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Metformin Attenuates Neurological Deficit after Intracerebral Hemorrhage by Inhibiting Apoptosis, Oxidative Stress and Neuroinflammation in Rats

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Abstract

Intracerebral hemorrhage (ICH) can lead to brain damage and even death, and there is lack of effective therapeutic methods for treating ICH. Although recent studies have focused on the administration of metformin in treating stroke, there is no literature to support whether it can be used to treat ICH. Therefore, the aim of this study was to evaluate the possible effects of metformin on ICH and the underlying mechanisms of those effects. An ICH model was established in adult male Sprague–Dawley rats. Rats were randomly divided into three groups: sham group, ICH group, and ICH+metformin group. The neurobehavioral deficit scoring method was used to examine neurological function in rats. The levels of lipid peroxidation antioxidant enzyme and 8-iso-PGF2α were detected to evaluate oxidative stress. Survival of striatal neurons was examined by TUNEL staining, immunohistochemistry and HE staining. The levels of p-JNK, p-c-Jun and cleaved caspase-3 in the striatum were measured by western blotting. The results demonstrated that metformin protected rats from neurological deficits induced by ICH. Moreover, metformin reduced oxidative stress and preserved the survival of striatal neurons under ICH conditions. Furthermore, metformin downregulated the levels of apoptotic factors (p-JNK3, p-c-Jun and cleaved caspase-3) as well as pro-inflammatory cytokines (IL-1β, IL-4 and IL-6 and TNF-α). Collectively, we speculate that metformin may be a potential clinical treatment for ICH patients.

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Acknowledgements

This work was supported by the bureau of Xuzhou city science and technology (KC15SH037).

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Authors and Affiliations

  1. Medicine Intensive Care Unit, Xuzhou Children Hospital, Xuzhou, 221000, Jiangsu, People’s Republic of China

    Boxiang Qi, Libao Hu, Lei Zhu, Lei Shang, Xuecheng Wang, Na Liu, Nana Wen, Yao Hong & Daihua Fang

  2. Medicine Intensive Care Unit, Xuzhou Children Hospital, 18 Sudi North Road, Xuzhou, 221006, Jiangsu, People’s Republic of China

    Daihua Fang

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  1. Boxiang Qi
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  2. Libao Hu
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Correspondence to Daihua Fang.

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Qi, B., Hu, L., Zhu, L. et al. Metformin Attenuates Neurological Deficit after Intracerebral Hemorrhage by Inhibiting Apoptosis, Oxidative Stress and Neuroinflammation in Rats. Neurochem Res 42, 2912–2920 (2017). https://doi.org/10.1007/s11064-017-2322-9

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  • DOI: https://doi.org/10.1007/s11064-017-2322-9

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