Traumatic brain (TBI) and spinal cord injuries (SCI) render devastating health problems in the United States with an annual cost of approximately 72 billion dollars. This has initiated an enormous focus on the development and discovery of neuroprotective and/or pro-regenerative agents for the treatment of TBI and SCI. Nevertheless, the underlying mechanism(s) of neuronal degeneration and progressive tissue destruction that occurs following such injuries are not fully understood. To begin exploring the cellular and/or molecular mechanisms underlying the pathophysiology of TBI and SCI, it is important to focus on key regulatory steps in the cell death process. Recent evidence indicates that mitochondria, long-known as the “powerhouse” of the cell, play a pivotal role in the cell death cascade. Thus, the main focus of our laboratory is to advance the field of CNS injury research by mapping key events that result in mitochondrial failure and employing this knowledge in developing novel strategies that target these pathways.

Davis, L.M., Pauly, J.R, Readnower, R, Rho, J.M., Sullivan, P.G., (2008). Fasting is Neuroprotective Following Traumatic Brain Injury. Journal of Neuroscience Research, 86, 1812-1822. Gash, D.M., Rutland, K., Carter, N., Sullivan, P.G., Bing, G., Cass, W., Pandya, J.D., Liu, M., Choi, D.Y., Hunter, R.L., Gerhardt, G.A., Smith, C.D., Slevin, J.T., Prince, T.S., (2008). Trichloroethylene: Parkinsonism and Complex 1 Mitochondrial Neurotoxicity. Annals of Neurology, 63(2), 184-192. Mbye, L., Singh, I.N., Sullivan, P.G., Springer, J.E., Hall, E.D., (2008). Attenuation of Acute Mitochondrial Dysfunction after Traumatic Brain Injury in Mice by NIM811, a Non-immunosuppressive Cyclosporin A Analog. Experimental Neurology, 209(1), 243-253. Hall, E.D., Deng, Y., Sullivan, P.G., (2008). Evolution of Post-Traumatic Neurodegeneration after Controlled Cortical Impact Traumatic Brain Injury in Mice and Rats. Journal of Neurotrauma, 25(3), 235-247. Studzinski, C.M., MacKay, W.A., Beckett, T.L., Henderson, S.T., Murphy, M.P., Sullivan, P.G., Burnham, W.M. (2008). Induction of Ketosis may Improve Mitochondrial function and Decrease steady-state Amyloid-Beta Precursor Protein (APP) Levels in the Aged Dog. Brain Research, 1226, 209-217. Nasr, P., Sullivan, P.G., Smith, G.M., (2008). Mitochondrial Imaging in Dorsal Root Ganglion Neurons following the Application of Inducible Adenoviral Vector Expressing two Fluorescent Proteins. Journal of Neuroscience Methods, 172(2), 209-217. Davis, L.M., Rho, J.M., Sullivan, P.G., (2008) UCP-Mediated Free Fatty Acid Uncoupling of Isolated Cortical Mitochondria from Fasted Animals: Correlations to Dietary Modulations. Epilepsia, 8, 117-119. Patel, S.P., Sullivan P.G., (co-first author), Pandya J.D., Rabchevsky A.G., (2009). Differential Effects of Mitochondrial Uncoupling Agent, 2-4-Dinitrophenol, or Nitroxide Antioxidant, Tempol, on Synaptic or Nonsynaptic Mitochondria after Spinal Cord Injury. Journal of Neuroscience Research, 87(1), 130-140. Reed, T.T., Owen, J., Pierce, W.M., Sebastian, A. Sullivan, P.G., Butterfield, D.A., (2009). Proteomic Identification of Nitrated Brain Proteins in Traumatic Brain-Injured Rats treated Postinjury with Gamma-glutamylcysteine Ethyl Ester: Insights into the Role of Elevation of Glutathione as a Potential Therapeutic Strategy for Traumatic Brain Injury. Journal of Neuroscience Research, 87(2), 408-417. Gilmer, L.K., Roberts, K.N., Sullivan, P.G., Miller, K., Scheff, S.W., (2009). Early Mitochondrial Dysfunction following Cortical Contusion Injury. Journal of Neurotrauma, 26(8), 1271-1280. Choi, D.Y., Liu M., Hunter R.L., Cass W.A., Pandya J.D., Sullivan P.G., Shin E.J., Kim H.C., Gash D.M., Bing G., (2009). Striatal Neuroinflammation promotes Parkinsonism in Rats. PloS One, 4(5). Geddes, J.W., Sullivan, P.G., (2009). Special Issue: Mitochondria and Neurodegeneration., Experimental Neurology, 218(2), 169-170. Pandya, J.D., Pauly, J.R., Sullivan, P.G., (2009). The Optimal Dosage and Window of Opportunity to Maintain Mitochondrial Homeostasis following Traumatic Brain Injury using the Uncoupler FCCP. Experimental Neurology, 218(2), 381-389. Head E., Nukala V.N., Fenoglio K.A., Muggenburg B.A., Cotman C.W., Sullivan P.G., (2010). Effects of Age, Dietary, and Behavioral Enrichment on Brain Mitochondria in a Canine Model of Human Aging. Experimental Neurology, 220(1) 171-176. Liu M., Choi, D.Y., Hunter R.L., Pandya J.D., Cass W.A., Sullivan P.G., Kim H.C., Gash D.M., Bing G., (2010). Trichloroethylene Induces Dopaminergic Neurodegeneration in Fisher 344 Rats. Journal of Neurochemistry,112(3), 773-783. Blalock, E.M., Grondin, R., Chen, K., Thibault, O., Thibault, V. Pandya, J.D., Dowling, A., Zhang, Z., Sullivan, P.G., Porter, N.M, Landfield, P.W., (2010). Aging-Related Gene Expression in Hippocampus Proper Compared with Denate Gyrus is Selectively Associated with Metabolic Syndrome Variables in Rhesus Monkeys. Journal of Neuroscience, 30(17), 6058-6071. Patel S.P., Sullivan P.G., Lyttle T.S., Rabchevsky A.G., (2010). Acetly-L-carnitine Ameliorates Mitochondrial Dysfunction Following Contusion Spinal Cord Injury. Journal of Neurochemistry, 114(1), 291-301. Readnower R.D., Chavko M., Adeeb S., Conroy M.D., Pauly J.R., McCarron, R.M., Sullivan P.G., (2010). Increase in Blood-Brain barrier Permeability, Oxidative Stress, and activated Microglia in a Rat Model of Blast-induced Traumatic Brain Injury. Journal of Neuroscience Research, 88(16), 3530-3539. Sauerbeck A.D., Gao J., Readnower R.D., Liu M., Pauly J.R., Bing G., Sullivan P.G., (2011). Pioglitazone Attenuates Mitochondrial Dysfunction, Cognitive Impairment, Cortical Tissue Loss, and Inflammation following Traumatic Brain Injury. Experimental Neurology, 227(1), 128-135. * Selected as “Hot Topic” article Yin, Y., Zhang, C., Goldstein, G.A., Sullivan, P.G., Smith, G.M., (2011). Directing Dopaminergic Fiber Growth along a Preformed Molecular Pathway from Embryonic Ventral Mesencephalon Transplants in Rat Brain. Journal of Neuroscience Research, 89(5), 619-627. Sauerbeck A.D., Pandya J.D., Singh I.N., Bittman, K., Readnower, R., Bing, G., Sullivan P.G., (2011). Analysis of Regional Brain Mitochondrial Bioenergetics and Susceptibility to Mitochondrial Inhibition utilizing a Microplate Based System. Journal of Neuroscience Methods, 198(1), 36-43. Sullivan, P.G., Sebastian, A.H., Hall, E.D., (2011). Therapeutic Window Analysis of the Neuroprotective Effects of Cyclosporine A after Traumatic Brain Injury. Journal of Neurotrauma, 28(2), 311-318. Pandya J. D., Sullivan P. G., Pettigrew L. C, (2011). Focal Cerebral Ischemia and Mitochondrial Dysfunction in the TNF-a Transgenic rat. Brain Research, 1384, 151-160. Akundi R. S., Huang Z., Eason J., Pandya J. D., Cass, W.A., Sullivan P. G., Büeler H., (2011). Increased Mitochondrial Calcium Sensitivity and Abnormal Expression of Immunity Genes precede Dopaminergic Defects in PINK1-Deficient Mice. PLOSONE, 6(1), e16038. Readnower R.D., Pandya J.D., McEwen M.L., Pauly J.R., Springer J.E., Sullivan P.G., (2011). Post-injury Administration of the Mitochondrial Permeability Transition Pore Inhibitor, NIM811, is Neuroprotective and Improves Cognition after Traumatic Brain Injury in Rats. Journal of Neurotrauma, 28(9), 1845-1853. Sauerbeck A.D., Hunter, R.L., Bing, G., Sullivan P.G., (2012). Traumatic Brain Injury and Trichloroethylene Exposure Interact and Produce Functional, Histological, and Mitochondrial Deficits. Experimental Neurology, 234(1), 85-94. Avery M.A., Rooney T.M., Wishart T.M., Pandya J.D., Gillingwater T.H., Geddes J.W., Sullivan P.G., and Freeman M.R., (2012). WldS prevents Axon Degeneration through increased Mitochondrial Flux and Enhanced Mitochondrial Ca2+ Buffering. Current Biology, 22(7), 596-600. Patel, S.M., Sullivan P.G., Lyttle T.S., Magnuson, D.S.K., Rabchevsky A.G., (2012). Acetyl-L-Carnitine Treatment Following Spinal Cord Injury Improves Mitochondrial Function Correlated with Remarkable Tissue Sparing and Functional Recovery. Neuroscience, 17(210), 296-307. Akundi R.S., Zhi, L., Sullivan P.G., Büeler H., (2013). Shared and Cell type-specific Mitochondrial Defects and Metabolic Adaptations in Primary Cells from PINK1-deficient Mice. Neurodegenerative Disease, 12(3), 136-149, PMID:23295771. Visavadigya, N.P., McEwen, M.L., Pandya, J.D., Sullivan, P.G., Gwag, B.J., Springer, J.E., (2013). Antioxidant Properties of Neu2000 on Mitochondrial Free Radicals and Oxidative Damage. Toxicology In Vitro, 27(2), 788-97, PMID:23268106. Pandya J.D., Nukala, V.N., Sullivan, P.G., (2013). Concentration Dependent Effect of Calcium on Brain Mitochondrial Bioenergetics and Oxidative Stress Parameters. Frontiers in Neuroscience, Neuroenergetics, Dec 18;5: 10. Pandya, J.D., Readnower, R.D., Patel, S.P., Yonutas, H.M., Pauly, J.R., Goldstein, G.A., Rabchevsky, A.G., Sullivan, P.G., (2014). N-acetylcysteine Amide Confers Neuroprotection, improves Bioenergetics and Behavioral Outcome following TBI. Experimental Neurology, 257, 106-113. * Selected as “Hot Topic” article. Patel, S.P., Sullivan, P.G., (co-first author), Pandya, J.D., Goldstein, G.A., Vanrooyen, J.L., Yonutas, H.M., Eldahan, K.C., Morehouse, J., Magnuson, D.S., Rabchevsky, A.G., (2014). N-acetylcysteineamide Preserves Mitochondrial Bioenergetics and Improves Functional Recovery following Spinal Trauma. Experimental Neurology, 257, 95-105. * Selected as “Hot Topic” article. Yonutas, H.M., Pandya, J.D., Sullivan, P.G., (2015). Changes in Mitochondrial Bioenergetics in the Brain versus Spinal Cord become more Apparent with Age. Journal of Bioenergetics and Biomembranes, 47(1-2), 149-154. Wang, W.X., Visavadigya, N.P., Pandya, J.D., Nelson, P.T., Sullivan, P.G., Springer, J.E., (2015). Mitochondria-Associated microRNAs in rat Hippocampus following Traumatic Brain Injury. Experimental Neurology, 265, 84-93. Pandya, J.D., Grondin, R., Yonutas, H.M., Haghnazar, H., Gash, D.M., Zhang, Z., Sullivan, P.G., (2015). Decreased Mitochondrial Bioenergetics and Calcium Buffering Capacity in the Basal Ganglia correlates with Motor Deficits in a Nonhuman Primate model of Aging. Neurobiology of Aging, 36(5), 1903-1913. Kim, D.Y., Abdelwahab, M.G., Lee, S.H., O'Neill, D., Thompson, R.J., Duff, H.J., Sullivan, P.G., Rho, J.M., (2015). Ketones Prevent Oxidative Impairment of Hippocampal Synaptic Integrity through KATP Channels. PLoS One, 10(4), e0119316. Kim, D.Y., Simeone, K.A., Simeone, T.A., Pandya, J.D., Wilke, J.C., Ahn, Y., Geddes, J.W., Sullivan, P.G., Rho, J.M., (2015). Ketone Bodies Mediate Antiseizure Effects through Mitochondrial Permeability Transition. Annals of Neurology, Epub