title: Melatonin reduces infarction volume in a photothrombotic stroke model in the wild-type but not cyclooxygenase-1-gene knockout mice.
abstract: Cyclooxygenase (COX)-2 plays a harmful role in cerebral ischemic/reperfusion injury, but the role of COX-1 is uncertain. In the present study, cerebral infarct was induced by photothrombosis. Intraperitoneal injections of melatonin at 15 g/kg or its vehicle were made at 0.5 hr before stroke and 24 and 48 hr after stroke. Cerebral blood flow (CBF) in the penumbra was monitored during stroke using a laser Doppler flowmeter. Sensorimotor behavior was evaluated using the turning in an alley and falling from a pole tests at 1 hr before stroke and 24 and 48 hr after stroke. Infarct volume was determined from the T2-weighted magnetic resonance images at 72 hr after stroke. During the first 15 min of stroke, CBF decreased in the penumbra in both homozygous COX-1-gene knockout and wild-type mice. Melatonin treatment improved the penumbral CBF in the wild-type mice. Mild poststroke impairment in sensorimotor behavior was detected by the turning in an alley test in which the COX-1-gene knockout mice performed better. Melatonin treatment did not affect the poststroke sensorimotor behavior. The relative infarct volume at 72 hr after stroke was 8.1% and 8.4% in the COX-1-gene knockout and wild-type mice, respectively. Melatonin treatment reduced the relative infarct volume to 6.3% in the latter but not in the former (8.2%). Thus, COX-1-gene knockout does not affect the brain's susceptibility to photothrombotic stroke. Melatonin treatment reduces infarct size in the wild-type mice following photothrombotic stroke partly via maintenance of penumbral CBF in which the COX-1-gene may play a role.
authors.affiliation: Division of Neurology, University Department of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Liang Yu
authors.initials: LY
authors.lastname: Zou
authors.forename: Raymond Tak Fai
authors.initials: RT
authors.lastname: Cheung
authors.forename: Sirun
authors.initials: S
authors.lastname: Liu
authors.forename: Geng
authors.initials: G
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Huang
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D001929:Brain Edema / Q000473:pathology; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000235:genetics*; D004195:Disease Models, Animal; D017078:Laser-Doppler Flowmetry; D008550:Melatonin / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D018345:Mice, Knockout; D009048:Motor Skills; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000503:physiopathology; D012395:Rose Bengal; D013927:Thrombosis / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D012395:Rose Bengal; D051545:Cyclooxygenase 1; D008550:Melatonin