Associate Professor of Anatomy
Anatomy and Neurobiology
Neurodegeneration in the Developing and Aged Brain
My current research includes collaborative studies with the Department of Psychiatry, Department of Neurology and the Department of Biomechanical Engineering. We have shown that during brain synaptogenesis there are several mechanisms by which massive neurodegeneration can be induced in the developing brain. Insufficient activation of NMDA glutamate receptors or excessive activation of GABA-A receptors triggers widespread apoptotic neurodegeneration. Ethanol, with both NMDA receptor blocking and GABA-A receptor activating properties, also causes widespread apoptotic neurodegeneration throughout the developing forebrain during synaptogenesis including the cortex, various brain stem nuclei as well as in the cerebellum. This provides an explanation for the reduced brain mass and lifelong neurobehavioral disturbances associated with the human fetal alcohol syndrome. Based on our data we were able to characterize by EM criteria the progression of apoptotic cell death in the developing CNS. Additionally we are following the role of excitatory transmitters in memory, aging and dementia as well as comparing the ultrastructural morphology of autopsy/biopsy specimens from Alzheimer brains and brains of genetically altered mice. My current research focuses also on the mechanisms and mechanical forces (strain fields) that trigger acute and protracted cell death in traumatic brain injury conditions and compares patterns of neurodegeneration mechanisms in newborn and adult animals. I am investigating also the role of neurotrophic factors such as GDNF on brain trauma-induced neuronal cell death.
Christensen HM, Dikranian K, Li A, Baysac KC, Walls KC, Olney JW, Roth KA, Harris DA (2010 Jun). A highly toxic cellular prion protein induces a novel, nonapoptotic form of neuronal death. Am J Pathol. 176 (6): 2695-706. Full Article >
Dikranian K, Cohen R, Mac Donald C, Pan Y, Brakefield D, Bayly P, Parsadanian A (2008 Jun). Mild traumatic brain injury to the infant mouse causes robust white matter axonal degeneration which precedes apoptotic death of cortical and thalamic neurons. Exp Neurol. 211 (2): 551-60. Full Article >
Mac Donald CL, Dikranian K, Bayly P, Holtzman D, Brody D (2007 Oct 31). Diffusion tensor imaging reliably detects experimental traumatic axonal injury and indicates approximate time of injury. J Neurosci. 27 (44): 11869-76. Full Article >
Dikranian K, Qin YQ, Labruyere J, Nemmers B, Olney JW (2005 Mar 22). Ethanol-induced neuroapoptosis in the developing rodent cerebellum and related brain stem structures. Brain Res Dev Brain Res. 155 (1): 1-13. Full Article >
Dikranian K, Ishimaru MJ, Tenkova T, Labruyere J, Qin YQ, Ikonomidou C, Olney JW (2001 Jun). Apoptosis in the in vivo mammalian forebrain. Neurobiol Dis. 8 (3): 359-79. Full Article >
Ikonomidou C, Bittigau P, Ishimaru MJ, Wozniak DF, Koch C, Genz K, Price MT, Stefovska V, Hörster F, Tenkova T, Dikranian K, Olney JW (2000 Feb 11). Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science. 287 (5455): 1056-60. Full Article >
Krikor Dikranian, M.D., Ph.D.
Office Location: 452 McDonnell Science
Office Phone: 314-362-3548
Campus Box: 8108