Efeito neuroprotetor da curcumina sobre o estresse oxidativo, inflamação, memória e dano neuronal de ratos submetidos à isquemia cerebral transitória

Abstract

The pathophysiology of cerebral ischemia involves a complex cascade of events which includes excitotoxicity, inflammation, oxidative stress and apoptosis. Curcumin is a polyphenol extracted from the rhizome of Curcuma longa. It has anti-inflammatory and antioxidant properties. In this study, we investigated the effects of curcumin on memory deficits, oxidative stress, inflammation and neuronal damage induced by transient cerebral ischemia (TCI). The TCI was induced by bilateral common carotid artery occlusion for 30 min followed by reperfusion. Vehicle or curcumin (6% DMSO in phosphate buffer) were orally administered 60 min before and daily after TCI. Cognitive evaluation was performed by using Y-maze, passive avoidance and water maze tests to assess working, spatial and aversive memories, respectively. To assess neuronal injury histological sections from hippocampus were stained with cresyl violet or FluoroJade C. The interleukin-1β and myeloperoxidase (MPO) contents from hippocampus were used for inflammatory evaluation. Oxidative stress was assessed by quantification of malondialdehyde (MDA), nitrite/nitrate, reduced glutathione (GSH) and superoxide dismutase (SOD) hippocampal. There were no changes in locomotor activity, neither in working memory. Curcumin prevented the TCI-induced early and late aversive memory deficits. The TCI impair spatial learning and memory. Curcumin treatment did not affect spatial learning, but showed a tendency to prevent the impairment on spatial memory. TCI promoted the increase in MPO activity and a tendency to increased concentrations of IL-1β and this effect was prevented by curcumin treatment. Curcumin treatment did not prevent the TCI-induced MDA increases 6h after surgery. Four days after surgery TCI showed a tendency to increase MDA contents and curcumin treatment lowered it. Curcumin prevented TCI- induced nitrite formation 6h after surgery and GSH depletion 24 hours after surgery. Curcumin protected the neurons from death 4d but not 7 days after TCI. Our results demonstrated that curcumin neuroprotection effects may be due to its anti-inflammatory and antioxidant properties.