Our laboratory at the University of Texas Medical Branch is currently investigating the mechanisms of recovery after spinal cord injury (SCI) using techniques that include molecular, pharmacological and cellular transplant approaches to determine the basis for recovery of motor function and the development of chronic pain.
An immediate goal in the treatment of SCI patients is the treatment of the pain syndromes that develop. We have developed a rodent model of SCI chronic pain and are investigating the outcomes of specific receptor antagonists toward inhibition of pain pathways at the molecular, electro-physiological and behavioral levels.
Another goal in SCI therapy is to provide a bridge of cellular tissue to replace the spinal cell populations that were injured and consequently died as a result of trauma. Such a bridge could also serve as a conduit for neurite growth across the gap created by the lesion. Toward this goal, we are characterizing cultured human fetal spinal neurons and are investigating the restorative potential of transplanting the cultured human fetal spinal cells into the grey matter of the rodent. The figure below shows the spinal neurons.

Human fetal spinal cord cells, grown in culture stained with DiI, a lipophilic stain. The nuclei of these cells are counterstained with Hoechst stain (white). Note the neurite-like processes extending several hundred millimeters and the growth cones at the terminus (top of figure)
Finally, in two models of brain injury, focal cortical ischemia and traumatic brain injury by fluid percussion, we are investigating the expression of neurotrophins and exogenous application of neurotrophins, by injections, infusions and transfection of cells with neurotrophin genes, to rescue neurons that would otherwise die due to brain trauma. A variety of experimental approaches are used in these studies including cell transfections, hybridizations, in situ hybridizations, immunocytochemistry, electrophysiology, electron microscopy, microdialysis and magnetic resonance imaging. As an important outcome measure, reliable behavioral tests of each neurotrauma model have been developed and are used to assess the success of interventions toward improved recovery of function following central nervous system trauma.
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Christensen, M.D. and Hulsebosch,
C.E. Chronic central pain after spinal cord injury. J.
Neurotrama 14: 517-537, 1997.
Hulsebosch, C.E.,
Xu, G-Y., Perez-Polo, J.R., Westlund, K.N., Taylor, C.P. and McAdoo, D.J.
Rodent model of chronic central pain after spinal cord contusion injury and
effects of gabapentin. J. Neurotrauma 17:1205-1217, 2000.
Hulsebosch, C.E., Hains,
B.C., Waldrep, K and Young, W. Bridging the gap: From discovery to
clinical trials in spinal cord injury. J. Neurotrauma 17:1117-1128, 2000.
Hains, B.C., Yucra, J.A.
and Hulsebosch, C.E. Reduction of pathological and behavioral
deficits following spinal cord contusion injury with the selective
cyclooxygenase-2 inhibitor NS-398. J. Neurotrauma 18:409-423, 2001.
Hains, B.C., Johnson, K.M., McAdoo, D.J., Eaton, M.J.
and Hulsebosch, C.E. Engraftment of serotonergic precursors
enhances locmotor function and attenuates chronic central pain behavior
following spinal hemisection injury in the rat. Exp. Neurol. 171:361-378,
2001.
Mills, C.D., Xu, G-y., McAdoo,
D.J. and Hulsebosch, C.E. Involvment of metabotropic glutamate
receptors in excitatory amino acid and GABA release following spinal cord injury
in rat. J. Neurochem. 79:835-848, 2001.
Qiu, J., Nesic, O., Ye, Z.,
Rea, H., Westlund, K.N., Xu, G-Y., McAdoo, D., Hulsebosch, C.E. and
Perez-Polo, J.R. Bcl-xL expression after contusion to the rat
spinal cord. J. Neurotrauma 18:1267-1278, 2001.
Mills, C.D., Johnson, K.M. and Hulsebosch,
C.E. Group I metabotropic glutamate receptors in spinal cord injury:
Roles in neuroprotection and the development of chronic central pain. J.
Neurotrauma 19:23-42, 2002.
Vera-Portocarrero, L.P., Mills,
C.D., Ye, Zaiming, Fullwood, S.D., McAdoo, D.J., Hulsebosch, C.E. and
Westlund, K.N. Rapid change4s in expression of glutamate transporters
after spinal cord injury. Brain Res. 927:104-110, 2002.
Mills, C.D. and Hulsebosch,
C.E. Increased expression of metabotropic glutamate receptor subtype 1
on spinothalamic tract neurons following spinal cord injury in the rat.
Neurosci. Lett. 319:59-62,2002.
Hains, B.C., Willis, W.D. and Hulsebosch,
C.E. Differential electrophysiological effects of brain-derived neurotrophic
factor on dorsal horn neurons following chronic spinal cord hemisection injury
in the rat. Neurosci. Lett. 320:125-128, 2002.
Nesic, O., Syrakic, N.M., Xu,
G-Y., McAdoo, D., Westlund, K.N., Hulsebosch, C.E., Ye, Z., Galante, A.,
Soteropoulos, P., Tolias, P., Young, W., Hart, R.P. and Perez-Polo, J.R.
DNA microarray analysis of the contused spinal cord: Effect of NMDA
receptor inhibition. J. Neurosci. Res. 68:406-423, 2002.
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