Efeito neuroprotetor do ácido cafeico em camundongos submetidos á isquemia cerebral focal permanente

Abstract

Brain ischemia results from the acute interruption of blood flow to the brain tissue vascular accident resulting in the decrease of glucose and oxygen to the tissues and consequently to a rapid loss of neurological function. It is the second leading cause of death worldwide and a major cause of disability according to the World Health Organization. Brain stroke pathophysiology involves a complex cascade of events such as inflammation and oxidative stress that lead to neuronal loss and cognitive deficits. Caffeic acid 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 (pMCAO), animals were pre-and post-treated with caffeic acid 2, 20 and 60mg/kg, i.p. during 24, 48, 72, 96 or 120h after ischemia. Animals were evaluated at 24 h after the pMCAO for brain infarction and neurological deficit score. At 72 h after the occlusion, animals were evaluated for locomotor activity, working memory and short aversive memory; late aversive memory was evaluated 24 h after the evaluation of short aversive memory. Finally, at 120 h after the event, spatial memory and the expression levels of synaptophysin, SNAP 25 and caspase 3 were evaluated. The treatment with caffeic acid reduced the infarcted area and improved neurological deficit scores. There was no difference in locomotor activity between groups. The working, spatial and late aversive memory deficits were improved by caffeic acid. Furthermore, western blotting data showed that the expression of synaptophysin which correlates with synaptic formation and function, decreased after ischemic insult, caffeic acid inhibited the reduction of synaptophysin expression. The treatment also decreased caspase 3 expression. These results suggest that caffeic acid possesses neuroprotective and anti-dementia properties, at least in part, by preventing the loss of neural cells and synapses in ischemic brain injury.