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Quercetin Attenuates Cell Apoptosis in Focal Cerebral Ischemia Rat Brain Via Activation of BDNF–TrkB–PI3K/Akt Signaling Pathway

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Abstract

Many studies have demonstrated that apoptosis play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Neuroprotective effect of quercetin has been shown in a variety of brain injury models including ischemia/reperfusion. It is not clear whether BDNF–TrkB–PI3K/Akt signaling pathway mediates the neuroprotection of quercetin, though there has been some reports on the quercetin increased brain-derived neurotrophic factor (BDNF) level in brain injury models. We therefore first examined the neurological function, infarct volume and cell apoptosis in quercetin treated middle cerebral artery occlusion (MCAO) rats. Then the protein expression of BDNF, cleaved caspase-3 and p-Akt were evaluated in either the absence or presence of PI3K inhibitor (LY294002) or tropomyosin receptor kinase B (TrkB) receptor antagonist (K252a) by immunohistochemistry staining and western blotting. Quercetin significantly improved neurological function, while it decreased the infarct volume and the number of TdT mediated dUTP nick end labeling positive cells in MCAO rats. The protein expression of BDNF, TrkB and p-Akt also increased in the quercetin treated rats. However, treatment with LY294002 or K252a reversed the quercetin-induced increase of BDNF and p-Akt proteins and decrease of cleaved caspase-3 protein in focal cerebral ischemia rats. These results demonstrate that quercetin can decrease cell apoptosis in the focal cerebral ischemia rat brain and the mechanism may be related to the activation of BDNF–TrkB–PI3K/Akt signaling pathway.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 30801526 to Ruiqin Yao), the Natural Science Foundation for Universities in Jiangsu Province (No.09KJD310010 to Ruiqin Yao) and the Foundation of Xuzhou Medical College (No.09KJZ14 to Ruiqin Yao).

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  1. Department of Neurobiology, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu, People’s Republic of China

    Rui-Qin Yao, Da-Shi Qi, Hong-Li Yu, Jing Liu, Li-Hua Yang & Xiu-Xiang Wu

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  1. Rui-Qin Yao
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  2. Da-Shi Qi
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  3. Hong-Li Yu
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  4. Jing Liu
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  6. Xiu-Xiang Wu
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Correspondence to Rui-Qin Yao.

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Yao, RQ., Qi, DS., Yu, HL. et al. Quercetin Attenuates Cell Apoptosis in Focal Cerebral Ischemia Rat Brain Via Activation of BDNF–TrkB–PI3K/Akt Signaling Pathway. Neurochem Res 37, 2777–2786 (2012). https://doi.org/10.1007/s11064-012-0871-5

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  • DOI: https://doi.org/10.1007/s11064-012-0871-5

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