Hyperphosphorylated neurofilament NF-H as a biomarker of the efficacy of minocycline therapy for spinal cord injury

Spinal Cord. 2011 Mar;49(3):333-6. doi: 10.1038/sc.2010.116. Epub 2010 Aug 31.

Abstract

Study design: An in vivo study in a rat model of acute spinal cord contusion.

Objectives: To assess the efficacy of novel therapies for acute spinal cord injury (SCI), methods to evaluate accurately the effects of these therapies should be developed. Although neurological examination is commonly used for this purpose, unstable clinical conditions and the spontaneous recovery of neurological function in the acute and subacute phases after injury make this measurement unreliable. Recent studies have reported that the phosphorylated form of the high-molecular-weight neurofilament subunit NF-H (pNF-H), a new biomarker for axonal degeneration, can be measured in serum samples in experimental SCI animals. Therefore, we aimed to investigate the use of plasma pNF-H as an indicator of the efficacy of minocycline, a neuroprotective drug, for treating SCI.

Setting: This study was carried out at Saitama, Japan.

Methods: Spinal cord injured rats received either minocycline or saline intraperitoneally. The plasma pNF-H levels and functional hind limb score were determined after the injury.

Results: Minocycline treatment reduced plasma pNF-H levels at 3 and 4 days post-injury (dpi). Rats with lower plasma pNF-H levels at 3 dpi had higher hind limb motor score at 28 dpi.

Conclusions: pNF-H levels may serve as a biomarker for evaluating the efficacy of therapies for SCI.

MeSH terms

  • Animals
  • Biomarkers / blood
  • Disease Models, Animal
  • Minocycline / pharmacology
  • Minocycline / therapeutic use*
  • Neurofilament Proteins / blood*
  • Neuroprotective Agents / therapeutic use*
  • Phosphorylation / drug effects
  • Phosphorylation / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects
  • Recovery of Function / physiology
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / physiopathology

Substances

  • Biomarkers
  • Neurofilament Proteins
  • Neuroprotective Agents
  • neurofilament protein H
  • Minocycline