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Expression of the NLRP3 Inflammasome in Cerebral Cortex After Traumatic Brain Injury in a Rat Model

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Abstract

Inflammatory response plays an important role in the pathogenesis of secondary damage after traumatic brain injury (TBI). The inflammasome is a multiprotein complex involved in innate immunity and a number of studies have suggested that the inflammasome plays a critical role in a host inflammatory signaling. Nucleotide-binding domain, leucine-rich repeat, pyrin domain containing 3 (NLRP3) is a key component of the NLRP3-inflammasome, which also includes apoptotic speck-containing protein (ASC) with a cysteine protease (caspase) -activating recruitment domain and pro-caspase1. Activation of the NLRP3-inflammasome causes the processing and release of the interleukin 1 beta (IL-1β) and interleukin 18 (IL-18). Based on this, we hypothesized that the NLRP3-inflammasome could participate in the inflammatory response following TBI. However, the expression of NLRP3-inflammasome in cerebral cortex after TBI is not well known. Rats were randomly divided into control, sham and TBI groups (including 6 h, 1 day, 3 day and 7 day sub-group). TBI model was induced, and animals were sacrificed at each time point respectively. The expression of NLRP3-inflammasome was measured by quantitative real-time polymerase chain reaction, western blot and immunohistochemistry respectively. Immunofluorescent double labeling was performed to identify the cell types of NLRP3-inflammasome’s expression. Moreover, enzyme linked immunosorbent assay was used to detect the alterations of IL-1β and IL-18 at each time point post-injury. The results showed that, TBI could induce assembly of NLRP3-inflammasome complex, increased expression of ASC, activation of caspase1, and processing of IL-1β and IL-18. These results suggested that NLRP3-inflammasome might play an important role in the inflammation induced by TBI and could be a target for TBI therapy.

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Acknowledgments

This study was supported by Grants from National Natural Science Foundation, China (No. 81171170 for C. H. Hang, No. 8100053 for M. L. Zhou and No. 81271377 for Lin Zhu) and Nature Science Foundation of Jiangsu Province, China (BK2010459).

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Authors and Affiliations

  1. Department of Neurosurgery, School of Medicine, Jinling Hospital, Southern Medical University (Guangzhou), 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, People’s Republic of China

    Huan-Dong Liu, Zhen-Rui Chen, Wei Shen & Chun-Hua Hang

  2. Department of Neurosurgery, School of Medicine, Jinling Hospital, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, People’s Republic of China

    Wei Li, Yang-Chun Hu, Ding-Ding Zhang, Meng-Liang Zhou, Lin Zhu & Chun-Hua Hang

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  1. Huan-Dong Liu
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  2. Wei Li
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Correspondence to Chun-Hua Hang.

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Liu, HD., Li, W., Chen, ZR. et al. Expression of the NLRP3 Inflammasome in Cerebral Cortex After Traumatic Brain Injury in a Rat Model. Neurochem Res 38, 2072–2083 (2013). https://doi.org/10.1007/s11064-013-1115-z

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  • DOI: https://doi.org/10.1007/s11064-013-1115-z

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