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Telmisartan reduced cerebral edema by inhibiting NLRP3 inflammasome in mice with cold brain injury

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Summary

The aim of this study was to investigate the possible beneficial role of telmisartan in cerebral edema after traumatic brain injury (TBI) and the potential mechanisms related to the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) pyrin domain-containing 3 (NLRP3) inflammasome activation. TBI model was established by cold-induced brain injury. Male C57BL/6 mice were randomly assigned into 3, 6, 12, 24, 48 and 72 h survival groups to investigate cerebral edema development with time and received 0, 5, 10, 20 and 40 mg/kg telmisartan by oral gavage, 1 h prior to TBI to determine the efficient anti-edemic dose. The therapeutic window was identified by post-treating 30 min, 1 h, 2 h and 4 h after TBI. Blood-brain barrier (BBB) integrity, the neurological function and histological injury were assessed, at the same time, the mRNA and protein expression levels of NLRP3 inflammasome, IL-1β and IL-18 concentrations in peri-contused brain tissue were measured 24 h post TBI. The results showed that the traumatic cerebral edema occurred from 6 h, reached the peak at 24 h and recovered to the baseline 72 h after TBI. A single oral dose of 5, 10 and 20 mg/kg telmisartan could reduce cerebral edema. Post-treatment up to 2 h effectively limited the edema development. Furthermore, prophylactic administration of telmisartan markedly inhibited BBB impairment, NLRP3, apoptotic speck-containing protein (ASC) and Caspase-1 activation, as well as IL-1β and IL-18 maturation, subsequently improved the neurological outcomes. In conclusion, telmisartan can reduce traumatic cerebral edema by inhibiting the NLRP3 inflammasome-regulated IL-1β and IL-18 accumulation.

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Authors and Affiliations

  1. Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Xin Wei  (魏 欣), Chen-chen Hu  (胡晨晨), Ya-li Zhang  (张亚丽), Shang-long Yao  (姚尚龙) & Wei-ke Mao  (毛卫克)

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  1. Xin Wei  (魏 欣)
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  2. Chen-chen Hu  (胡晨晨)
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  3. Ya-li Zhang  (张亚丽)
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  4. Shang-long Yao  (姚尚龙)
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  5. Wei-ke Mao  (毛卫克)
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Corresponding author

Correspondence to Wei-ke Mao  (毛卫克).

Additional information

This project was supported by grants from the National Natural Science Foundation of China (No. 81270239) and the Natural Science Foundation of Hubei Province of China (No. 2014CFB200).

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Wei, X., Hu, Cc., Zhang, Yl. et al. Telmisartan reduced cerebral edema by inhibiting NLRP3 inflammasome in mice with cold brain injury. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 36, 576–583 (2016). https://doi.org/10.1007/s11596-016-1628-1

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  • DOI: https://doi.org/10.1007/s11596-016-1628-1

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