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SRC-3 Deficiency Exacerbates Neurological Deficits in a Mouse Model of Intracerebral Hemorrhage: Role of Oxidative Stress

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Abstract

Intracerebral hemorrhage (ICH) causes long term neurological abnormality or death. Oxidative stress is closely involved in ICH mediated brain damage. Steroid receptor cofactor 3 (SRC-3), a p160 family member, is widely expressed in the brain and regulates transactivation of Nrf2, a key component of antioxidant response. Our study aims to test if SRC-3 is implicated in ICH mediated brain injury. We first examined levels of SRC-3 and oxidative stress in the brain of mice following ICH and analyzed their correlation. Then ICH was induced in wild type (WT) and SRC-3 knock out mice and how SRC-3 deletion affected ICH induced brain damage, oxidative stress and behavioral outcome was assessed. We found that SRC-3 mRNA and protein expression levels were reduced gradually after ICH induction in WT mice along with an increase in oxidative stress levels. Correlation analysis revealed that SRC-3 mRNA levels negatively correlated with oxidative stress. Deletion of SRC-3 further increased ICH induced brain edema, neurological deficit score and oxidative stress and exacerbated ICH induced behavioral abnormality including motor dysfunction and cognitive impairment. Our findings suggest that SRC-3 is involved in ICH induced brain injury, probably through modulation of oxidative stress.

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Data could be achieved upon reasonable request to the corresponding author.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (No. 81801188) and the Natural Science Foundation of Hunan Province (No. 2019JJ40421).

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Authors and Affiliations

  1. Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China

    Mingyang Deng & Huan Yuan

  2. Department of Neurology, The Second Xiangya Hospital, Central South University, No. 139 Renmin Road, Changsha, 410011, Hunan, China

    Jianyang Liu, Jialin He, Ziwei Lan, Zhiping Hu & Han Xiao

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  1. Mingyang Deng
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Correspondence to Han Xiao.

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Deng, M., Liu, J., He, J. et al. SRC-3 Deficiency Exacerbates Neurological Deficits in a Mouse Model of Intracerebral Hemorrhage: Role of Oxidative Stress. Neurochem Res 46, 2969–2978 (2021). https://doi.org/10.1007/s11064-021-03399-7

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