title: Caffeic acid protects mice from memory deficits induced by focal cerebral ischemia.
abstract: Brain ischemia pathophysiology involves a complex cascade of events such as inflammation and oxidative stress that lead to neuronal loss and cognitive deficits. Caffeic acid (CA) is a natural phenolic compound with antioxidant and anti-inflammatory properties. To evaluate the neuroprotective efficacy of this compound in mice subjected to a permanent middle cerebral artery occlusion, animals were pretreated and post-treated with CA, 2, 20, and 60 mg/kg/day, intraperitoneally, at 24, 48, 72, 96, or 120 h after ischemia. Animals were evaluated at 24 h after the permanent middle cerebral artery occlusion for brain infarction and neurological deficit score. At 72 h after the occlusion, animals were evaluated for locomotor activity, working memory, and short-term aversive memory; long-term aversive memory was evaluated 24 h after the evaluation of short-term aversive memory. Finally, at 120 h after the event, spatial memory and the expression levels of synaptophysin (SYP), SNAP-25, and caspase 3 were evaluated. The treatment with CA reduced the infarcted area and improved neurological deficit scores. There was no difference in locomotor activity between groups. The working, spatial, and long-term aversive memory deficits improved with CA. Furthermore, western blotting data showed that the expression of SYP, which correlates with synaptic formation and function, decreased after ischemic insult, and CA inhibited the reduction of SYP expression. Ischemia also increased, and CA treatment decreased, caspase 3 expression. These results suggest that CA exerts neuroprotective and antidementia effects, at least in part, by preventing the loss of neural cells and synapses in ischemic brain injury.
authors.affiliation: aPost-Graduate Programme in Medical Sciences, Department of Clinical Medicine bPost-Graduate Programme in Pharmacology, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará cInstitute of Biomedicine of Brazilian Semi-arid, Fortaleza, Brazil.
authors.forename: Francisco Diego
authors.initials: FD
authors.lastname: Pinheiro Fernandes
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Fontenele Menezes
authors.forename: Julliana Catharina
authors.initials: JC
authors.lastname: de Sousa Neves
authors.forename: Analu Aragão
authors.initials: AA
authors.lastname: Fonteles
authors.forename: Ana Thais Araújo
authors.initials: AT
authors.lastname: da Silva
authors.forename: Patrícia
authors.initials: P
authors.lastname: de Araújo Rodrigues
authors.forename: Marta Regina
authors.initials: MR
authors.lastname: Santos do Carmo
authors.forename: Carolina Melo
authors.initials: CM
authors.lastname: de Souza
authors.forename: Geanne Matos
authors.initials: GM
authors.lastname: de Andrade
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002109:Caffeic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016708:Synaptophysin / Q000235:genetics; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics; D013997:Time Factors
chemical_list: D002109:Caffeic Acids; D018696:Neuroprotective Agents; C494209:Snap25 protein, mouse; D016708:Synaptophysin; D050825:Synaptosomal-Associated Protein 25; D053148:Caspase 3; C040048:caffeic acid