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

•The efficacy of galantamine for hypoxic-ischemic brain damage was evaluated in newborn rats.•Single dose of 5.0 mg/kg galantamine showed a marked reduction of brain damage.•Microglial accumulation and IL-1β production was significantly reduced with 5.0 mg/kg of galantamine.

AimOur aim is to elucidate whether galantamine, known as an acetylcholinesterase inhibitor, reduces brain damage induced by hypoxia-ischemia (HI).Study design7-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; 1.0 mg/kg, n = 11) and after hypoxia (5.0 mg/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.ResultsTwo of the 5.0 mg/kg galantamine pre-treated rats and a post-treated rat died during experiments. The remaining survived and 5.0 mg/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).ConclusionPre-treatment of galantamine reduced brain damage with a suppressive effect on microglial accumulation and IL-1β production in a newborn rat model of HI.