Ph.D., State University of New York at Binghamton (1984);
Postdoctoral training at University of Rochester Medical School (1984-1988);
Vice Chair of Research and Professor of Physical Medicine and Rehabilitation
Cardinal Hill Endowed Chair in Neurorehabilitation
Mitochondrial Function and Cell Death in Traumatic Spinal Cord and Brain Injury
It has been well documented that widespread neuronal and glial cell death occurs following traumatic spinal cord and brain injury. In addition, important advances have been made in understanding the intracellular pathways controlling cell death after injury. The goal of our research is to limit neuronal and glial cell loss and the resulting neurological deficits by blocking steps occurring early in the cell death process. Recently, we have focused our efforts on identifying the mitochondrial events responsible for regulating cell survival and death. We are particularly interested in identifying therapeutic agents that limit mitochondrial dysfunction as a means of promoting cell survival, and currently testing a novel agent targeting mitochondrial function in the acute phase of spinal cord injury. Our research program works closely with various Departments and Centers at the University of Kentucky and the Cardinal Hill Rehabilitation Hospital to ensure that highly promising lab bench discoveries reach the clinic.
Springer, J.E., Azbill, R.D., and Knapp, P.E. Activation of the caspase-3 apoptotic cascade in spinal cord trauma. Nature Medicine: 5, 943-946, 1999.
Nottingham, S.A., Knapp, P.E., and Springer, J.E. FK506 treatment inhibits caspase-3 activation and promotes oligodendroglial survival following traumatic spinal cord injury. Exp. Neurol. 177(1):242-251, 2002.
Nottingham, S.A. and Springer, J.E. Kainic acid infusions induce caspase-3 activation and cell death of oligodendroglia in rat spinal cord. J. Comp. Neurol. 464(4):463-471, 2003.
Sullivan, P.G., Springer, J.E., Hall, E.D., and Scheff, S.W. Mitochondrial uncoupling as a therapeutic target following neuronal injury. J. Bioenergetics and Biomembranes 36(4):353-356, 2004.
Jin, Y., McEwen, M.L., Nottingham, S., Maragos, W.F., Dragicevic, N.B., Sullivan, P.G., and Springer, J.E. The mitochondrial uncoupling agent 2,4-dinitrophenol improves mitochondrial function, attenuates oxidative damage and increases white matter sparing in the contused spinal cord. J. Neurotrauma 21(10):1396-1404, 2004.
Hall, E.D., and Springer, J.E. Neuroprotection and acute spinal cord injury: a reappraisal. NeuroRx: The Journal of the American Society for Experimental NeuroTherapeutics 1:80-100, 2004.
Sullivan, P.G., Rabchevsky, A.G., Waldmeier, P.C., and Springer, J.E. Mitochondrial permeability transition in CNS trauma: Cause or effect of neuronal cell death?Journal of Neuroscience Res. 79:231-239, 2005.
McEwen, M.L. and Springer, J.E. Time course of caspase-3 activation following traumatic spinal cord injury. Journal of Histochemistry and Cytochem. 53(7):809-819, 2005.
McEwen, M.L. and Springer, J.E. Quantification of locomotor recovery following spinal cord contusion in adult rats. Journal of Neurotrauma, 23(11):1632-1653, 2006.
McEwen, M.L., Sullivan, P.G., and Springer, J.E. Pretreatment with the cyclosporin derivative, NIM811, improves mitochondrial function following spinal cord contusion in rats. Journal of Neurotrauma, 24(4):613-624, 2007.
Ravikumar, R., McEwen, M.L., Sullivan, P.G., and Springer, J.E. Postinjury treatment with NIM811 reduces markers of apoptotic cell death and improves tissue sparing. Journal of Neurotrauma, 24(10):1618-1630, 2007.
Mbye, L.H., Singh, I.N., Carrico, K.M., Sullivan, P.G., Springer, J.E., and Hall, E.D. Attenuation of acute mitochondrial dysfunction after traumatic brain injury in mice by NIM811, a non-immunosuppressive cyclosporin A analog. Exp. Neurology, 209(1):243-253, 2008.
Pettigrew, L. C., Holtz, M., Kryscio, R., Foster, T., Springer, J.E., Li, Yizhao, Y-J., Craddock, S., Song, X-H., Grass, D., and Kindy, M. The TNF-alpha transgenic rat: A new model of cytokine-mediated ischemic brain injury. Journal of Inflammation, 23(5):47-57, 2008.