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Quantitative Iron Neuroimaging Can Be Used to Assess the Effects of Minocycline in an Intracerebral Hemorrhage Minipig Model

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Abstract

Iron-mediated toxicity is a key factor causing brain injury after intracerebral hemorrhage (ICH). This study was performed to investigate the noninvasive neuroimaging method for quantifying brain iron content using a minipig ICH model and assess the effects of minocycline treatment on ICH-induced iron overload and brain injury. The minipig ICH model was established by injecting 2 ml of autologous blood into the right basal ganglia, which were then subjected to the treatments of minocycline and vehicle. Furthermore, the quantitative susceptibility mapping (QSM) was used to quantify iron content, and diffusion tensor imaging (DTI) was performed to evaluate white matter tract. Additionally, we also performed immunohistochemistry, Western blot, iron assay, Perl’s staining, brain water content, and neurological score to evaluate the iron overload and brain injury. Interestingly, we found that the ICH-induced iron overload could be accurately quantified by the QSM. Moreover, the minocycline was quite beneficial for protecting brain injury by reducing the lesion volume and brain edema, preventing brain iron accumulation, downsizing ventricle enlargement, and alleviating white matter injury and neurological deficits. In summary, we suggest that the QSM be an accurate and noninvasive method for quantifying brain iron level, and the minocycline may be a promising therapeutic agent for patients with ICH.

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Funding

The present study was funded by Southwest Hospital (grant no. SWH2017JSZD-10 and SWH2016ZDCX1011) and the National Basic Research Program of China (973 Program, no. 2014CB541600).

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Author notes

  1. Yang Yang and Kaiyuan Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital, The Third Military Medical University (Army Military Medical University), Chongqing, China

    Yang Yang, Kaiyuan Zhang, Xuejiao Lei, Xuezhu Chen, Ju Wang, Yulian Quan, Ling Yang, Zhengcai Jia, Qianwei Chen, Jishu Xian, Hua Feng & Tunan Chen

  2. Department of Radiology, Southwest Hospital, The Third Military Medical University (Army Military Medical University), Chongqing, China

    Xuntao Yin

  3. Clinical Research Center, The Third Military Medical University (Army Military Medical University), Chongqing, China

    Yongling Lu & Qianying Huang

  4. Department of Neurosurgery, No. 989 Hospital of Joint Logistic Force (the 150th central hospital) of PLA, Luoyang, Henan Province, China

    Xuan Zhang

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  1. Yang Yang
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Contributions

Y.Y., K.Z., and T.C. designed the experiments. X.Y. scanned and analyzed all MRI images. X.L., X.C., J.W., Y.Q., L.Y., Z.J., Q.C., J.X., Y.L., and Q.H. preformed the experiments and discussed the results. X.Z. collected and analyzed all the present data. Y.Y., H.F., and T.C. wrote the draft and worked on the manuscript revision. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xuan Zhang, Hua Feng or Tunan Chen.

Ethics declarations

All experiments are reported in compliance with the Animal Research: Reporting in Vivo Experiments (ARRIVE) guidelines. The experimental protocols were approved by the Ethics Committee of the Third Military Medical University and performed according to the guide for the care and use of laboratory animals. All institutional and national guidelines for the care and use of laboratory animals were followed.

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The authors declare that they have no conflict of interest.

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Yang, Y., Zhang, K., Yin, X. et al. Quantitative Iron Neuroimaging Can Be Used to Assess the Effects of Minocycline in an Intracerebral Hemorrhage Minipig Model. Transl. Stroke Res. 11, 503–516 (2020). https://doi.org/10.1007/s12975-019-00739-2

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