title: Rosmarinic acid prevents against memory deficits in ischemic mice.
abstract: Polyphenols have neuroprotective effects after brain ischemia. It has been demonstrated that rosmarinic acid (RA), a natural phenolic compound, possesses antioxidant and anti-inflammatory properties. To evaluate the effectiveness of RA against memory deficits induced by permanent middle cerebral artery occlusion (pMCAO) mice were treated with RA (0.1, 1, and 20mg/kg/day, i.p. before ischemia and during 5 days). Animals were evaluated for locomotor activity and working memory 72 h after pMCAO, and spatial and recognition memories 96 h after pMCAO. In addition, in another set of experiments brain infarction, neurological deficit score and myeloperoxidase (MPO) activity were evaluates 24h after the pMCAO. Finally, immunohistochemistry, and western blot, and ELISA assay were used to analyze glial fibrillary acidic protein (GFAP), and synaptophysin (SYP) expression, and BDNF level, respectively. The working, spatial, and recognition memory deficits were significantly improved with RA treatment (20mg/kg). RA reduced infarct size and neurological deficits caused by acute ischemia. The mechanism for RA neuroprotection involved, neuronal loss suppression, and increase of synaptophysin expression, and increase of BDNF. Furthermore, the increase of MPO activity and GFAP immunireactivity were prevented in MCAO group treated with RA. These results suggest that RA exerts memory protective effects probably due to synaptogenic activity and anti-inflammatory action.
authors.affiliation: Post-Graduate Programme in Pharmacology, Department of Physiology and Pharmacology, Fortaleza, Brazil; Institute of Biomedicine of Brazilian Semi-Arid, Fortaleza, Brazil.
authors.forename: Analu Aragão
authors.initials: AA
authors.lastname: Fonteles
authors.affiliation: Post-Graduate Programme in Medical Sciences, Department of Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Carolina Melo
authors.initials: CM
authors.lastname: de Souza
authors.affiliation: Post-Graduate Programme in Pharmacology, Department of Physiology and Pharmacology, Fortaleza, Brazil.
authors.forename: Julliana Catharina
authors.initials: JC
authors.lastname: de Sousa Neves
authors.affiliation: Post-Graduate Programme in Medical Sciences, Department of Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Ana Paula Fontenele
authors.initials: AP
authors.lastname: Menezes
authors.affiliation: Post-Graduate Programme in Pharmacology, Department of Physiology and Pharmacology, Fortaleza, Brazil.
authors.forename: Marta Regina
authors.initials: MR
authors.lastname: Santos do Carmo
authors.affiliation: Post-Graduate Programme in Medical Sciences, Department of Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Francisco Diego Pinheiro
authors.initials: FD
authors.lastname: Fernandes
authors.affiliation: Post-Graduate Programme in Medical Sciences, Department of Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Patrícia Rodrigues
authors.initials: PR
authors.lastname: de Araújo
authors.affiliation: Post-Graduate Programme in Pharmacology, Department of Physiology and Pharmacology, Fortaleza, Brazil; Post-Graduate Programme in Medical Sciences, Department of Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil; Institute of Biomedicine of Brazilian Semi-Arid, Fortaleza, Brazil. Electronic address: gmatos@ufc.br.
authors.forename: Geanne Matos
authors.initials: GM
authors.lastname: de Andrade
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002934:Cinnamates / Q000494:pharmacology*; D053630:Depsides / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005911:Gliosis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D000097123:Rosmarinic Acid
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002934:Cinnamates; D053630:Depsides; D018696:Neuroprotective Agents; D009195:Peroxidase; D000097123:Rosmarinic Acid
keywords: Cerebral ischemia; Memory deficits; Polyphenols; Rosmarinic acid