The role of trapidil on neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury

Early Hum Dev. 2008 Apr;84(4):243-7. doi: 10.1016/j.earlhumdev.2007.06.005. Epub 2007 Aug 13.

Abstract

Background: Hypoxic ischemic brain injury (HIBI) is a common cause of neonatal mortality and morbidity. Trapidil is an antiplatelet agent and several studies demonstrate the beneficial effect of trapidil in various forms of tissue injury. The effects of trapidil on neuronal apoptosis in HIBI have not been reported previously.

Aims: The aim of this study is to evaluate the effect of trapidil on neuronal apoptosis in neonatal rat model of HIBI.

Study design: Seven-day-old Wistar rat pups were subjected to right common carotid artery ligation and hypoxia (92% nitrogen and 8% oxygen) for 2h. They were treated with trapidil or saline either immediately before or after hypoxia. In sham group animals, neither ligation, nor hypoxia were performed. Neuronal apoptosis was evaluated by the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) and caspase-3 staining methods.

Results: Trapidil treatment either before or after hypoxia results in significant reduction of the numbers of apoptotic cells in both hemispheres, when it is compared with saline treatment group. The numbers of apoptotic cells in right hemispheres in all groups are significantly higher than that in the left hemispheres.

Conclusions: These results show that trapidil administration either before or after hypoxia reduces neuronal apoptosis and we propose that trapidil may be a novel approach for the therapy of HIBI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Caspase 3 / metabolism
  • Cell Count
  • Disease Models, Animal
  • Female
  • Hypoxia-Ischemia, Brain / drug therapy*
  • Hypoxia-Ischemia, Brain / enzymology
  • Hypoxia-Ischemia, Brain / pathology
  • Male
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / enzymology
  • Rats
  • Rats, Wistar
  • Trapidil / administration & dosage*
  • Trapidil / therapeutic use
  • Vasodilator Agents / administration & dosage*
  • Vasodilator Agents / therapeutic use

Substances

  • Vasodilator Agents
  • Caspase 3
  • Trapidil