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Continuous infusion of an agonist of the tumor necrosis factor receptor 2 in the spinal cord improves recovery after traumatic contusive injury.

  • Author(s): Gerald, Marcus J
  • Bracchi-Ricard, Valerie
  • Ricard, Jerome
  • Fischer, Roman
  • Nandakumar, Bharadwaj
  • Blumenthal, Gary H
  • Williams, Raushaun
  • Kontermann, Roland E
  • Pfizenmaier, Klaus
  • Moxon, Karen A
  • Bethea, John R
  • et al.

Published Web Location

https://doi.org/10.1111/cns.13125
Abstract

Aim

The activation of the TNFR2 receptor is beneficial in several pathologies of the central nervous system, and this study examines whether it can ameliorate the recovery process following spinal cord injury.

Methods

EHD2-sc-mTNFR2 , an agonist specific for TNFR2, was used to treat neurons exposed to high levels of glutamate in vitro. In vivo, it was infused directly to the spinal cord via osmotic pumps immediately after a contusion to the cord at the T9 level. Locomotion behavior was assessed for 6 weeks, and the tissue was analyzed (lesion size, RNA and protein expression, cell death) after injury. Somatosensory evoked potentials were also measured in response to hindlimb stimulation.

Results

The activation of TNFR2 protected neurons from glutamate-mediated excitotoxicity through the activation of phosphoinositide-3 kinase gamma in vitro and improved the locomotion of animals following spinal cord injury. The extent of the injury was not affected by infusing EHD2-sc-mTNFR2 , but higher levels of neurofilament H and 2', 3'-cyclic-nucleotide 3'-phosphodiesterase were observed 6 weeks after the injury. Finally, the activation of TNFR2 after injury increased the neural response recorded in the cortex following hindlimb stimulation.

Conclusion

The activation of TNFR2 in the spinal cord following contusive injury leads to enhanced locomotion and better cortical responses to hindlimb stimulation.

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