title: Galantamine, an acetylcholinesterase inhibitor, reduces brain damage induced by hypoxia-ischemia in newborn rats.
abstract: OBJECTIVE
  Our aim is to elucidate whether galantamine, known as an acetylcholinesterase inhibitor, reduces brain damage induced by hypoxia-ischemia (HI).
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Obstetrics & Gynecology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. Electronic address: shiiba46seishi@gmail.com.
authors: Seishi
authors: S
authors: Furukawa
authors: Department of Obstetrics & Gynecology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors: Li
authors: L
authors: Yang
authors: Department of Obstetrics & Gynecology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors: Hiroshi
authors: H
authors: Sameshima
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005702:Galantamine / Q000627:therapeutic use*; D020925:Hypoxia-Ischemia, Brain / Q000150:complications*; D053583:Interleukin-1beta / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D051381:Rats
chemical_list: D002800:Cholinesterase Inhibitors; D053583:Interleukin-1beta; D005702:Galantamine
keywords: Acetylcholine; Hypoxia-ischemia; Microglia; Perinatal; Perinatal brain injury; Rat