Delivery of neurotrophins to the spinal cord is a promising technique to re-engage the locomotor circuitry following spinal cord injury and their use may augment the recovery obtained with body-weight supported treadmill training. The mechanism by which neurotrophins promote locomotor recovery is unknown, but our modeling work suggests that plasticity in the afferent system transmission is involved in recovery.
Aim 1 will obtain information about the changes in afferent transmission to motoneurons and interneurons following neurotrophin delivery to the spinal cord and compare those to the ones obtained with body-weight supported treadmill training. Acquiring this information will provide new insights into the neural mechanisms associated with recovery after SCI and serve as a novel outcome measure for new therapies. We propose to use intracellular and multiunit recording techniques to characterize and compare the changes in afferent transmission obtained with body-weight supported treadmill training or neurotrophin producing cellular transplants. In addition, we will characterize the interneuronal activity patterns and afferent effects on this activity following to thetiA/otreatment modalities. We hypothesize that afferent transmission to motoneurons and interneurons is modified by neurotrophin transplants in a manner similar to the way it is affected by body-weight supported treadmill training, but that the effects are more widespread in the neurotrophin treated animals due to a wider distribution of the neurotrophins with this methodology. In our second aim, we intend to refine our transplant technique to the point where neurotrophin producing transplants could be attempted in the clinic with minimal risks for the patient. We hypothesize that neurotrophins can be delivered via lumbar puncture injection of autologous cells modified to express neurotrophins and that these cells will promote the recovery of plantar weight-bearing stepping without the need for training in acutely and chronically injured animals.

Public Health Relevance

The aims of this project are consistent with the NINDS'mission of reducing the burden of neurological diseases and will further our understanding of the mechanism by which neurotrophins promote locomotor recovery and establish the efficacy of a clinically translatable application of this treatment therapy.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Program Projects (P01)
Project #
Application #
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Drexel University
United States
Zip Code
Spruance, Victoria M; Zholudeva, Lyandysha V; Hormigo, Kristiina M et al. (2018) Integration of Transplanted Neural Precursors with the Injured Cervical Spinal Cord. J Neurotrauma 35:1781-1799
Zholudeva, Lyandysha V; Qiang, Liang; Marchenko, Vitaliy et al. (2018) The Neuroplastic and Therapeutic Potential of Spinal Interneurons in the Injured Spinal Cord. Trends Neurosci 41:625-639
Bezdudnaya, Tatiana; Hormigo, Kristiina M; Marchenko, Vitaliy et al. (2018) Spontaneous respiratory plasticity following unilateral high cervical spinal cord injury in behaving rats. Exp Neurol 305:56-65
Kar, Amar N; Lee, Seung Joon; Twiss, Jeffery L (2018) Expanding Axonal Transcriptome Brings New Functions for Axonally Synthesized Proteins in Health and Disease. Neuroscientist 24:111-129
Jin, Ying; Shumsky, Jed S; Fischer, Itzhak (2018) Axonal regeneration of different tracts following transplants of human glial restricted progenitors into the injured spinal cord in rats. Brain Res 1686:101-112
Zholudeva, Lyandysha V; Iyer, Nisha; Qiang, Liang et al. (2018) Transplantation of Neural Progenitors and V2a Interneurons after Spinal Cord Injury. J Neurotrauma 35:2883-2903
Chhaya, Soha J; Quiros-Molina, Daniel; Tamashiro-Orrego, Alessandra D et al. (2018) Exercise-Induced Changes to the Macrophage Response in the Dorsal Root Ganglia Prevent Neuropathic Pain after Spinal Cord Injury. J Neurotrauma :
Sahoo, Pabitra K; Smith, Deanna S; Perrone-Bizzozero, Nora et al. (2018) Axonal mRNA transport and translation at a glance. J Cell Sci 131:
Lane, Michael A; Lepore, Angelo C; Fischer, Itzhak (2017) Improving the therapeutic efficacy of neural progenitor cell transplantation following spinal cord injury. Expert Rev Neurother 17:433-440
Nair, Jayakrishnan; Bezdudnaya, Tatiana; Zholudeva, Lyandysha V et al. (2017) Histological identification of phrenic afferent projections to the spinal cord. Respir Physiol Neurobiol 236:57-68

Showing the most recent 10 out of 60 publications