Galantamine, an acetylcholinesterase inhibitor, reduces brain damage induced by hypoxia‐ischemia in newborn rats

Abstract

AIM: Our aim is to elucidate whether galantamine, known as an acetylcholinesterase inhibitor, reduces brain damage induced by hypoxia-ischemia (HI). STUDY DESIGN: 7-day-old Wistar rats were used. Rats were subjected to left carotid artery ligation followed by 2 h of hypoxia (8% oxygen). We injected galantamine intraperitoneally just before hypoxia (5.0 mg/kg, n=14; 2.5 mg/kg, n=9; 1.0mg/kg, n=11) and after hypoxia (5.0mg/kg, n=7) to determine its neuroprotective effect. An equivalent volume of saline was administered as a control before (n=31) and after hypoxic load (n=7). We also examined the production of IL-1β in the ligated hemisphere side after injection of galantamine (prior hypoxia; 5.0 mg/kg, n=7) or saline (n=8). Brains were analyzed 7 days after HI. RESULTS: Two of the 5.0 mg/kg galantamine pre-treated rats and a post-treated rat died during experiments. The remaining survived and 5.0mg/kg galantamine pre-treated rats showed a marked reduction of brain damage (p<0.01) compared with the control. The other galantamine groups had severe brain damage similar to controls. Microglial accumulation was significantly reduced in rats pre-treated with 5.0 mg/kg of galantamine compared to control rats on both the hippocampus (p=0.02) and cortex (p<0.01). In contrast, the other galantamine groups showed a lower suppressive effect on microglial accumulation compared to the control. Galantamine significantly reduced IL-1β productions when compared to the control (p<0.01). CONCLUSION: Pre-treatment of galantamine reduced brain damage with a suppressive effect on microglial accumulation and IL-1β production in a newborn rat model of HI.