title: Activation of acetylcholine receptors and microglia in hypoxic-ischemic brain damage in newborn rats.
abstract: OBJECTIVE
  We previously showed that acetylcholine receptor (AChR) agonist reduced hypoxic-ischemic brain damage in the newborn rats. To further investigated the interaction between hypoxia and chorinergic anti-inflammatory pathway, we examined the effect of AChR antagonist on brain damage and to see the relation between microglial activation and protective effect of AChR agonist.
  
  
  METHODS
  Seven-day-old Wistar rats were divided into 2 groups, one receiving AChR antagonists to see if they have deleterious effects on hypoxic-ischemic brain damage, and the other receiving AChR agonist, carbachol, to investigate the emergence of microglia in the hippocampus. Rats were subjected to left carotid artery ligation followed by 8% hypoxia. Brains were analyzed histologically and immunohistochemically.
  
  
  RESULTS
  Antagonists of AChRs significantly enhanced brain damage in 1-h hypoxia-ischemia. In particular, the nicotinic AChR antagonist showed a marked enhancement of brain damage compared to the saline controls (p<0.01). The hippocampal CA1 was most vulnerable to any AChR antagonists, while the cortex was least vulnerable and only responsive to a higher dose of non-selective nAChR antagonist. Carbachol showed significantly less accumulation of microglia in the hippocampus than the saline controls (p<0.01) in hypoxia-ischemia.
  
  
  CONCLUSIONS
  An AchR-responsive pathway in the brain plays an important role in modifying perinatal brain damage, in which microglial accumulation may be involved.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. snhm10@fc.miyazaki-u.ac.jp
authors.forename: Seishi
authors.initials: S
authors.lastname: Furukawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sameshima
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Tsuyomu
authors.initials: T
authors.lastname: Ikenoue
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018679:Cholinergic Agonists / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004195:Disease Models, Animal; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D017628:Microglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000378:metabolism*
chemical_list: D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D011950:Receptors, Cholinergic