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LPS Pretreatment Provides Neuroprotective Roles in Rats with Subarachnoid Hemorrhage by Downregulating MMP9 and Caspase3 Associated with TLR4 Signaling Activation

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An Erratum to this article was published on 06 December 2016

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Abstract

Subarachnoid hemorrhage (SAH), as a severe brain disease, has high morbidity and mortality. SAH usually induced neurological dysfunction or death and the treatment is far from satisfaction. Here, we investigated the effect of low dose of LPS pretreatment and underlying molecular mechanism in rat SAH model. Firstly, SAH model was induced by prechiasmal cistern injection method (SAH1) and common carotid artery-prechiasmal cistern shunt method (SAH2), respectively, to select the more suitable SAH model. At 6, 12, 24, 48, and 72 h after SAH, brain injury including neurological dysfunction, blood–brain barrier disruption, brain edema, and cell apoptosis were detected. And the expression of MMP9, HMGB1/TLR4, and caspase3 in cortex were also explored. Then, SB-3CT, an inhibitor of MMP9, was administrated to investigate the exact function of MMP9 in the brain injury at 24 h after SAH. Moreover, low dose of LPS was used to verify whether it had nerve protection after SAH and the mechanism involving in MMP9 and caspase 3 was investigated. Our results showed SAH1 seems to be the most suitable SAH model. In addition, MMP9 activated by HMGB1/TLR4 may promote or aggravate brain injury, while inhibiting MMP9 via SB-3CT exerted a neuroprotective effect. Moreover, LPS improved the neurological dysfunction, reduced Evans blue extravasation and brain edema, and inhibited cell apoptosis of cortex in rats with brain injury induced by SAH. Importantly, LPS pretreatment increased the expression level of TLR4, and decreased the level of MMP9 and caspase3. Therefore, the present study revealed that low dose of LPS pretreatment could provide neuroprotective effects on brain injury caused by SAH via downregulating MMP9 and caspase3 and activating TLR4 signal pathway.

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  • 06 December 2016

    An erratum to this article has been published.

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Acknowledgements

This research was supported by a grant of the National Science Foundation of China (No. 81271326, No.81100910), and supported by the Program for IRTSTYN, together with program Innovative Research Team In Science and Technology in Yunnan province (2016–2019).

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Authors and Affiliations

  1. Institute of Neurological Disease, and Department of Neurosurgery, Translational Neuroscience Center, the state key laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China

    Ting-Hua Wang, Liu-Lin Xiong, Shuai-Fen Yang, Chao You, Qing-Jie Xia, Yang Xu & Jia Liu

  2. Animal Zoology Department, Institute of Neuroscience, Kunming medical University, Kunming, 650000, China

    Piao Zhang & Jia Liu

  3. Yunnan Key Laboratory of Stem Cells and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, 650000, China

    Shu-Fen Wang

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  1. Ting-Hua Wang
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Ting-Hua Wang, Liu-Lin Xiong, Shuai-Fen Yang, Shu-Fen Wang and, Jia-Liu contributed equally to this work.

The original version of this article was revised: The author's name Shu-Feng Wang was changed to Shu-Fen Wang per request of authors.

An erratum to this article is available at https://doi.org/10.1007/s12035-016-0320-6.

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Wang, TH., Xiong, LL., Yang, SF. et al. LPS Pretreatment Provides Neuroprotective Roles in Rats with Subarachnoid Hemorrhage by Downregulating MMP9 and Caspase3 Associated with TLR4 Signaling Activation. Mol Neurobiol 54, 7746–7760 (2017). https://doi.org/10.1007/s12035-016-0259-7

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