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.
Subject(s)
Brain Ischemia/drug therapy , Cinnamates/pharmacology , Depsides/pharmacology , Memory Disorders/prevention & control , Neuroprotective Agents/pharmacology , Animals , Astrocytes/drug effects , Astrocytes/pathology , Astrocytes/physiology , Brain/drug effects , Brain/metabolism , Brain/pathology , Brain Ischemia/complications , Brain Ischemia/pathology , Brain Ischemia/physiopathology , Brain-Derived Neurotrophic Factor/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Gliosis/drug therapy , Gliosis/etiology , Gliosis/pathology , Gliosis/physiopathology , Infarction, Middle Cerebral Artery , Male , Memory Disorders/etiology , Memory Disorders/pathology , Memory Disorders/physiopathology , Memory, Short-Term/drug effects , Memory, Short-Term/physiology , Mice , Motor Activity/drug effects , Motor Activity/physiology , Peroxidase/metabolism , Recognition, Psychology/drug effects , Recognition, Psychology/physiology , Spatial Memory/drug effects , Spatial Memory/physiology , Synapses/drug effects , Synapses/pathology , Synapses/physiology , Rosmarinic AcidABSTRACT
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.
