Wang Wenzhu, Zhang Hong, Lee Doon-Hoon, Yu Jintao, Cheng Tian, Hong Michael, Jiang Shanshan, Fan Heng, Huang Xi, Zhou Jinyuan, Wang Jian
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China.
Division of MR Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Radiology, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
Brain Behav Immun. 2017 Aug;64:344-353. doi: 10.1016/j.bbi.2017.04.019. Epub 2017 Apr 26.
This study was designed to investigate whether functional and molecular MRI techniques are sensitive biomarkers for assessment of neuroinflammation and drug efficacy after traumatic brain injury (TBI) in rats. We subjected rats to a controlled cortical impact model and used behavioral tests, histology, and immunofluorescence to assess whether flavonoid pinocembrin provides cerebral protection and improves functional recovery. Most importantly, we used multiple noninvasive structural, functional, and molecular MRI techniques to examine whether the pinocembrin-related neuroprotection and attenuation of neuroinflammation can be detected in vivo. Significant increases in cerebral blood flow (CBF) and amide proton transfer-weighted (APTw) MRI signals were observed in the perilesional areas in untreated TBI rats at 3days and could be attributed to increased glial response. In addition, increased apparent diffusion coefficient and decreased magnetization transfer ratio signals in untreated TBI rats over time were likely due to edema. Post-treatment with pinocembrin decreased microglial/macrophage activation at 3days, consistent with the recovery of CBF and APTw MRI signals in regions of secondary injury. These findings suggest that pinocembrin provides cerebral protection for TBI and that multiple MRI signals, CBF and APTw in particular, are sensitive biomarkers for identification and assessment of neuroinflammation and drug efficacy in the TBI model.
本研究旨在调查功能和分子磁共振成像（MRI）技术是否为评估大鼠创伤性脑损伤（TBI）后的神经炎症和药物疗效的敏感生物标志物。我们使大鼠接受可控皮质撞击模型，并使用行为测试、组织学和免疫荧光来评估黄酮类化合物松属素是否提供脑保护并改善功能恢复。最重要的是，我们使用多种非侵入性结构、功能和分子MRI技术来检查在体内是否能检测到与松属素相关的神经保护作用和神经炎症的减轻。在未治疗的TBI大鼠中，在3天时观察到损伤周围区域的脑血流量（CBF）和酰胺质子转移加权（APTw）MRI信号显著增加，这可能归因于胶质反应增强。此外，未治疗的TBI大鼠随时间推移表观扩散系数增加和磁化传递率信号降低可能是由于水肿。用松属素治疗后，在3天时小胶质细胞/巨噬细胞活化减少，这与继发性损伤区域CBF和APTw MRI信号的恢复一致。这些发现表明，松属素为TBI提供脑保护，并且多种MRI信号，尤其是CBF和APTw，是TBI模型中识别和评估神经炎症及药物疗效的敏感生物标志物。
