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In Vitro Model for Ischemic Stroke: Functional Analysis of Vascular Smooth Muscle Cells
Cellular and Molecular Neurobiology ( IF 4 ) Pub Date : 2021-05-25 , DOI: 10.1007/s10571-021-01103-5
Melissa Mariana 1, 2 , Claudio Roque 1, 2 , Graça Baltazar 1, 2 , Elisa Cairrao 1, 2
Affiliation  

The Neurovascular Unit (NVU) is formed by vascular and neural cells controlling the cerebral hyperaemia. All the components are anatomically and functionally linked to each other, resulting in a highly efficient regulation of the cerebral blood flow, which, when interrupted, can lead to stroke. An ischemic stroke (IS) is the most common type of stroke with high rates of morbidity, mortality and disability. Therefore, it is of extreme importance to protect the functional and structural integrity of the NVU in patients with IS, understanding the mechanisms involved and how it affects each component of the NVU. Thus, the aim of this work is to analyse how the vascular smooth muscle cells from the rat middle cerebral artery function/react after an ischemic event. To mimic this event, primary cortical cultures were challenged to oxygen and glucose deprivation (OGD) for 4 h and 6 h, and the smooth muscle cells (SMCs) contractility was analysed after exposure to different media previously conditioned by the cortical cultures upon reperfusion. The results show a dual effect on the SMCs response to the vasorelaxant agent, only for cells exposed to the reperfusion media conditioned by neuron-glia cultures challenged by OGD, leading to increased relaxation of the SMCs for OGD 4 h, whereas for OGD 6 h the effect is reversed leading to contraction of the SMCs. These differences demonstrate that the astrocytes mediate the vasoactive response of vascular smooth muscle by releasing factors into the reperfusion medium, and the hypoxia time is fundamental for a beneficial/harmful response by the vascular smooth muscle.



中文翻译:

缺血性中风的体外模型:血管平滑肌细胞的功能分析

神经血管单元 (NVU) 由控制脑充血的血管和神经细胞组成。所有组件在解剖学和功能上都相互关联,从而高效调节脑血流,如果中断,可能导致中风。缺血性中风 (IS) 是最常见的中风类型,发病率、死亡率和残疾率都很高。因此,保护​​ IS 患者 NVU 的功能和结构完整性,了解所涉及的机制以及它如何影响 NVU 的每个组成部分是极其重要的。因此,这项工作的目的是分析来自大鼠大脑中动脉的血管平滑肌细胞在缺血事件后如何发挥功能/反应。为了模仿这个事件,原代皮层培养物受到氧和葡萄糖剥夺 (OGD) 的挑战 4 小时和 6 小时,并且在暴露于先前由再灌注时皮层培养物调节的不同培养基后分析平滑肌细胞 (SMC) 的收缩性。结果显示对 SMC 对血管舒张剂的反应有双重影响,仅对于暴露于由 OGD 挑战的神经元胶质细胞培养物调节的再灌注培养基的细胞,导致 OGD 4 小时的 SMC 松弛增加,而 OGD 6 小时效果相反,导致 SMC 收缩。这些差异表明星形胶质细胞通过将因子释放到再灌注介质中来介导血管平滑肌的血管活性反应,而缺氧时间是血管平滑肌产生有益/有害反应的基础。

更新日期:2021-05-25
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