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The relationship between cerebral reperfusion and regional expression of matrix metalloproteinase-9 in rat brain following focal cerebral ischemia
Neuroscience ( IF 3.3 ) Pub Date : 2020-11-18 , DOI: 10.1016/j.neuroscience.2020.10.034
A S Douglas 1 , J A Shearer 1 , A Okolo 1 , A Pandit 2 , M Gilvarry 3 , K M Doyle 1
Affiliation  

We investigated the effect of full and partial mechanical reperfusion on MMP-9 expression in rat brain following middle cerebral artery occlusion, mimicking mechanical thrombectomy. Using percentage hemispheric lesion volume and oedema as measures, partial reperfusion reduced extent of brain damage caused by MCA occlusion, but the protective effect was less pronounced than with complete reperfusion. Using ELISA quantification in fresh frozen tissue, confirmed by immunofluorescence in perfusion fixed tissue, increased MMP-9 expression was observed in infarcted tissue. MMP-9 was increased in lesioned tissue of the anterior and posterior temporal cortex and underlying striatal tissue, but also the normal appearing frontal cortex. No significant increase in MMP-9 in the hippocampus was observed, nor in the unlesioned contralateral hemisphere. Both partial reperfusion and full reperfusion reduced the regional MMP expression significantly. The highest levels of MMP-9 were observed in lesioned brain regions in the non-reperfused group. MMP-9 expression was evident in microvessels and in neuronal cell bodies of affected tissue. This study shows that MMP-9 brain levels are reduced relative to the extent of reperfusion. These observations suggest targeting early increases in MMP-9 expression as a possible neuroprotective therapeutic strategy and highlight the rat MCA occlusion model as an ideal model in which to study candidate therapeutics.



中文翻译:

大鼠局灶性脑缺血后脑再灌注与基质金属蛋白酶9区域表达的关系

我们研究了完全和部分机械再灌注对大脑中动脉闭塞后大鼠脑中 MMP-9 表达的影响,模拟机械血栓切除术。以半球病变体积百分比和水肿程度作为衡量标准,部分再灌注降低了由 MCA 闭塞引起的脑损伤程度,但保护作用不如完全再灌注显着。在新鲜冷冻组织中使用 ELISA 定量,通过灌注固定组织中的免疫荧光证实,在梗塞组织中观察到 MMP-9 表达增加。MMP-9 在前、后颞叶皮层和下面的纹状体组织的损伤组织中增加,而且在正常出现的额叶皮层中也增加。没有观察到海马中 MMP-9 的显着增加,也没有在未损伤的对侧半球中观察到。部分再灌注和完全再灌注均显着降低了区域MMP表达。在非再灌注组的受损脑区观察到最高水平的 MMP-9。MMP-9 表达在微血管和受影响组织的神经元细胞体中很明显。该研究表明,MMP-9 脑水平相对于再灌注程度降低。这些观察结果表明,将 MMP-9 表达的早期增加作为一种可能的神经保护治疗策略,并强调大鼠 MCA 闭塞模型是研究候选疗法的理想模型。MMP-9 表达在微血管和受影响组织的神经元细胞体中很明显。该研究表明,MMP-9 脑水平相对于再灌注程度降低。这些观察结果表明,将 MMP-9 表达的早期增加作为一种可能的神经保护治疗策略,并强调大鼠 MCA 闭塞模型是研究候选疗法的理想模型。MMP-9 表达在微血管和受影响组织的神经元细胞体中很明显。该研究表明,MMP-9 脑水平相对于再灌注程度降低。这些观察结果表明,将 MMP-9 表达的早期增加作为一种可能的神经保护治疗策略,并强调大鼠 MCA 闭塞模型是研究候选疗法的理想模型。

更新日期:2020-11-18
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