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Galantamine, an acetylcholinesterase inhibitor, reduces brain damage induced by hypoxia‐ischemia in newborn rats
Author(s) -
Furukawa Seishi,
Yang Li,
Sameshima Hiroshi
Publication year - 2014
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2014.06.011
Subject(s) - galantamine , neuroprotection , acetylcholinesterase , hypoxia (environmental) , acetylcholinesterase inhibitor , ischemia , endocrinology , saline , brain damage , medicine , hippocampus , pharmacology , chemistry , enzyme , biochemistry , oxygen , donepezil , dementia , disease , organic chemistry
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; 1.0 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. Results Two of the 5.0 mg/kg galantamine pre‐treated rats and a post‐treated rat died during experiments. The remaining survived and 5.0 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). 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.