EN
BACKGROUND AND AIMS: Perinatal hypoxia ischemia (HI) is a frequent cause of neonatal brain injury. The aim of present study was to investigate the effect of combining HBO or HH with memantine on HI evoked apoptosis and on Bcl-2, Bax and HIF-1α expression in hippocampus and cerebral cortex of the brains of neonatal rats. METHODS: HI on 7-day old rats was induced by ligation of ipsilateral common carotid artery, followed by 75 min hypoxia. HBO (2.5 ATA) or HH (0.5ATA) were applied 1 or 6 h after H-I for 60 min. Memantine in dose of 20 mg/kg of body weight was applied 15 minutes before HBO or HH. These treatments were repeated for 3 following days. Expression of Bcl-2, Bax and HIF-1α was examined using western blotting. RESULTS: In our study we showed that memantine and combined therapies reduced number of apoptotic cells in brains of treated animals. Memantine applied 1 or 6 h after HI increased Bcl-2 expression in the ipsilateral hemispheres by, respectively, 41 and 9%. Memantine combined with HBO 1 or 6 h after HI upregulated Bcl-2 by 13 and 21%, respectively, and memantine combined with HH postconditioning upregulated it by 42 and 29%. The preliminary results show that both memantine alone and combined therapies changed Bax expression in ipsilateral brain hemisphere comparing to untreated HI. Our study showed also that memantine and memantine combined with HBO or HH affected expression of HIF-1α which controls several genes that play a key role in neuroprotective processes. CONCLUSIONS: Our results show that application of memantine alone and in combination with HBO or HH reduce apoptotic processes initiated by HI in developing brain. However, the neuroprotection achieved by combined therapies is not significantly bigger than that resulted from memantine alone. This project was funded by the National Science Centre based on decision nr DEC 2012/07/N/NZ4/02072.