Effects of caffeine on neuronal apoptosis in neonatal hypoxic-ischemic brain injury

J Matern Fetal Neonatal Med. 2014 Sep;27(14):1470-5. doi: 10.3109/14767058.2013.878694. Epub 2014 Feb 11.

Abstract

Objective: Hypoxia-ischemia (HI) in rat pups leads to strong activation of apoptosis, and apoptosis contributes significantly to cerebral damage in the perinatal period. Caffeine displays a broad array of actions on the brain. The aim of this study was to investigate the effects of caffeine on neuronal apoptosis in a hypoxic-ischemic neonatal model.

Methods: Twenty-four seven-day-old Wistar rat pups were subjected to right common carotid artery ligation and hypoxia for 2 h. Sham group (n = 8) had a median neck incision, but the rats were not subjected to ligation or hypoxia. The pups were treated with 20 mg/kg/day caffeine citrate (n = 8) or saline (n = 8) immediately before HI and at 0, 24, 48 and 72 h post-hypoxia. Neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and caspase-3 in the hippocampus and parietal cortex of both hemispheres.

Results: The numbers of apoptotic cells in the hippocampus and parietal cortex were significantly higher in the saline group than they were in the sham group (p < 0.0001). The number of apoptotic cells in the hippocampus (p < 0.0001) and parietal cortex (p < 0.0001, TUNEL and p = 0.001, caspase-3) were higher in the caffeine-treated group than they were in the sham group, but the number of apoptotic cells decreased significantly in the caffeine-treated group compared with the saline group in the hippocampus (p < 0.0001, TUNEL and p = 0.001, caspase-3) and parietal cortex (p = 0.001, TUNEL and p = 0.002, caspase-3).

Conclusions: We show that caffeine administration in hypoxic-ischemic brain injury reduces neuronal apoptosis in the developing brain. We suggest that caffeine may be effective in reducing brain injury.

Keywords: Apoptosis; brain injury; caffeine; hypoxia; ischemia.

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects*
  • Brain / blood supply*
  • Brain / drug effects
  • Brain / pathology
  • Caffeine / administration & dosage*
  • Disease Models, Animal
  • Female
  • Hypoxia-Ischemia, Brain / drug therapy*
  • Hypoxia-Ischemia, Brain / pathology
  • Male
  • Neurons / drug effects*
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology
  • Organ Size / drug effects
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*

Substances

  • Neuroprotective Agents
  • Caffeine