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Biphasic activation of nuclear factor kappa B and expression of p65 and c-Rel after traumatic brain injury in rats

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Abstract

Background and object

Nuclear factor kappa B (NF-κB) functions as a key regulator in the central nervous system and regulates the inflammatory pathway. There are two peaks of cerebral NF-κB activation after neonatal hypoxia–ischemia and subarachnoid hemorrhage. Our previous studies found that NF-κB activity was up-regulated at an early stage and remained elevated at day 7 after traumatic brain injury (TBI). However, data are lacking regarding an overview of NF-κB activity and expression of NF-κB subunits after TBI. Hence, the current study was designed to detect the time course of NF-κB activation and expression of NF-κB p65 and c-Rel subunits around the contused cortex following TBI.

Methods

Adult Sprague–Dawley rats were randomly divided into sham and TBI groups at different time points. A TBI model was induced, and then the NF-κB DNA-binding activity in the surrounding areas of injured brain was detected by electrophoretic mobility shift assay. Western blotting was used to measure the protein levels of p65 and c-Rel in the nucleus. The concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay. Moreover, the distribution of c-Rel and p65 was examined by immunohistochemical studies.

Results

There were double peaks of cerebral cortical NF-κB activity, at 3 and 10 days post-injury. Additionally, protein levels of p65 were found to be elevated and peaked at 3 days after TBI, while levels of c-Rel were elevated significantly during the later phase of injury. Furthermore, TNF-α and IL-1β concentrations also showed a biphasic increase.

Conclusions

Biphasic activation of NF-κB could be induced after experimental TBI in rats. NF-κB p65 and c-Rel subunits were elevated at different post-TBI time periods, leading to a hypothesis that different NF-κB subunits might be involved in different pathophysiological processes after TBI.

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Abbreviations

TBI:

Traumatic brain injury

NF-κB:

Nuclear factor kappa B

IL-1β:

Interleukin-1β

TNF-α:

Tumor necrosis factor-α

IκB:

Inhibitor of NF-κB

ELISA:

Enzyme-linked immunosorbent assay

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Acknowledgments

We gratefully acknowledge the generous assistance from Dr. Gen-Bao Feng. This study was supported by the National Natural Science Foundation, China (NO. 81171170, 81371294), Nature Science Foundation of Jiangsu Province, China (BK2010459) and Military Medical Scientific and Technological Innovation Project (10Z024).

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Authors and Affiliations

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

    Yang-Chun Hu, Qing Sun, Wei Li, Ding-Ding Zhang, Biao Ma, Meng-Liang Zhou & Chun-Hua Hang

  2. Department of Neurosurgery, School of Medicine, Jinling Hospital, Southern Medical University (Guangzhou), Nanjing, Jiangsu Province, People’s Republic of China

    Song Li & Wei-De Li

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  1. Yang-Chun Hu
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  2. Qing Sun
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  6. Song Li
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  9. Chun-Hua Hang
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Correspondence to Chun-Hua Hang.

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Responsible Editor: John Di Battista.

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Hu, YC., Sun, Q., Li, W. et al. Biphasic activation of nuclear factor kappa B and expression of p65 and c-Rel after traumatic brain injury in rats. Inflamm. Res. 63, 109–115 (2014). https://doi.org/10.1007/s00011-013-0677-1

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  • DOI: https://doi.org/10.1007/s00011-013-0677-1

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