Combining hypobaric hypoxia or hyperbaric oxygen postconditioning with memantine reduces neuroprotection in 7-day-old rat hypoxia-ischemia

Abstract

Background: Perinatal hypoxia-ischemia causes brain injury in neonates, but a fully successful treatment to prevent changes in the brain has yet to be developed. The aim of this study was to evaluate the effect of combining memantine treatment with HBO (2.5 ATA) or HH (0.47 ATA) on neonatal hypoxia-ischemia brain injury.

Methods: 7-day old rats were subjected to hypoxia-ischemia (H-I) and treated with combination of memantine and HBO or HH. The brain damage was evaluated by examination of infarct area and the number of apoptotic cells in CA1 region of hippocampus. Additionally, the level of reactive oxygen species (ROS) was measured.

Results: Memantine, HBO or HH postconditioning applied at short time (1-6h) after H-I, and repeated for two subsequent days, resulted in significant neuroprotection. The reduction in ipsilateral hemisphere weight deficit and in the size of infarct area was observed 14days after H-I. A reduction in apoptosis and ROS level was also observed. Combining memantine with HBO or HH resulted in a loss of neuroprotection.

Conclusions: Our results show that, combining HBO or HH postconditioning with memantine produce no additive increase in the neuroprotective effect. On the contrary, combining the treatments resulted in lower neuroprotection in comparison to the effects of memantine, HBO or HH alone.

Keywords: Combination therapy; Hyperbaric oxygen; Hypoxia-ischemia; Memantine; Neuroprotection.