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  2. Forelimb motor recovery by modulating extrinsic and intrinsic signaling as well as neuronal activity after the cervical spinal cord injury

Forelimb motor recovery by modulating extrinsic and intrinsic signaling as well as neuronal activity after the cervical spinal cord injury

  • bioRxiv. 2024 Jun 27:2024.06.22.600167. doi: 10.1101/2024.06.22.600167.
Hirohide Takatani 1 2 3 Naoki Fujita 3 Fumiyasu Imai 1 2 Yutaka Yoshida 1 2 4 5
Affiliations

Affiliations

  • 1 Burke Neurological Institute, White Plains, New York, United States.
  • 2 Brain and Mind Research Institute, Weill Cornell Medicine, New York, United States.
  • 3 Laboratory of Veterinary Surgery, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
  • 4 Neural Circuit Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan.
  • 5 Lead contact.
Abstract

Singular strategies for promoting axon regeneration and motor recovery after spinal cord injury (SCI) have been attempted with limited success. Here, we propose the combinatorial approach of deleting extrinsic and intrinsic factors paired with neural stimulation, will enhance adaptive axonal growth and motor recovery after SCI. We previously showed the deletion of RhoA and PTEN in corticospinal neurons inhibits axon dieback and promotes axon sprouting after lumbar SCI. Here, we examined the effects of RhoA;Pten deletion coupled with neural stimulation after cervical SCI. This combinatorial approach promoted more boutons on injured corticospinal neurons in the spinal cord compared to sole RhoA;PTEN deletion. Although RhoA;PTEN deletion does not promote motor recovery in the forelimb after SCI, stimulating corticospinal neurons in those mice results in partial motor recovery. These results demonstrate that a combinatorial approach that pairs genetic modifications with neuronal stimulation can promote axon sprouting and motor recovery following SCI.

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