title: Regional differences of microglial accumulation within 72 hours of hypoxia-ischemia and the effect of acetylcholine receptor agonist on brain damage and microglial activation in newborn rats.
abstract: OBJECTIVE
  We examined regional specificity of microglial activation in the developing rat brain for 72 hours after hypoxia-ischemia (HI) and the effect of acetylcholine receptor (AChR) agonist on microglial activation.
  
  
  METHODS
  Seven-day-old Wistar rats were divided into two groups: one receiving a single dose of AChR agonist just before hypoxia (carbachol; 0.1mg/kg) to investigate the reducing effect on brain damage with decreasing activation of microglia and the other group receiving saline as a control. Rats were subjected to left carotid artery ligation followed by 8% hypoxia. Brains were analyzed immunohistochemically at 24, 48, and 72 hours after HI. TNFα production was measured at respective times after HI.
  
  
  RESULTS
  Activation of microglia on the hippocampus of the control group was strong for the first 48 hours and then weakened. In contrast, activation of microglia on white matter and the cortex was weak at 24 hours and then became stronger. A single dose of carbachol significantly reduced brain damage with a marked reduction of microglial activation on the hippocampus, whereas it was less effective regarding microglial activation on white matter and the cortex. TNFα production was low in both groups.
  
  
  CONCLUSIONS
  Regional specificity was observed for both microglial activation and susceptibility to carbachol for the first 72 hours after HI. Our data suggested that timely intervention along with region-specific microglial activation, apart from TNFα production, may be critical for the prevention of further brain damage after HI in the newborn.
authors.affiliation: Department of Obstetrics & Gynecology, Faculty of Medicine, University of Miyazaki, 5200 Kihara-Kiyotake, Miyazaki 892-1601, Japan. Electronic address: snhm10@fc.miyazaki-u.ac.jp.
authors.forename: Seishi
authors.initials: S
authors.lastname: Furukawa
authors.affiliation: Department of Obstetrics & Gynecology, Faculty of Medicine, University of Miyazaki, 5200 Kihara-Kiyotake, Miyazaki 892-1601, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sameshima
authors.affiliation: Department of Obstetrics & Gynecology, Faculty of Medicine, University of Miyazaki, 5200 Kihara-Kiyotake, Miyazaki 892-1601, Japan.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Obstetrics & Gynecology, Faculty of Medicine, University of Miyazaki, 5200 Kihara-Kiyotake, Miyazaki 892-1601, Japan.
authors.forename: Madhyastha
authors.initials: M
authors.lastname: Harishkumar
authors.affiliation: Department of Obstetrics & Gynecology, Faculty of Medicine, University of Miyazaki, 5200 Kihara-Kiyotake, Miyazaki 892-1601, Japan.
authors.forename: Tsuyomu
authors.initials: T
authors.lastname: Ikenoue
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002217:Carbachol / Q000494:pharmacology*; D002340:Carotid Artery Diseases / Q000150:complications; D002540:Cerebral Cortex / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018679:Cholinergic Agonists / Q000494:pharmacology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D007150:Immunohistochemistry; D017628:Microglia / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D066127:White Matter / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D018679:Cholinergic Agonists; D018696:Neuroprotective Agents; D011950:Receptors, Cholinergic; D014409:Tumor Necrosis Factor-alpha; D002217:Carbachol
keywords: Acetylcholine receptor agonist; Brain damage; Hypoxia-ischemia; Inflammation; Microglia; Newborn rat