Department of Physiology and Galway Neuroscience Centre, School of Medicine, National University of Ireland, Galway, Ireland; CÚRAM-Centre for Research in Medical Devices, National University of Ireland Galway, Galway, Ireland.
Department of Physiology and Galway Neuroscience Centre, School of Medicine, National University of Ireland, Galway, Ireland; CÚRAM-Centre for Research in Medical Devices, National University of Ireland Galway, Galway, Ireland.
Neuroscience. 2021 Jan 15;453:256-265. doi: 10.1016/j.neuroscience.2020.10.034. Epub 2020 Nov 18.
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.
我们研究了在模拟机械取栓的情况下，大脑中动脉闭塞后完全和部分机械再灌注对 MMP-9 表达的影响。使用半球损伤体积和水肿的百分比作为测量指标，部分再灌注减少了 MCA 闭塞引起的脑损伤程度，但保护作用不如完全再灌注明显。使用新鲜冷冻组织的 ELISA 定量，并用灌注固定组织中的免疫荧光进行验证，发现在梗塞组织中观察到 MMP-9 表达增加。MMP-9 在损伤的前颞叶和下纹状体组织以及正常的额皮质中增加，但在海马体中没有观察到明显增加，也没有在未损伤的对侧半球中观察到增加。部分再灌注和完全再灌注均显著降低了区域 MMP 表达。在未再灌注组中，在损伤的脑区观察到最高水平的 MMP-9。MMP-9 表达在受影响组织的微血管和神经元细胞体中均可见。本研究表明，MMP-9 脑水平与再灌注程度相关，相对降低。这些观察结果表明，针对 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治疗药物的理想模型。
