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Gabapentin Alleviates Brain Injury in Intracerebral Hemorrhage Through Suppressing Neuroinflammation and Apoptosis

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Abstract

Neuroinflammation plays an important role in brain tissue injury during intracerebral hemorrhage. Gabapentin can reduce inflammation and oxidative stress through inhibiting nuclear factor κB (NFκB) signals. Here, we showed that gabapentin reduced brain tissue injury in ICH through suppressing NFκB-mediated neuroinflammation. ICH was induced by injecting collagenase IV into the right striatum of Sprague–Dawley rats. PC12 and BV2 cells injury induced by Hemin were used to simulate ICH in vitro. Inflammation and apoptosis were assessed in rat brain tissue and in vitro cells. The neurobehavioral scores were significantly decreased in ICH rats compared with sham rats. Phosphorylated IκB-α and cleaved caspase3, and apoptosis rate were significantly higher in tissue surrounding the hematoma than in brain tissues from rats subjected to sham surgery. Furthermore, serum IL-6 levels in ICH rats were higher than in sham rats. Gabapentin treatment significantly improved the behavioral scores, decreased levels of phosphorylated IκB-α and cleaved caspase3, apoptosis rate, and serum IL-6 level in ICH rats. Hemin-treated BV2 cells displayed higher levels of phosphorylated IκB-α, cleaved caspase3, and IL-6 in the supernatant compared with vehicle-treated cells. Hemin treatment induced a significantly lower level of peroxisome proliferator-activated receptor γ (PPARγ) in BV2 cells. BV2-PC12 co-culture cells treated by hemin displayed higher levels of cleaved caspase3 in PC12 cells. Furthermore, gabapentin treatment could reduce these effects induced by hemin and the protective effects of gabapentin were significantly attenuated by PPARγ inhibitor. Therefore, gabapentin may reduce inflammation and apoptosis induced by the ICH through PPARγ-NFκB pathway.

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Data availability

The datasets d analyzed during the current study available from the corresponding author on reasonable request.

Abbreviations

ICH:

Intracerebral hemorrhage

SBI:

Secondary brain injury

NFκB:

Nuclear factor κB

IKK:

IκB kinase

PPARγ:

Peroxisome proliferator-activated receptor γ

IL-6:

Interleukin-6

TNF-α:

Tumor necrosis factor α

IFN-γ:

Interferon gamma

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Acknowledgements

This research was supported by the National Key R & D Program Intergovernmental Cooperation on International Scientific and Technological Innovation of the Ministry of Science and Technology of China (2017YFE0110400), the National Natural Science Foundation of China (81870984), Special Project for the Construction of Hebei Province International Science and Technology Cooperation Base (193977143D), and Government funded Project on Training of Outstanding Clinical Medical Personnel and Basic Research Projects of Hebei Province in the Year of 2019.

Funding

Funding was provided by National Key R & D Program Intergovernmental Cooperation on International Scientific and Technological Innovation of the Ministry of Science and Technology of China (Grant No.: 2017YFE0110400), National Natural Science Foundation of China (Grant No.: 81870984), Special Project for the Construction of Hebei Province International Science and Technology Cooperation Base (Grant No.: 193977143D), Government funded Project on Training of Outstanding Clinical Medical Personnel and Basic Research Projects of Hebei Province in the Year of 2019

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Author notes

  1. Xiaopeng Li, Bingqian Wang, and Ning Yu contribute equally to this study.

Authors and Affiliations

  1. Department of Neurosurgery, The Second Hospital of Hebei Medical University, 215 Heping Road, Shijiazhuang, 050000, HeBei, China

    Xiaopeng Li, Bingqian Wang, Liang Yang, Chengrui Nan, Zhimin Sun, Lisi Guo & Zongmao Zhao

  2. Department of Neurosurgery, The First Hospital of Handan City, Handan, 056000, HeBei, China

    Xiaopeng Li

  3. Department of Neurosurgery, Affiliated Xing Tai People Hospital of Hebei Medical University, Xingtai, 054000, HeBei, China

    Bingqian Wang

  4. Department of Anesthesiology and Intensive Care Unit, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, HeBei, China

    Ning Yu

  5. Department of Neurosurgery, The Third Hospital of Shijiazhuang City, Shijiazhuang, 050000, HeBei, China

    Zhimin Sun

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  1. Xiaopeng Li
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Contributions

XL, DL, and ZZ designed the study and write the manuscript. XL, BW, NY, LY, CN, ZS performed behavioral testing and immunohistostaining experiments and analyzed the data. XL, BW, LG, and ZZ, contributes to revising the manuscript. All authors read and approved the final manuscript.

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Correspondence to Zongmao Zhao.

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The authors declare that they have no competing interests.

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All animal usage and experimental protocols and surgical procedures were approved by the Ethics Committee of The Second Hospital of Hebei Medical University.

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Li, X., Wang, B., Yu, N. et al. Gabapentin Alleviates Brain Injury in Intracerebral Hemorrhage Through Suppressing Neuroinflammation and Apoptosis. Neurochem Res 47, 3063–3075 (2022). https://doi.org/10.1007/s11064-022-03657-2

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