Intrathecal Administration of Flavopiridol Promotes Regeneration in Experimental Model of Spinal Cord Injury

Turk Neurosurg. 2016;26(6):922-929. doi: 10.5137/1019-5149.JTN.13745-15.2.

Abstract

Aim: Spinal cord injury (SCI) is a serious condition of the central nervous system and it affects the quality of life and even hampers the day-to-day activity of the patient. In the current study, we investigated the efficacy of intrathecal administration of flavopiridol in an experimental animal model of SCI. The study also aimed at exploring the physiological effects of flavopiridol on neurons, astrocytes and cell cycle regulatory proteins.

Material and methods: In vitro scratch wound experiments were performed on female Sprague-Dawley rats (n=23). A complete hemisection to the right of T10 was made, and flavopiridol solution (200 mM, 0.8 nmol flavopiridol/animal) was delivered topically to the lesion site. Cell viability assay, in vitro scratch injury assay, cell cycle analysis using flow cytometry and behavioural assessments were performed.

Results: The local delivery of flavopiridol reduced cavity formation and improved regeneration of neurons with improvement in physiological performance. Flavopiridol also inhibited the migration and proliferation of astrocytes, and at the same time, promoted the survival of neurons.

Conclusion: Intrathecal administration of flavopiridol can be a promising treatment strategy in patients with SCI and it needs to be validated in patient setting.

MeSH terms

  • Administration, Topical
  • Animals
  • Astrocytes / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Female
  • Flavonoids / administration & dosage*
  • Flavonoids / pharmacology*
  • Flavonoids / therapeutic use
  • Nerve Regeneration / drug effects*
  • Neurons / drug effects
  • Piperidines / administration & dosage*
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / pathology

Substances

  • Flavonoids
  • Piperidines
  • alvocidib