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

PubMedID: 24392823Objective: 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 2h. Sham group (n=8) had a median neck incision, but the rats were not subjected to ligation or hypoxia. The pups were treated with 20mg/kg/day caffeine citrate (n=8) or saline (n=8) immediately before HI and at 0, 24, 48 and 72h 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