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Effects of Estrogen Receptor Antagonist ICI182.780 on a Rat Model of Traumatic Brain Injury

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Abstract

Understanding the roles of estrogen receptors (ERs) in the pathogenesis of traumatic brain injury (TBI) is an important topic of putative value for therapeutic approaches. The present study aimed to investigate the effects of a non-selective ER-α/β antagonist ICI182.780 (ICI) on a rat model of TBI. The TBI model was induced by the weight-drop injury and assessed by the Morris water maze (MWM). ICI was dissolved by DMSO and intracerebroventricularly administered before TBI. Adult male rats were randomly divided into three groups: sham + veh, TBI + veh, and TBI + ICI. The level of central estrogen in the cerebral spinal fluid (CSF) was assessed by ELISA. The expressions of aromatase cytochrome P-450 (AROM) and synaptophysin (SYN) as well as glial fibrillary acidic protein (GFAP) were evaluated by Western blotting and immunofluorescence analyses, respectively. Compared with the sham + veh group, the TBI + veh one showed longer escape latency and less number of platform crossings in the MWM test, an elevated level of endogenous estrogen in the CSF, and increased expressions of AROM and SYN as well as GFAP in the injured hippocampus. The TBI + ICI group displayed longer escape latency and less number of platform crossings in the MWM test and more expressions of GFAP in the hippocampus than that of the TBI + veh one. In conclusion, single-dose intracerebroventricular administration of ICI may increase the cognitive deficits and hippocampal astrocytic activation after TBI, but not for the central aromatization and hippocampal synaptogenesis.

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ACKNOWLEDGMENTS

This work was granted by the National Training Programs of Innovation and Entrepreneurship for Undergraduates of China (no. 201410392005). We thank teachers at the Experimental Animal Center of Fujian Medical University for their technique supports, and the wonderful youth time we struggled.

Funding

This work was funded by the National Training Programs of Innovation and Entrepreneurship for Undergraduates of China (no. 201410392005) to Dr. Jiangfeng Liao.

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Authors and Affiliations

  1. Fujian Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Medical University, No. 1 North University Road, 350122, Fuzhou, Fujian, China

    Jiangfeng Liao, Wenfen Fu, Hao Chen, Yanbing Chen & Wei Wang

Authors
  1. Jiangfeng Liao
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  2. Wenfen Fu
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  3. Hao Chen
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  4. Yanbing Chen
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  5. Wei Wang
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Corresponding authors

Correspondence to Jiangfeng Liao or Wei Wang.

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Conflict of interest. The authors declare no conflict of interests.

Ethical approval. All procedures involving animal subjects were reviewed and approved by the Institutional Animal Care and Use Committee at Fujian Medical University in compliance with the US National Institutes of Health Guidelines for the Care and Use of Laboratory Animals (NIH Publications nos. 80–23, revised in 1996).

Informed consent. This article does not contain any studies involving human participants performed by any of the authors.

Additional information

Jiangfeng Liao is a corresponding authors; address: Fujian Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Medical University, No. 1 North University Road, Fuzhou, Fujian, 350122, China; e-mail: jf.liao@qq.com, wangwei0976@163.com.

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Liao, J., Fu, W., Chen, H. et al. Effects of Estrogen Receptor Antagonist ICI182.780 on a Rat Model of Traumatic Brain Injury. Neurochem. J. 16, 190–199 (2022). https://doi.org/10.1134/S181971242202012X

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  • DOI: https://doi.org/10.1134/S181971242202012X

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