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小鼠不同品系在缺血性中风后脑损伤大小的修复及神经功能障碍的恢复存在差异:使用新型缺血性中风模型进行评估

Repair of brain damage size and recovery of neurological dysfunction after ischemic stroke are different between strains in mice: evaluation using a novel ischemic stroke model.

作者信息

Matano Yasuki, Nojiri Yuuto, Nomura Mizuki, Masuda Akira, Moriike Yuuki, Suzuki Yasuhiro, Umemura Kazuo, Nagai Nobuo

机构信息

Laboratory of Animal Physiology, Division of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.

School of Pharmaceutical Sciences, Faculty of Pharmacy, Ohu University, 31-1 Sankaku-do, Tomita-cho, Kohriyama, Fukushima 963-8611, Japan.

出版信息

Exp Anim. 2021 Aug 6;70(3):344-354. doi: 10.1538/expanim.20-0182. Epub 2021 Mar 16.

Abstract

In the current study, we established a novel murine ischemic brain damage model using a photochemical reaction to evaluate the recovery of neurological dysfunction and brain repair reactions. In this model, reproducible damage was induced in the frontal lobe of the cortex, which was accompanied by neurological dysfunction. Sequential changes in damage size, microglial accumulation, astrocyte activation, and neurological dysfunction were studied in C57BL/6J and BALB/c mouse strains. Although the initial size of damage was comparable in both strains, the extent of damage was later reduced to a greater extent in C57BL/6J mice than that in BALB/c mice. In addition, C57BL/6J mice showed later edema clearance until day 7, less microglial accumulation, and relatively more astrocyte activation on day 7. Neurologic dysfunction was evaluated by three behavioral tests: the von Frey test, the balance beam test, and the tail suspension test. The behavioral abnormalities evaluated by these tests were remarkable following the induction of damage and recovered by day 21 in both strains. However, the abnormalities were more prominent and the recovery was later in C57BL/6J mice. These findings demonstrate that our novel ischemic stroke model is useful for evaluating brain repair reactions and the recovery of neurological dysfunction in mice with different genetic backgrounds. In addition, we found that both the brain repair reactions and the recovery of neurological dysfunction after comparable ischemic brain damage varied between strains; in that, they both occurred later in C57BL/6J mice.

摘要

在本研究中,我们利用光化学反应建立了一种新型的小鼠缺血性脑损伤模型,以评估神经功能障碍的恢复情况和脑修复反应。在该模型中,可在皮质额叶诱导出可重复性损伤,并伴有神经功能障碍。我们研究了C57BL/6J和BALB/c小鼠品系中损伤大小、小胶质细胞聚集、星形胶质细胞活化和神经功能障碍的序贯变化。虽然两个品系的初始损伤大小相当,但C57BL/6J小鼠的损伤程度在后期比BALB/c小鼠有更大程度的减轻。此外,C57BL/6J小鼠在第7天前水肿清除较晚,小胶质细胞聚集较少,且在第7天星形胶质细胞活化相对较多。通过三种行为测试评估神经功能障碍:von Frey测试、平衡木测试和尾悬挂测试。这些测试评估的行为异常在损伤诱导后很明显,且在两个品系中均在第21天恢复。然而,这些异常在C57BL/6J小鼠中更为突出,恢复也更晚。这些发现表明,我们的新型缺血性中风模型可用于评估不同遗传背景小鼠的脑修复反应和神经功能障碍的恢复情况。此外,我们发现,在相当的缺血性脑损伤后,脑修复反应和神经功能障碍的恢复在不同品系之间存在差异;具体而言,它们在C57BL/6J小鼠中均发生得较晚。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0673/8390305/cea7ea25486e/expanim-70-344-g001.jpg

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