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The PPARγ agonist rosiglitazone prevents cognitive impairment by inhibiting astrocyte activation and oxidative stress following pilocarpine-induced status epilepticus

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Abstract

Epilepsy is commonly associated with cognitive impairment. Astrocyte activation and oxidative stress occur following seizures, and play a role in the pathological injury of epilepsy with cognitive impairment. The peroxisome proliferator-activated receptor gamma (PPARγ) has been shown to exhibit neuroprotective and antioxidative effects in CNS diseases. Thus, we hypothesized that rosiglitazone, a PPARγ agonist, would prevent cognitive impairment by inhibiting astrocyte activation and regulating glutathione (GSH) homeostasis after status epilepticus (SE). Using a lithium pilocarpine-induced SE model, we found that rosiglitazone significantly prevented cognitive impairment induced by SE, and potently inhibited astrocyte activation with maintenance of GSH homeostasis in the hippocampus after SE. These protective effects were significantly reversed by co-treatment with the PPARγ antagonist T0070907. These data suggest that rosiglitazone can improve cognitive impairment, and inhibit astrocyte activation and oxidative damage following SE. Rosiglitazone may be a promising agent for treatment of epilepsy involving SE-induced cognitive impairment.

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Acknowledgments

This study was supported by the “Taiwan Guang Hua Fund”. We thank Dr. Dong Yan (Department of Immunology, Xijing Hospital) for his valuable technical advice.

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Authors and Affiliations

  1. Department of Neurology, The Second Affiliated Hospital, Medical School of Xi’an Jiaotong University, NO.157 West 5 Road, Xi’an, 710004, Shaanxi Province, China

    Sun Hong, Wu HaiQin, Zhang GuiLian, Zhang Ru, Zhan ShuQin, Wang HuQing, Yao Li & Du Yun

  2. Department of Neurology, People’s Liberation Army 401 Hospital, Qingdao, 266071, Shandong, China

    Yu Xin

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  1. Sun Hong
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  2. Yu Xin
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Correspondence to Sun Hong.

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Hong, S., Xin, Y., HaiQin, W. et al. The PPARγ agonist rosiglitazone prevents cognitive impairment by inhibiting astrocyte activation and oxidative stress following pilocarpine-induced status epilepticus. Neurol Sci 33, 559–566 (2012). https://doi.org/10.1007/s10072-011-0774-2

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  • DOI: https://doi.org/10.1007/s10072-011-0774-2

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