for Alzheimer’s disease, Int. J. Clin. Exp. Pathol. 5(6):482-495.
• Christensen H, Dikranian K, Li A, Baysac K, Walls K, Olney J, Roth K, Harris D. (2010), A highly toxic cellular prion protein induces a novel, non-apoptotic form of neuronal death. Am J. Pathol. 176:2695-2706.
• Dikranian K, Cohen R, MacDonald C, Pan Y, Brakefield D, Bayly P, Parsadanian A (2008) Mild traumatic brain injury to the infant mouse causes robust white matter axonal degeneration which precedes apoptotic death of cortical and thalamaic neurons. Exp. Neurol. 211:551-560.
• MacDonald CL, Dikranian K, Bayly P, Holtzman D, Brody D (2007) Diffusion tensor imaging reliably detects experimental traumatic axonal injury and indicates approximate time of injury. J. Neurosci. 27:11869-11876.
• Dikranian K, Qin Y, Labruyere J, Nemmers B, Olney J (2005) Ethanol-induced apoptotic cell death in the developing rodent cerebellum and related brainstem structures. Dev. Brain. Res. 155:1-13.
• Dikranian K, Ishimaru M, Tenkova T, Labuyere J, Qin YO, Ikonomidou C, Olney J (2001) Apoptosis in the in vivo mammalian forebrain. Neurobiol Dis. 8:359-379. Review.
• Ikonomidou CH, Bittigau P, Ishimaru M, Wozniak D, Koch CH, Genz K, Price M, Stefovska V, Hoster F, Tenkova T, Dikranian K, Olney J (2000) Ethanol-Induced Apoptotic Neurodegeneration and the fetal alcohol syndrome, Science. 287:1056-60.
• Steudel W, Watanabe M, Dikranian K, Jacobson M, Jones R (1999) Expression of nitric oxide synthase isoforms (NOS II and NOS III) in adult rat lung in hyperoxic pulmonary hypertension. Cell Tissue Research. 295:317-329.
• Ikonomidou CH, Bosh F, Miksa M, Bittigau P, Volker J, Dikranian K, Tenkova T, Stefovska V, Turski L, Olney J (1999) Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science. 283:70-74.
• Jevtovic-Todorovic, Todorovic SM, Mennerick S, Powell S, Dikranian K, Benshoff N, Zorumski C, Olney JW (1998) Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nature Medicine. 4:460-463.
• Dikranian K, Loesch A, Burnstock G (1994) Localization of nitric oxide synthase and its colocalisation with vasoactive peptides in coronary and femoral arteries. An electron microscope study. J Anat. (Lond.), 184 (Pt 3):583-590.

For a complete list of Dr. Dikranian's publications, click here.