Neuropharmacology

Biography

Biography: Elzbieta Salinska

Abstract

Perinatal hypoxia-ischemia is one of the main causes of brain injury in neonates. Hypothermia is the only intervention clinically available and thus the challenge to establish new effective therapies remain a priority in neuroscience. Promising results have been observed using individual treatments of memantine (uncompetitive NMDA receptor antagonist), hyperbaric oxygen (HBO) or mild hypobaric hypoxia (HH) postconditioning. As combination therapies become recently a chance for better results, we decided to investigate whether the combination of memantine (20 mg/kg) treatment with HBO (2.5 ATA) or HH (0.47 ATA) would act synergistically on brain injury evoked by experimental model of birth asphyxia. 7-day old rats were subjected to hypoxia-ischemia (H-I) and then treated either with memantine, HBO, HH or combination of these treatments, started 1h or 6 h after H-I, and repeated for two subsequent days. Application of memantine, HBO or HH resulted in reduction in brain weight deficit, the size of infarct area and apoptosis. Reduction of chosen parameters accompanying oxidative stress was also observed. However, combining memantine with HBO treatment or HH postconditioning resulted in a loss of neuroprotective effects. In conclusion, our results show that memantine, HBO and HH applied separately shortly after H-I do provide neuroprotection, whereas combining memantine with HBO or HH, does not result in additive increase in the neuroprotective effect; on the contrary, combining the treatments increased neurodegeneration. This may suggest that treatments used in our study either compete acting towards the same elements or have the antagonistic effect on the intracellular mechanisms of neuroprotection.