Axonal Regeneration, Synaptic Plasticity, Recovery of Function
Our laboratory is interested in the basic mechanisms of neural plasticity that underlie the recovery of function after injury to the CNS. These mechanisms include collateral sprouting of intact axons in response to degeneration of converging projections, restitution of function through the use of redundant systems to replace a lost system, and regeneration leading to restoration of function. We are particularly interested in the use of transplants of fetal tissue or genetically modified cells to encourage regeneration leading to recovery of motor function. The transplants act by rescuing neurons that are destined to die and by permitting regeneration of some axons into the transplant and in some cases into the host. The function that recovers in neonates includes locomotion that is adaptable and flexible. In adults with spinal lesions, fetal transplants also rescue axotomized neurons destined to die but regeneration is much more modest. The functional recovery is also much poorer. Using cells genetically modified to secrete trophic factors instead of unmodified fetal tissues increases neuronal survival, axonal regeneration and sprouting and functional recovery after in adults. The motor recovery can be further enhanced by administration of agents that mimic transmitters, such as serotonin, that normally act as modulators of motor function.
Marion Murray, Professor of Neurobiology and Anatomy, received her PhD in Physiology from the University of Wisconsin. She has served on NIH Study sections, on the VA Office of Regeneration Research Advisory Board, on the Spinal Cord Research Foundation Advisory Board, and on the Editorial Boards of Experimental Neurology, Journal of Comparative Neurology, Neurorehabilitation and Neural Repair and Restorative Neurology and Neuroscience. She is the recipient of a Javits Neurosciences Investigator Award and a Fogarty Fellowship. She received the Trustees Award for Excellence in Teaching: Graduate School, and the Research Achievement Award from MCP Hahnemann University Dr. Murray has been visiting scientist at the Medical Research Council in London, National Defense Medical College in Taiwan, and College de France in Paris.
Miya D, Tessler A, Giszter, S, Mori F, Murray M. 1997. Fetal transplants alter the development of function after spinal cord transection in newborn rats J Neurosci17:4856-72. (abstract)
Liu Y, Kim D, Himes BT, Chow SY, Schallert T, Murray M,Tessler A, Fischer I. (1999). Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons. J Neurosci 19:4370-87. (abstract)
Kim D, Adipudi V, Giszter S, Shibayama M, Tessler A, Murray M, Simanksy KJ. (1999). Direct agonists for serotonin (5-HT 2) receptors enhance locomotor function in rats that received neural transplants after neonatal spinal transection. J Neurosci 19:6213-24. (abstract)
Murray M. 2001. Therapies to promote CNS repair. In Axonal Regeneration in the Central Nervous System. Nerve Regeneration (eds. N. Ingoglia, M. Murray) Marcel Dekkar, NYC.
Murray M and Fischer I 2001. Transplantation and gene therapy: combined approaches for repair of spinal cord injury. The Neuroscientist. 7:28-41 (abstract)
Tobias CA, Dhoot, NO, Wheatley MA, Tessler A, Murray M and Fischer I. 2001 Grafting of encapsulated BDNF-producing fibroblasts into the injured spinal cord without immune suppression in adult rats. J. Neurotrauma. 18:287-301. (abstract)
Kim D, Schallert T, Liu Yi. Browarak,T, Nayeri N, Tessler A, Fischer I, Murray, M. 2001. Transplantation of genetically modified fibroblasts expressing BDNF in adult rats with a subtotal hemisection improves specific motor and sensory functions. Neurorehabilitation and Neural Repair. 15:141-150.
Murray M, 2002. Cellular transplants: steps toward restoration of function in spinal injured animals. Progress in Brain Research. (In press) Cellular Transplants: Steps Toward Restoration of Function in Spinal Injured Animals.
Murray M, Kim D, Liu Y, Tobias C, Tessler A, Fischer I. 2002. Transplantation of genetically modified cells contributes to repair and recovery from spinal injury. Brain Res. Reviews. In press. (abstract)
Liu Y, Himes BT, Murray M, Tessler A, Fischer I. 2002 Grafts of BDNF-producing
fibroblasts that promote regeneration of axotomized rubrospinal neurons also
rescue most neurons from retrograde death and prevent their atrophy.
Experimental Neurol. 178:150-164
Eric D. Schwartz), Jed S. Shumsky, Suzanne Wehrli), Alan Tessler, Marion Murray, David B.
Hackney 2003. Ex vivo MR determined apparent diffusion coefficients correlate with motor recovery mediated by intraspinal transplants of fibroblasts genetically modified to express BDNF. Experimental Neurology. 182:49-63 (abstract)
Tobias CA, Shumsky JS, Shibata M, Tuszynski MH, Fischer I, Tessler A, Murray
M. 2003. Delayed grafting of BDNF and NT-3 producing fibroblasts into the
injured spinal cord stimulates sprouting, partially rescues axotomized red
nucleus neurons from loss and atrophy and provides limited regeneration. Exp.
Shumsky JS, Tobias CA, Tumolo M, Long WD, Giszter SF, Murray M. 2003. Delayed transplantation of fibroblasts genetically modifie to secrete BDNF and NT-3 into a spinal cord injury site is associated with limited recovery of function. Exp. Neurol. 187:114-124. (abstract)
Murray M, Tobias CA. 2003. Regeneration and sprouting in the injured spinal cord. Topics in Spinal Cord Injury Rehabilitation. 8:37-51.
Murray M. 2003 Organization of the Spinal Cord. In. Neurosciences in Medicine (ed. M. Conn).
Murray, M, Fischer I, Smeraski C, Tessler A, Giszter S. 2004. Towards a definition of recovery of function. J. Neurotrauma. 21:405-413 (abstract)
Murray M, 2004. Cellular transplants: steps toward restoration of function in spinal injured animals. Progress in Brain Research 143:133-146. (abstract)
Murray M. 2004. Molecular mechanisms of axonal regeneration in the central nervous system. Advanced Studies in Medicine 4:S335-8.
C.A. Tobias1, S.S.W. Han1, J.S. Shumsky1, D. Kim4, M. Tumolo1, A. Tessler1,2, and M. Murray1 2005. Alginate Encapsulated BDNF-Producing Fibroblast Grafts Permit Recovery of Function After Spinal Cord Injury in the Absence of Immune Suppression. J. Neurotrauma 22:138-157. (abstract)
Schwartz, E.D.; Chin, C.-L.; Shumsky, J.S.; Jawad, A.F.l Brown, B.K.; Wehrli, S.; Tessler, A.; Murray, M.; Hackney, D.B. Apparent diffusion coefficients within spinal cord transplants and surroundling whit matter correlate with axonal dieback following injury. Am. J. Neuroradiol. (in press).
Shumsky, J.S.; Kao, T.; Amato, N.; Simansky, K.; Murray, M.; Moxon, K.A. Partial 5-HT1A receptor agonist activity by the 5-HT2C receptor antagonist SB 206,553 is revealed in rats spinalized as neonates. Exp Neurol. (in press).
Anderson DK, Beattie M, Blesch A, Bresnahan J, Bunge M, Dietrich D, Dietz V, Dobkin B, Fawcett J, Fehlings M, Fischer I, Grossman R, Guest J, Hagg T, Hall ED, Houle J, Kleitman N, McDonald J, Murray M, Privat A, Reier P, Steeves J, Steward O, Tetzlaff W, Tuszynski sMH, Waxman SG, Whittemore S, Wolpaw J, Young W, Zheng B. 2005. Recommended guidelines for studies of human subjects with spinal cord injury. Spinal Cord. 2005 12; (abstract)
Goldberger, M.E., A. Gorio and Murray, M. (eds.) Development and Plasticity of the Mammalian Spinal Cord. Liviana Press, Italy.1985
Ingoglia, N. And Murray M. (Eds). Axonal Regeneration in the Vertebrate CNS. Marcel Dekker. New York, 2001.