Effects of neotrofin on neonatal hypoxic ischemic brain injury

Neurosci Lett. 2011 Nov 14;505(2):205-10. doi: 10.1016/j.neulet.2011.10.027. Epub 2011 Oct 19.


Hypoxia-ischemia is a major cause of perinatal brain injury in the newborn. Neotrofin, a neurotrophin agonist, has been shown to provide neuroprotection in several in vivo and in vitro studies. The aim of this study is to investigate the neuroprotective and ameliorating effects of neotrofin treatment after hypoxic-ischemic-injury-induced neuronal cell death, apoptosis in a neonatal hypoxic-ischemic brain injury rat model. Twenty-one seven-day-old Wistar rat pups were used in this study. The groups were: (1) a neotrofin-treated hypoxic-ischemic-group, (2) a saline-treated hypoxic-ischemic-group, and (3) a sham-operated group. Rat pups were subjected to left carotid artery occlusion followed by 2.5h of hypoxic exposure. After the hypoxic exposure, group one received an intra-peritoneal injection of neotrofin at a dose of 60mg/kg. Forty-eight hours after hypoxia, the animals were killed for histopathological evaluation to detect apoptosis and density of neurons. We found that neotrofin attenuates hypoxia-ischemia induced with neuronal density of the hippocampus, the prefrontal and the parietal cortex, and decreased apoptotic cell index in the same regions. Given our results, neotrofin may be useful in reducing brain injury; it possesses clinical relevance for the treatment of hypoxic-ischemic encephalopathy in the newborn.

MeSH terms

  • Aminobenzoates / pharmacology*
  • Aminobenzoates / therapeutic use
  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Disease Models, Animal
  • Female
  • Fetal Hypoxia / pathology
  • Fetal Hypoxia / physiopathology
  • Fetal Hypoxia / prevention & control*
  • Hypoxanthines / pharmacology*
  • Hypoxanthines / therapeutic use
  • Hypoxia-Ischemia, Brain / pathology
  • Hypoxia-Ischemia, Brain / physiopathology
  • Hypoxia-Ischemia, Brain / prevention & control*
  • Male
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Nerve Degeneration / prevention & control
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Rats
  • Rats, Wistar


  • Aminobenzoates
  • Hypoxanthines
  • Neuroprotective Agents
  • 4-((3-(1,6-dihyro-6-oxo-9H-purin-9-yl)-1-oxopropyl)amino)benzoic acid