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

Authors
Springer, JE; Rao, RR; Lim, HR; Cho, SI; Moon, GJ; Lee, HY; Park, EJ; Noh, JS; Gwag, BJ
Citation
Journal of neurotrauma, 27(1):139-149, 2010
Journal Title
Journal of neurotrauma
ISSN
0897-71511557-9042
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.
MeSH terms
Acute DiseaseAnimalsAntioxidants/pharmacokinetics/therapeutic useBenzoic Acids/*pharmacokinetics/therapeutic useDisease Models, AnimalDrug Administration ScheduleFemaleFree Radicals/metabolismMitochondria/drug effects/metabolismMotor Activity/drug effects/physiologyNeuroprotective Agents/pharmacokinetics/therapeutic useNeurotoxins/antagonists & inhibitorsOxidative Stress/drug effects/physiologyRatsRats, Long-EvansRecovery of Function/drug effects/physiologySpinal Cord/drug effects/physiopathologySpinal Cord Injuries/*drug therapy/physiopathologyTreatment Outcome
DOI
10.1089/neu.2009.0952
PMID
19772458
Appears in Collections:
Journal Papers > Research Organization > Research Institute for Neural Science & Technology
Journal Papers > School of Medicine / Graduate School of Medicine > Psychiatry & Behavioural Sciences
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
조, 성익노, 재성곽, 병주
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