Neurobiology, Plasticity, Regeneration
The goal of my research has been to understand the mechanisms that contribute to recovery after spinal cord injury and to use this knowledge to develop rational clinical treatments. Since recovery is likely to be enhanced both by rescuing damaged neurons that otherwise would have died and by enhancing regeneration of injured axons that otherwise would not have grown in the CNS, we study and seek to enhance both neuron survival and regeneration. Our emphasis now is to use as transplants various types of cells that have been genetically modified to express neurotrophic factors, including fibroblasts, bone marrow stem cells and neural stem cells. We have found that fibroblasts and neural stem cells that have been engineered to express NT-3 rescue Clarke's nucleus neurons as efficiently as transplants of fetal spinal cord. We have also reported that fibroblasts that express BDNF rescue axotomized red nucleus neurons and in addition promote regeneration of rubrospinal axons and recovery of forelimb and hindlimb locomotor function. We intend to continue similar experiments in which we assay the effects of transplants with quantitative anatomical tracing techniques and quantitative assays of behavior. The effects of spinal cord stem cells will be particularly interesting because such cells may be extremely supportive of axon regeneration. We have begun to apply these techniques to chronic injury models, and we plan to continue these studies.
Alan Tessler received his M.D. degree from New York University and his postgraduate training in neurosurgery and neurology at the Hospital of the University of Pennsylvania. Since finishing training, Dr. Tessler has been a staff neurologist at Philadelphia's Department of Veterans Affairs Medical Center and carries out his research there and in the Department of Anatomy and Neurobiology at the MCP/Hahnemann University, where he is now Professor.
Shibayama, M., N. Matsui, B.T. Himes, M. Murray, and A. Tessler. 1998. Critical interval for rescue of axotomized neurons by transplants. NeuroReport.9 (1): 1-4. (abstract)
Takahashi, K., E. Schwarz, C. Ljubetic, M. Murray, A. Tessler, and R.A. Saavedra. 1999. A DNA plasmid that codes for human Bcl-2 gene preserves axotomized Clarke's nucleus neurons and reduces atrophy after spinal cord hemisection in adult rats. J. Comp. Neurol. 404: 159-171. (abstract)
Iwaya, K., K. Mizoi, A. Tessler, and Y. Itoh. 1999. Neurotrophic agents in fibrin glue mediate adult dorsal root regeneration into spinal cord. Neurosurgery 44: 589-596.
Liu, Y., D. Kim, B.T. Himes, S.Y. Chow, H. Jin, M. Murray, A. Tessler, and I. Fischer. 1999. Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons. J. Neurosci. 19 (11): 4370-4387. (abstract)
Zhou, L. T. Connors, D.F. Chen, M. Murray, A. Tessler, P. Kambin, and R.A. Saavedra. 1999. Red nucleus neurons of Bcl-2 over-expressing mice are protected from cell death induced by axotomy. NeuroReport 10: 3417-3421. (abstract)
Jin, Y., A. Tessler, I. Fischer, and J.D. Houle. 2000. Fibroblasts genetically modified to produce BDNF support regrowth of chronically injured serotonergic axons. Neurorehab. Neural Repair 14: 319-330. (abstract)
Chow, S.Y., J. Moul, C. A. Tobias, B. T. Himes, Y. Liu, M. Obrocka, L. Hodge, A. Tessler, and I. Fischer. 2000. Characterization and intraspinal grafting of EGF/bFGF dependent neurospheres derived from embryonic rat spinal cord. Brain Res. 874: 87-106. (abstract)
Tobias, C.A., N.O. Dhoot, R.A. Wheatley, A. Tessler, M. Murray, and I. Fischer. 2001. Grafting of encapsulated BDNF-producing fibroblasts into the injured spinal cord without immune suppression in adult rats. J. Neurotrauma 18: 287-301. (abstract)
Himes, B.T., Y. Liu, J.M. Solowska, I. Fischer, and A. Tessler. 2001. Transplants of cells genetically modified to express neurotrophin-3 (NT-3) rescue axotomized Clarke's nucleus neurons after spinal cord hemisection in adult rats. J. Neurosci. Res. 65: 549-564. (abstract)
Liu, Y., B.T. Himes, M. Murray, A. Tessler, and I. Fischer. 2001. Grafts of BDNF-producing fibroblasts that promote regeneration of axotomized rubrospinal neurons also rescue most neurons from retrograde death and prevent their atrophy. Exp. Neurol. (submitted).
Iwakawa, M., K. Mizoi, A. Tessler, and Y. Itoh. 2001. Intraspinal implants of fibrin glue containing glial cell line-derived neurotrophic factor promote dorsal root regeneration into spinal cord. Neurorehab. Neural Repair 15: 173-182. (abstract)
Kim, D., T. Schallert, Y.Liu, T. Browarak, N. Nayeri, A. Tessler, I. Fischer, and M. Murray 2001. Transplantation of genetically modified fibroblasts expressing BDNF in adult rats with a subtotal hemisection improves some motor functions. Neurorehab. Neural Repair 15: 141-150.
Jin, Y., I. Fischer, A. Tessler and J.D. Houle. 2002. Transplants of fibroblasts genetically modified to express BDNF promote axonal regeneration from supraspinal neurons following chronic spinal cord injury. Exp. Neurol. 177: 265-275. (abstract)
Murray, M., D. Kim, Y. Liu, C. Tobias, A. Tessler, and I. Fischer 2002. Transplantation of genetically modified cells contributes to repair and recovery from spinal injury. Brain Res. Rev. 40: 292-300. (abstract)
Liu, Y., B.T. Himes, M. Murray, A. Tessler, and I. Fischer. 2002. Grafts of BDNF-producing fibroblasts that promote regeneration of axotomized rubrospinal neurons also rescue most neurons from retrograde death and prevent their atrophy. Exp. Neurol. 178: 150-164.
Burns AS, B.S. Lee, J.F. Ditunno, A. Tessler 2003. Patient selection for clinical trials: the reliability of the early spinal cord injury examination. J. Neurotrauma 20(5):477-482. (abstract)
Houle J.D., A. Tessler. 2003. Repair of chronic spinal cord injury. Exp. Neurol. 182:247-260. (abstract)
Schwartz, E.D., J.S. Shumsky, S. Wehrli, A. Tessler, M. Murray and D.B. Hackney. 2003. Ex vivo MR apparent diffusion coefficients correlate with motor recovery mediated by intraspinal transplants of fibroblasts genetically modified to express BDNF. Exp. Neurol. 182:49-63. (abstract)
Tobias, C.A., J.S. Shumsky, M. Shibata, M.H. Tuszynski, I. Fischer, A. Tessler, M. Murray. 2003. Delayed grafting of BDNF and NT-3-expressing fibroblasts into the injured spinal cord stimulates sprouting, partially rescues axotomized red nucleus neurons from loss and atrophy and provides limited regeneration. Exp. Neurol. 184:97-113. (abstract)
Ditunno, J.F., J.W. Little, A.S. Burns, A. Tessler. 2004. Spinal shock revisited: a four phase model. Spinal Cord 42:383-395. (abstract)
Murray, M., I. Fischer, C. Smeraski, A. Tessler, S. Giszter. 2004. Towards a definition of recovery of function. J. Neurotrauma 21:405-413. (abstract)
Hayashi, Y., J.S. Shumsky, T. Connors, T. Otsuka, I. Fischer, A. Tessler, M. Murray. 2005. Immunosuppression with either cyclosporine A or FK506 promotes repair processes after spinal cord injury. J. Neurotrauma. Submitted for publication.
Burns, A.S., M.A. Lemay, and A. Tessler. (2005) Spontaneous potentials in distal muscles in animal models of spinal cord injury. Muscle and Nerve 31:46-51. (abstract)
Schwartz, E.D., C.L. Chin, J.S. Shumsky, A.F. Jawad, B.K. Brown, S. Wehrli, A. Tessler, M. Murray and D.B. Hackney. (2005). Apparent diffusion coefficients in spinal cord transplants and surrounding white matter correlate with degree of axonal dieback after injury in rats. Am. J. Neuroradiol. 26 (1): 7-18. (abstract)
Schwartz, E.D., E.T. Cooper, C-L Chin, S. Wehrli, A. Tessler, and D.B. Hackney. (2005) Ex vivo evaluation of ADC values within spinal cord white matter tracts. Am. J. Neuroradiol. 26 (2): 390-397. (abstract)
Li, P., A. Tessler, S.S.W. Han, I. Fischer, M. S. Rao, and M.E. Selzer. (2005) Fate of immortalized human neuronal progenitor cells transplanted into rat spinal cord. Arch. Neurol. 62: 223-229. (abstract)
Tobias, C.A., S.S.W. Han, J.S. Shumsky, D . Kim, M. Tumulo, N.O Dhoot, M.A.
Wheatley, I. Fischer, A. Tessler and M. Murray. (2005) Alginate encapsulated
BDNF-producing fibroblast grafts permit recovery of function after spinal cord
injury in the absence of immune suppression. J. Neurotrauma. 22: 138-156.
Books and chapters in books (since 2000):
Saavedra, R. A., M. Murray, S. deLacalle and A. Tessler. 2000. In vivo neuroprotection of injured CNS neurons by a single injection of a DNA plasmid encoding the BCL-2 gene. Prog. Br. Res. 128: 365-372.
Liu, Y., M. Murray, A. Tessler and I. Fischer. 2000. Grafting of genetically modified fibroblasts into the injured spinal cord. Prog. Br. Res. 128: 309-319.
Himes, BT, and Tessler A. 2001. Neuroprotection from cell death following axotomy. In N.A. Ingoglia and M. Murray (eds.) Nerve Regeneration: New York: Marcel Dekker. pp. 477-504.
Selzer, ME, and Tessler A. 2000. Spinal cord regeneration. In E.G. Gonzalez, S.J. Myers, J.E. Edelstein, J.S. Lieberman and J.A. Downey (eds.) Downey and Darling’s Physiological Basis of Rehabilitation Medicine. 3rd Edition.: Woburn, MA. Pp. 629-662.
Ditunno, JF, AE Flanders, S Kirshblum, V Graziani and A Tessler 2002. Predicting outcome in traumatic spinal cord injury. In: S Kirshblum, DI Campagnolo and JA DeLisa (Eds.) Spinal Cord Medicine. Philadelphia: Lippincott Williams & Wilkins, pp. 108-122.
Tessler. A. 2004. Neurotrophic effects on dorsal root regeneration into the spinal cord. In: S. Mori, D.G. Stuart and M. Wiesendanger (Eds.), Brain Mechanisms for the Integration of Posture and Movement, Prog. Br. Res. Vol. 000, Amsterdam: Elsevier, pp. 147-154.
Fischer, I, AC Lepore, SSW Han and A Tessler. (2005) Cellular replacement in
spinal cord injury. In: ME Selzer, S Clarke, LG Cohen, PW Duncan and FH Gage
(Eds.) Textbook of Neural Repair and Rehabilitation. Cambridge: Cambridge