The functional and neuroprotective actions of Neu2000, a dual-acting pharmacological agent, in the treatment of acute spinal cord injury

Joe E. Springer, Ravikumar Rangaswamy Rao, Hyang Ran Lim, Sung Ig Cho, Gyoeng Joon Moon, Hee Young Lee, Eui Jin Park, Byoung Joo Gwag, Jai Sung Noh

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

The goal of the present study was to examine the neuroprotective and functional significance of targeting both N-methyl-d-aspartate (NMDA) receptor-mediated excitotoxicity and oxidative stress using a dual-acting compound, Neu2000, in rat model of moderate spinal cord injury (SCI). An initial set of experiments was conducted in uninjured rats to study the pharmacokinetic profile of Neu2000 following intraperitoneal and intravenous administration. A second experiment measured free radical production in mitochondria isolated from sham or injured spinal cords of animals receiving vehicle or Neu2000 treatment. A third set of animals was divided into three treatment groups consisting of vehicle treatment, a single dose of Neu2000 (50 mg/kg) administered at 10 min following injury, or a repeated treatment paradigm consisting of a single bolus of Neu2000 at 10 min following injury (50 mg/kg) plus a maintenance dose (25 mg/kg) administered every 24 h for an additional 6 days. Animals were tested once a week for a period of 6 weeks for evidence of locomotor recovery in an open field and kinematic analysis of fine motor control using the DigiGait Image Analysis System. At the end of the testing period, spinal cord reconstruction was performed to obtain nonbiased stereological measures of tissue sparing. The results of this study demonstrate that Neu2000 treatment significantly reduced the production of mitochondrial free radicals and improved locomotor outcomes that were associated with a significant increase in the volume of spared spinal cord tissue.

Original languageEnglish
Pages (from-to)139-149
Number of pages11
JournalJournal of Neurotrauma
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2010

Keywords

  • Excitotoxicity
  • Functional recovery
  • Oxidative stress
  • Spinal cord contusion
  • Tissue sparing

ASJC Scopus subject areas

  • Clinical Neurology

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