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脑出血猪模型中血肿周围组织的系列代谢评估

Serial Metabolic Evaluation of Perihematomal Tissues in the Intracerebral Hemorrhage Pig Model.

作者信息

Haque Muhammad E, Gabr Refaat E, George Sarah D, Zhao Xiurong, Boren Seth B, Zhang Xu, Ting Shun-Ming, Sun Gunghua, Hasan Khader M, Savitz Sean, Aronowski Jaroslaw

机构信息

Institute for Stroke and Cerebrovascular Diseases, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States.

Diagnostic and Interventional Imaging, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States.

出版信息

Front Neurosci. 2019 Aug 21;13:888. doi: 10.3389/fnins.2019.00888. eCollection 2019.

Abstract

PURPOSE

Perihematomal edema (PHE) occurs in patients with intracerebral hemorrhage (ICH) and is often used as surrogate of secondary brain injury. PHE resolves over time, but little is known about the functional integrity of the tissues that recover from edema. In a pig ICH model, we aimed to assess metabolic integrity of perihematoma tissues by using non-invasive magnetic resonance spectroscopy (MRS).

MATERIALS AND METHODS

Fourteen male Yorkshire pigs with an average age of 8 weeks were intracerebrally injected with autologous blood to produce ICH. Proton MRS data were obtained at 1, 7, and 14 days after ICH using a whole-body 3.0T MRI system. Point-resolved spectroscopy (PRESS)-localized 2D chemical shift imaging (CSI) was acquired. The concentration of -Acetylaspartate (NAA), Choline (Cho), and Creatine (Cr) were measured within the area of PHE, tissues adjacent to the injury with no or negligible edema (ATNE), and contralesional brain tissue. A linear mixed model was used to analyze the evolution of metabolites in perihematomal tissues, with -value < 0.05 indicating statistical significance.

RESULTS

The perihematoma volume gradually decreased from 2.38 ± 1.23 ml to 0.41 ± 0.780 ml ( < 0.001) over 2 weeks. Significant ( 0.001) reductions in NAA, Cr, and Cho concentrations were found in the PHE and ATNE regions compared to the contralesional hemisphere at day 1 and 7 after ICH. All three metabolites were significantly ( < 0.001) restored in the PHE tissue on day 14, but remained persistently low in the ATNE area, and unaltered in the contralesional voxel.

CONCLUSION

This study highlights the potential of MRS to probe salvageable tissues within the perihematoma in the sub-acute phase of ICH. Altered metabolites within the PHE and ATNE regions in addition to edema and hematoma volumes were explored as possible markers for tissue recovery. Perihematomal tissue with PHE demonstrated a more reversible injury compared to the tissue adjacent to the injury without edema, suggesting a potentially beneficial role of edema.

摘要

目的

脑出血(ICH)患者会出现血肿周围水肿(PHE),其常被用作继发性脑损伤的替代指标。PHE会随着时间消退,但对于从水肿中恢复的组织的功能完整性知之甚少。在猪ICH模型中,我们旨在通过使用非侵入性磁共振波谱(MRS)评估血肿周围组织的代谢完整性。

材料与方法

14只平均年龄为8周的雄性约克夏猪经脑内注射自体血以产生ICH。在ICH后1天、7天和14天,使用全身3.0T MRI系统获取质子MRS数据。采集点分辨波谱(PRESS)定位的二维化学位移成像(CSI)。在PHE区域、无或仅有可忽略水肿的损伤邻近组织(ATNE)以及对侧脑组织内测量N-乙酰天门冬氨酸(NAA)、胆碱(Cho)和肌酸(Cr)的浓度。使用线性混合模型分析血肿周围组织中代谢物的演变,P值<0.05表示具有统计学意义。

结果

在2周内,血肿周围体积从2.38±1.23 ml逐渐减小至0.41±0.780 ml(P<0.001)。与对侧半球相比,在ICH后第1天和第7天,PHE和ATNE区域的NAA、Cr和Cho浓度显著降低(P<0.001)。在第14天,PHE组织中所有三种代谢物均显著恢复(P<0.001),但在ATNE区域仍持续较低,而在对侧体素中未改变。

结论

本研究突出了MRS在ICH亚急性期探测血肿周围可挽救组织的潜力。除了水肿和血肿体积外,还探索了PHE和ATNE区域内代谢物的改变作为组织恢复的可能标志物。与无水肿的损伤邻近组织相比,伴有PHE的血肿周围组织表现出更可逆的损伤,提示水肿可能具有有益作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/042b/6712426/994f8f2bfc15/fnins-13-00888-g001.jpg

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