RECOVERY OF FUNCTION AFTER SPINAL CORD DAMAGE

Summary

Principal Investigator: M Murray
Affiliation: Drexel University
Country: USA
Abstract: DESCRIPTION (provided by applicant) This Program Project focuses on strategies for repair of spinal cord injury, assessment of function and development of methods to improve outcome after spinal injury. During the previous funding period we developed cellular and molecular modifications of grafting strategies that will rescue injured neurons and promote regeneration and that are associated with recovery of function. We have also exploited pharmacological interventions that can further enhance function. In addition, we have developed functional analyses of deficits and recovery that provide methods to identify the mechanisms underlying the function that recovers. We build on these findings in the present application with an emphasis on physiological analysis for better assessment of recovery. In one Project we will use fibroblasts modified to express neurotrophic factors to stimulate regeneration of supraspinal axons after acute and chronic spinal hemisections and transections in adult rats. In another Project we will explore the use of genetically modified neural stem cells, a grafting strategy that offers the possibility of replacement of lost neurons, to promote spinal repair, regeneration in adult rats. One Project will continue to identify pharmacological interventions that can act synergistically with the grafts to improve function in animals operated as neonates and as adults. Two Projects are concerned with biomechanical and physiological assessment of function. The goal in one Project is to identify critical interactions between motor cortex and spinal cord that are required for recovery after transections in neonates and adults and to determine whether fetal grafts or grafting strategies developed in two Projects and pharmacological strategies developed in another Project will modify cortical and spinal organization. One Project investigates functional changes in sensorimotor cortex and red nucleus after spinal injury, and after application of transplantation strategies developed in two Projects and pharmacological strategies developed in another Project. Animals in all projects are evaluated in the Behavior Core using a standard set of behavioral measures. This allows direct comparison of functional outcome of grafting strategies. Overall, this Program Project emphasizes the integration of new experimental strategies that promote rescue and regeneration with detailed functional analysis comprised of behavioral, pharmacological, and physiological tests that assess recovery, suggest mechanisms and may ultimately provide neuroprosthetic alternatives.
Funding Period: 1987-04-01 - 2008-06-30
more information: NIH RePORT

Top Publications

  1. pmc How spinalized rats can walk: biomechanics, cortex, and hindlimb muscle scaling--implications for rehabilitation
    Simon F Giszter
    Neurobiology and Anatomy, School of Bioengineering, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA
    Ann N Y Acad Sci 1198:279-93. 2010
  2. ncbi Neurotrophic factors promote and enhance locomotor recovery in untrained spinalized cats
    Vanessa S Boyce
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA
    J Neurophysiol 98:1988-96. 2007
  3. ncbi Sensorimotor deficits associated with brain tumor progression and tumor-induced brain plasticity mechanisms
    Hongyan Yang
    Institute for Neuroscience and Department of Psychology, University of Texas at Austin, 1 University Station, A8000, Austin, TX 78712, USA
    Exp Neurol 207:357-67. 2007
  4. pmc Rat motoneuron properties recover following reinnervation in the absence of muscle activity and evoked acetylcholine release
    Edyta K Bichler
    Department of Physiology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA
    J Physiol 585:47-56. 2007
  5. pmc Robot application of elastic fields to the pelvis of the spinal transected rat: a tool for detailed assessment and rehabilitation
    Ubong I Udoekwere
    Sch of Bioeng, Drexel Univ, Philadelphia, PA, USA
    Conf Proc IEEE Eng Med Biol Soc 1:3684-7. 2006
  6. pmc Nogo-66 receptor antagonist peptide (NEP1-40) administration promotes functional recovery and axonal growth after lateral funiculus injury in the adult rat
    Y Cao
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA
    Neurorehabil Neural Repair 22:262-78. 2008
  7. pmc Spinal cord injury: present and future therapeutic devices and prostheses
    Simon F Giszter
    Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA
    Neurotherapeutics 5:147-62. 2008
  8. pmc Trunk sensorimotor cortex is essential for autonomous weight-supported locomotion in adult rats spinalized as P1/P2 neonates
    Simon Giszter
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA
    J Neurophysiol 100:839-51. 2008
  9. pmc Coordination strategies for limb forces during weight-bearing locomotion in normal rats, and in rats spinalized as neonates
    Simon F Giszter
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA
    Exp Brain Res 190:53-69. 2008
  10. ncbi Stem cell delivery by lumbar puncture as a therapeutic alternative to direct injection into injured spinal cord
    Birgit Neuhuber
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA
    J Neurosurg Spine 9:390-9. 2008

Scientific Experts

  • MICHELLE RENEE CIUCCI
  • K A Moxon
  • Robert D Flint
  • Hongyan Yang
  • Simon F Giszter
  • A C Lepore
  • Vanessa S Boyce
  • Xuepeng Zhang
  • Feng Jiang
  • Timothy Schallert
  • Michael Chopp
  • Tina Kao
  • Marion Murray
  • Jed S Shumsky
  • Anthony S Burns
  • B Timothy Himes
  • Arun Ramakrishnan
  • Michelle R Davies
  • Michel A Lemay
  • Birgit Neuhuber
  • Guglielmo Foffani
  • Itzhak Fischer
  • M S Rao
  • I Fischer
  • Y Hayashi
  • M Murray
  • Ubong Ime Udoekwere
  • J S Shumsky
  • Simon Giszter
  • Y Cao
  • Virginia Graziani
  • John K Chapin
  • Raymond Hermer-Vazquez
  • Edyta K Bichler
  • Alan Tessler
  • Banu Tutunculer
  • S S W Han
  • M P Daniels
  • Y Liu
  • B Neuhuber
  • T M Connors
  • Ubong I Udoekwere
  • R Olexa
  • S McBride
  • S Jacob-Vadakot
  • Greg Hockensmith
  • E A Dugan
  • K Simansky
  • Takahiko Mitsui
  • S A Rabacchi
  • Alissa L Barshinger
  • S Strittmatter
  • William J Kargo
  • F P T Hamers
  • Courtney Paul
  • D H S Lee
  • M A Sabol
  • R A Kushner
  • Sridhar Srinivasan
  • Martin J Pinter
  • Zhenggang Zhang
  • Barbara Weiland
  • Maureen Tumolo
  • Mark M Rich
  • Young Jin Son
  • Timothy C Cope
  • Dario I Carrasco
  • Sabiha Jawaid
  • Steve Kalkanis
  • Hui Zhong
  • Hiroyuki Yoshihara
  • Roland R Roy
  • Norman Tepley
  • Linda Hermer-Vazquez
  • Srishti Bhagat
  • Carl Coleman
  • Lollise Mbi
  • Stacy Jacob-Vadakot
  • Joseph Wagner
  • Sharon A Swanger
  • Robert Kushner
  • J W M Bulte
  • Gene C Kopen
  • Marnie Preston
  • P Walczak

Detail Information

Publications31

  1. pmc How spinalized rats can walk: biomechanics, cortex, and hindlimb muscle scaling--implications for rehabilitation
    Simon F Giszter
    Neurobiology and Anatomy, School of Bioengineering, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA
    Ann N Y Acad Sci 1198:279-93. 2010
    ..Pattern generation may be built into the lumbar spinal cord by evolution and matched to the limb biomechanics, so preserved muscle scaling may be essential to the NST function observed...
  2. ncbi Neurotrophic factors promote and enhance locomotor recovery in untrained spinalized cats
    Vanessa S Boyce
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA
    J Neurophysiol 98:1988-96. 2007
    ..Finally, the results show that transplants beneficial in rodents are applicable to larger mammals...
  3. ncbi Sensorimotor deficits associated with brain tumor progression and tumor-induced brain plasticity mechanisms
    Hongyan Yang
    Institute for Neuroscience and Department of Psychology, University of Texas at Austin, 1 University Station, A8000, Austin, TX 78712, USA
    Exp Neurol 207:357-67. 2007
    ....
  4. pmc Rat motoneuron properties recover following reinnervation in the absence of muscle activity and evoked acetylcholine release
    Edyta K Bichler
    Department of Physiology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA
    J Physiol 585:47-56. 2007
    ..Our results indicate that spontaneous release of acetylcholine from regenerated motor terminals is sufficient to operate the system...
  5. pmc Robot application of elastic fields to the pelvis of the spinal transected rat: a tool for detailed assessment and rehabilitation
    Ubong I Udoekwere
    Sch of Bioeng, Drexel Univ, Philadelphia, PA, USA
    Conf Proc IEEE Eng Med Biol Soc 1:3684-7. 2006
    ..Our system provides an animal model of rehabilitation through robot interaction at the pelvis...
  6. pmc Nogo-66 receptor antagonist peptide (NEP1-40) administration promotes functional recovery and axonal growth after lateral funiculus injury in the adult rat
    Y Cao
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA
    Neurorehabil Neural Repair 22:262-78. 2008
    ..The authors used a similar design to examine recovery and repair after a lesion that interrupts the rubrospinal tract (RST)...
  7. pmc Spinal cord injury: present and future therapeutic devices and prostheses
    Simon F Giszter
    Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA
    Neurotherapeutics 5:147-62. 2008
    ....
  8. pmc Trunk sensorimotor cortex is essential for autonomous weight-supported locomotion in adult rats spinalized as P1/P2 neonates
    Simon Giszter
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA
    J Neurophysiol 100:839-51. 2008
    ..Our data show that effective cortical mechanisms for trunk control are essential for autonomous weight support in P1/P2 spinalized rats and these can be achieved by intrinsic plasticity...
  9. pmc Coordination strategies for limb forces during weight-bearing locomotion in normal rats, and in rats spinalized as neonates
    Simon F Giszter
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA
    Exp Brain Res 190:53-69. 2008
    ..Because forelimbs and hind-limbs acted in opposition, the trunk was held compressed. Force coordination was likely managed largely by the voluntary control in forelimbs and trunk...
  10. ncbi Stem cell delivery by lumbar puncture as a therapeutic alternative to direct injection into injured spinal cord
    Birgit Neuhuber
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA
    J Neurosurg Spine 9:390-9. 2008
    ..To avoid additional trauma and to simplify translation to the clinic, it is advantageous to use less invasive delivery methods...
  11. pmc Modularity of endpoint force patterns evoked using intraspinal microstimulation in treadmill trained and/or neurotrophin-treated chronic spinal cats
    Vanessa S Boyce
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia PA 19129, USA
    J Neurophysiol 101:1309-20. 2009
    ..EMG analysis demonstrated that muscle activity highly predicted some force pattern types and was independent of hindlimb position. We conclude that spinal motor output modularity is preserved after injury...
  12. ncbi Using behavioral measurement to assess tumor progression and functional outcome after antiangiogenic treatment in mouse glioma models
    Hongyan Yang
    Institute for Neuroscience, Department of Psychology, University of Texas at Austin, Austin, TX 78712, USA
    Behav Brain Res 182:42-50. 2007
    ....
  13. pmc Motor strategies used by rats spinalized at birth to maintain stance in response to imposed perturbations
    Simon F Giszter
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA
    J Neurophysiol 97:2663-75. 2007
    ..The stance strategy of the P1 spinalized rats differed strongly from the behavior of intact rats and may be difficult for rats spinalized as adults to master...
  14. ncbi Mass-related traumatic tissue displacement and behavior: a screen for treatments that reduce [corrected] harm to bystander cells and recovery of function
    Hongyan Yang
    Institute for Neuroscience and Department of Psychology, University of Texas at Austin, Austin, Texas 78712, USA
    J Neurotrauma 23:721-32. 2006
    ..This model may permit development of treatment strategies to alleviate brain mass effects, without disrupting neuroplasticity...
  15. ncbi Long-term fate of neural precursor cells following transplantation into developing and adult CNS
    A C Lepore
    Department of Neurobiology and Anatomy, 2900 Queen Lane, Drexel University College of Medicine, Philadelphia, PA 19129, USA
    Neuroscience 139:513-30. 2006
    ....
  16. ncbi Recovery of function following grafting of human bone marrow-derived stromal cells into the injured spinal cord
    B Timothy Himes
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA
    Neurorehabil Neural Repair 20:278-96. 2006
    ..However, the use of carefully characterized BMSCs improved transplantation protocols ensuring BMSC, survival, and systematic motor and sensory behavioral testing to identify robust recovery is imperative for further improvement...
  17. ncbi Local fluorouracil chemotherapy interferes with neural and behavioral recovery after brain tumor-like mass compression
    Hongyan Yang
    Institute for Neuroscience, University of Texas at Austin, 1 University Station, Austin, TX 78712, USA
    Behav Brain Res 172:80-9. 2006
    ....
  18. ncbi MR imaging of lineage-restricted neural precursors following transplantation into the adult spinal cord
    A C Lepore
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA
    Exp Neurol 201:49-59. 2006
    ..The present results are relevant for MR-guided clinical application of transplantation strategies in treatment of spinal cord injury and other CNS pathologies...
  19. ncbi Role of the 5-HT2C receptor in improving weight-supported stepping in adult rats spinalized as neonates
    Tina Kao
    Drexel University College of Medicine, Philadelphia, PA 19129, USA
    Brain Res 1112:159-68. 2006
    ..Since mCPP does not have the behavioral toxicity associated with non-selective 5-HT2 receptor agonists, targeting the 5-HT2C receptor may have clinical relevance for the treatment of SCI...
  20. ncbi Paralysis elicited by spinal cord injury evokes selective disassembly of neuromuscular synapses with and without terminal sprouting in ankle flexors of the adult rat
    Anthony S Burns
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA
    J Comp Neurol 500:116-33. 2007
    ....
  21. ncbi Long-term fate of neural precursor cells following transplantation into developing and adult CNS
    A C Lepore
    Department of Neurobiology and Anatomy, 2900 Queen Lane, Drexel University College of Medicine, Philadelphia, PA 19129, USA
    Neuroscience 142:287-304. 2006
    ....
  22. ncbi Fibrillation potentials following spinal cord injury: improvement with neurotrophins and exercise
    Anthony S Burns
    Department of Rehabilitation Medicine, Thomas Jefferson University, 132 S 10th Street, 375 Main Building, Philadelphia, Pennsylvania 19107, USA
    Muscle Nerve 35:607-13. 2007
    ..These findings suggest that neurotrophins and activity play an important role in the poorly understood phenomenon of fibrillations distal to SCI...
  23. ncbi Interruption of functional recovery by the NMDA glutamate antagonist MK801 after compression of the sensorimotor cortex: implications for treatment of tumors or other mass-related brain injuries
    Hongyan Yang
    Institute for Neuroscience and Department of Psychology, University of Texas at Austin, 1 University Station, A8000, Austin, TX 78712, USA
    Exp Neurol 200:262-6. 2006
    ..It may be possible to use this model to develop interventions that maintain anti-cancer effects but with diminished harm to bystander tissue and brain plasticity...
  24. pmc 5-HT precursor loading, but not 5-HT receptor agonists, increases motor function after spinal cord contusion in adult rats
    Y Hayashi
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA
    Exp Neurol 221:68-78. 2010
    ..While no side effects were observed in normal or MOD rats, SEV rats displayed hindlimb tremors and 33% mortality, indicating hypersensitivity to the precursor...
  25. pmc Reduction of dopamine synaptic activity: degradation of 50-kHz ultrasonic vocalization in rats
    Michelle R Ciucci
    Department of Psychology, University of Texas at Austin, USA
    Behav Neurosci 123:328-36. 2009
    ..Our findings suggest that the nigrostriatal dopamine pathway is involved to some extent in fine sensorimotor function that includes USV production and complexity...
  26. pmc Exercise induces cortical plasticity after neonatal spinal cord injury in the rat
    Tina Kao
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA
    J Neurosci 29:7549-57. 2009
    ..Therefore, the increase in responsiveness of hindlimb SI to forelimb stimulation after neonatal transection and exercise may be due, in part, to the effect of exercise on the forelimb SI...
  27. doi Responses of infragranular neurons in the rat primary somatosensory cortex to forepaw and hindpaw tactile stimuli
    K A Moxon
    School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA
    Neuroscience 156:1083-92. 2008
    ....
  28. pmc Beta- and gamma-frequency coupling between olfactory and motor brain regions prior to skilled, olfactory-driven reaching
    Raymond Hermer-Vazquez
    Behavioral Neuroscience Program, Department of Psychology, University of Florida, Gainesville, FL 32611, USA
    Exp Brain Res 180:217-35. 2007
    ..These results indicate that transient, multispectral coherence across cortical and subcortical brain sites is part of the coordination process prior to sensory-guided movement initiation...
  29. pmc Computational role of large receptive fields in the primary somatosensory cortex
    Guglielmo Foffani
    School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104, USA
    J Neurophysiol 100:268-80. 2008
    ....
  30. ncbi Towards a method to study neurorobotic control in a rat model of spinal cord injury
    Robert D Flint
    School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA 19104 USA
    Conf Proc IEEE Eng Med Biol Soc . 2006
    ..The method provides a means by which changes in neural activation can be correlated with changes in behavior...
  31. ncbi Structure of the excitatory receptive fields of infragranular forelimb neurons in the rat primary somatosensory cortex responding to touch
    Banu Tutunculer
    School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA
    Cereb Cortex 16:791-810. 2006
    ..This highly distributed receptive field structure provides the electrophysiological architecture for studying organization and plasticity of cortical somatosensory processing...