Brain Barriers Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2321, Australia.
Priority Research Centre for Stroke and Brain Injury, and Priority Research Centre for Brain & Mental Health, University of Newcastle, Callaghan, NSW 2321, Australia.
Int J Mol Sci. 2021 Apr 20;22(8):4280. doi: 10.3390/ijms22084280.
Transient or permanent loss of tissue perfusion due to ischaemic stroke can lead to damage to the neurovasculature, and disrupt brain homeostasis, causing long-term motor and cognitive deficits. Despite promising pre-clinical studies, clinically approved neuroprotective therapies are lacking. Most studies have focused on neurons while ignoring the important roles of other cells of the neurovascular unit, such as astrocytes and pericytes. Astrocytes are important for the development and maintenance of the blood-brain barrier, brain homeostasis, structural support, control of cerebral blood flow and secretion of neuroprotective factors. Emerging data suggest that astrocyte activation exerts both beneficial and detrimental effects following ischaemic stroke. Activated astrocytes provide neuroprotection and contribute to neurorestoration, but also secrete inflammatory modulators, leading to aggravation of the ischaemic lesion. Astrocytes are more resistant than other cell types to stroke pathology, and exert a regulative effect in response to ischaemia. These roles of astrocytes following ischaemic stroke remain incompletely understood, though they represent an appealing target for neurovascular protection following stroke. In this review, we summarise the astrocytic contributions to neurovascular damage and repair following ischaemic stroke, and explore mechanisms of neuroprotection that promote revascularisation and neurorestoration, which may be targeted for developing novel therapies for ischaemic stroke.
由于缺血性中风导致的组织灌注的短暂或永久性丧失可导致神经血管损伤，并破坏脑内环境稳定，导致长期的运动和认知缺陷。尽管有很有前景的临床前研究，但缺乏临床批准的神经保护疗法。大多数研究都集中在神经元上，而忽略了神经血管单元的其他细胞（如星形胶质细胞和周细胞）的重要作用。星形胶质细胞对于血脑屏障的发育和维持、脑内环境稳定、结构支持、脑血流控制和神经保护因子的分泌都很重要。新出现的数据表明，星形胶质细胞在缺血性中风后既发挥有益作用，也发挥有害作用。激活的星形胶质细胞提供神经保护并有助于神经修复，但也分泌炎症调节剂，导致缺血性损伤加重。星形胶质细胞比其他细胞类型对中风病理更具抵抗力，并在对缺血作出反应时发挥调节作用。尽管它们是中风后神经血管保护的一个有吸引力的靶点，但星形胶质细胞在缺血性中风后的这些作用仍不完全清楚。在这篇综述中，我们总结了星形胶质细胞在缺血性中风后对神经血管损伤和修复的贡献，并探讨了促进血管再生和神经修复的神经保护机制，这些机制可能成为开发缺血性中风新疗法的靶点。
