Quantitative Iron Neuroimaging Can Be Used to Assess the Effects of Minocycline in an Intracerebral Hemorrhage Minipig M
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ORIGINAL ARTICLE
Quantitative Iron Neuroimaging Can Be Used to Assess the Effects of Minocycline in an Intracerebral Hemorrhage Minipig Model Yang Yang 1 & Kaiyuan Zhang 1 & Xuntao Yin 2 & Xuejiao Lei 1 & Xuezhu Chen 1 & Ju Wang 1 & Yulian Quan 1 & Ling Yang 1 & Zhengcai Jia 1 & Qianwei Chen 1 & Jishu Xian 1 & Yongling Lu 3 & Qianying Huang 3 & Xuan Zhang 4 & Hua Feng 1 & Tunan Chen 1 Received: 26 July 2019 / Revised: 9 September 2019 / Accepted: 10 September 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019
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. Keywords Intracerebral hemorrhage . Minipig . Minocycline . Quantitative susceptibility mapping . Diffusion tensor imaging
Introduction Spontaneous intracerebral hemorrhage (ICH) is a lifethreatening condition with poor prognosis, accounting for ~ 10–15% of stroke-related hospitalizations [1]. As an important
degradation product of hemoglobin, brain iron overload serves essential roles in post-ICH brain injury [2]. Previous studies revealed that iron accumulation could last for several months following ICH [3], consequently resulting in hydrocephalus [4], neuronal death, white matter tract injury, and
Yang Yang and Kaiyuan Zhang contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12975-019-00739-2) contains supplementary material, which is available to authorized users. * Xuan Zhang [email protected]
2
Department of Radiology, Southwest Hospital, The Third Military Medical University (Army Military Medical University), Chongqing, China
3
Clinical Research Center, The Third Military Medical University (Arm
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