Transplants of nerve growth promoting factors into the injured spinal cord promote the recovery of locomotion in animal models of spinal cord injury. We suspect that this recovery may be mostly due to the effects of those factors on the spinal cord circuitry responsible for the treadmill entrained locomotion that can be observed in spinalized animals and humans. Our long-term goals are to maximize the locomotor recovery obtainable after spinal cord injury using combination therapies combining regenerative grafts, sensorimotor training, and electrical stimulation of the lumbar locomotor circuitry.
The aims of this project are to establish: 1) whether growth from supraspinal centers is necessary to obtain the locomotor recovery provided by transplant of the growth factors, 2) whether the lumbar circuitry of locomotion can be activated by transplants in a sub-chronic or chronic model of injury, and 3) whether the effects of spinal transplants on the locomotor circuitry are similar in their actions to the effects obtained with locomotor training.
In Aims 1 &2, the locomotor recovery provided by the transplant of neurotrophins producing cells will be evaluated via kinematic analyses of treadmill locomotion in a mammalian model of spinal cord injury, and nerve growth will be measured using histological methods.
Aim 1 will use an impermeable membrane to block the possibility of supraspinal axonal growth through the injury.
In Aim 2, grafting will occur after a delay of 2 or 6 weeks following the spinal transection.
In Aim 3, the modifications to the spinal circuitry will be evaluated via stimulation of selected afferent pathways in groups of animals receiving the neurotrophins producing transplants or locomotor training, and using a recently introduced computational model of the mammalian locomotor neural circuitry combined with a musculo-skeletal model of the hindlimbs. The results of this project will provide significant insight into the spinal mechanisms responsible for the control of locomotion and will constitute an important step towards the development of effective methods for the restoration of locomotor function after spinal cord injury.
|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