title: Effects of agmatine on hypoxic microglia and activity of nitric oxide synthase.
abstract: Microglia are the resident macrophages of CNS and play a crucial role in maintaining homeostasis against various neuronal injuries. However, excessive activation of microglia may destroy healthy neurons as well as damaged neurons. We investigated neuroprotective effects of amgatine on hypoxic microglia using in vitro and in vivo models for transient hypoxia. For in vitro study, BV2 immortalized murine microglia were incubated with or without 100 μM of agmatine in a closed anaerobic chamber for 2h. After recovery in normoxic condition for 20 h, cell viability and the amount of nitrite generation were determined. For in vivo study, 100mg/kg of agmatine or equivalent volume of saline was intraperitoneally administered, and the left middle cerebral artery of adult male Sprague-Dawley rats was occluded for 90 min. After 24h from occlusion, the cortex and striatum of the forebrains was evaluated to check the immunoreactivity with a microglial marker, ionized calcium binding adaptor molecule 1 (Iba1), and inducible nitric oxide synthase (iNOS). Results showed that agmatine attenuated hypoxia-induced cytotoxicity and nitrite production by BV2 microglia. Agmatine also decreased the activities of microglia and NOS induced by transient middle cerebral artery occlusion. Finally, our findings reveal that agmatine may reduce microglial damages caused by transient hypoxia and suggest that agmatine may lead to a novel therapeutic strategy for hypoxic neuronal injuries.
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Ahn
authors.forename: Samin
authors.initials: S
authors.lastname: Hong
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Park
authors.forename: Won Taek
authors.initials: WT
authors.lastname: Lee
authors.forename: Kyung Ah
authors.initials: KA
authors.lastname: Park
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Lee
mesh_terms: D000376:Agmatine / Q000494:pharmacology* / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects*; D002461:Cell Line, Transformed; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D008840:Microfilament Proteins; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D016548:Prosencephalon / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D009573:Nitrites; D000376:Agmatine; D007770:L-Lactate Dehydrogenase; D052247:Nitric Oxide Synthase Type II