Resveratrol attenuates brain damage in permanent focal cerebral ischemia via activation of PI3K/Akt signaling pathway in rats.

Objective: The aim of this study was to evaluate the potential molecular mechanism of resveratrol (RSV) that attenuates brain damage from focal cerebral ischemia.

Methods: To investigate whether phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway was involved in RSV anti-inflammatory and neuroprotective properties. Middle cerebral artery occlusion (MCAO) animal model was used in this study. Adult male Sprague-Dawley (SD) rats underwent MCAO, and then received treatment with RSV or vehicle after the onset of ischemia. PI3K inhibitor LY294002 was injected intracerebroventricularly to inhibit the PI3K/Akt signaling pathway. Neurological deficit scores and cerebral water content were assessed 24 h after MCAO. The inflammatory factors interleukin (IL)-1β, tumor necrosis factor (TNFα), and cyclooxygenase-2 (COX2) mRNA level were examined by real-time PCR. The enzymatic activity of myeloperoxidase (MPO) was measured 24 h after MCAO. The protein expression of phospho-Akt and COX2 in ischemic brain were determined by western blot.

Results: RSV significantly reduced neurological deficit scores, cerebral water content and the enzymatic activity of MPO, all of which were abolished by LY294002 administration. Real-time PCR showed that RSV significantly suppressed the upregulation of the inflammatory factors IL-1β, TNFα, COX2 mRNA levels. RSV significantly inhibited upregulated the protein expression of COX2 24 h after MCAO, which effect was abolished by LY294002 administration.

Conclusions: RSV attenuated ischemic brain damage induced by cerebral artery occlusion mainly through PI3K/Akt signaling pathway. Abbreviation: MCAO: Middle cerebral artery occlusion; RSV: resveratrol; PI3K/Akt: phosphatidylinositol 3-kinase/Akt; TNF: tumor necrosis factor; COX2: cyclooxygenase-2; MPO: myeloperoxidase; IL: interleukin.