As oligodendrocyte precursor cells (OPCs) are vulnerable to ischemia, their differentiation to oligodendrocytes (OLG) is impaired in chronic cerebral hypoperfusion. Astrocyte–OLG interaction is important for white matter homeostasis. Recently, reactive astrocytes were separated into two types, A1 (cytotoxic) and A2 (neurotrophic). However, their role in prolonged cerebral hypoperfusion remains unclear. We analyzed the effects of interaction between A1–A2 astrocytes and OPC–OLG under hypoperfusion, focusing on mitochondrial migration. As an in vivo model, chronic hypoperfusion model mice were created by bilateral common carotid artery stenosis (BCAS) using microcoils. As a matching in vitro study, rat primary cells were cocultured with a nonlethal concentration of CoCl₂. At 28 days after hypoperfusion, the number of OPC and astrocytes increased, whereas that of OLG decreased. Increased astrocytes were mainly A1‐like astrocytes; however, the number of A2‐like type decreased. In cell culture, OPC differentiation was interrupted under mimic chronic ischemia, but improved after astrocyte‐conditioned medium (ACM) was added. However, injured‐ACM was unable to improve OPC maturation. Incubation with CoCl₂ changed astrocytes from A2‐like to A1‐like, and mitochondrial migration was also reduced. A Trkβ agonist was able to maintain astrocytes from A1‐like to A2‐like even under hyperperfused conditions, and aided in OPC maturation and memory impairment via mitochondrial migration and drug effects in cell culture study and BCAS model. The reduction of A1‐like astrocytes protects against white matter injury. Trkβ agonists may play an important role in the impairment under chronic ischemic conditions. Mitochondrial migration may be a broad therapeutic strategy for cerebrovascular diseases.

中文翻译：

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A1/A2 星形胶质细胞对少突胶质细胞系细胞抗长期脑低灌注白质损伤的影响。

由于少突胶质细胞前体细胞 (OPC) 易受缺血影响，因此它们向少突胶质细胞 (OLG) 的分化在慢性脑灌注不足中受损。星形胶质细胞-OLG 相互作用对于白质稳态很重要。最近，反应性星形胶质细胞分为两种类型，A1（细胞毒性）和 A2（神经营养）。然而，它们在长期脑灌注不足中的作用仍不清楚。我们分析了低灌注下 A1-A2 星形胶质细胞和 OPC-OLG 之间相互作用的影响，重点是线粒体迁移。作为体内模型，使用微线圈通过双侧颈总动脉狭窄 (BCAS) 创建慢性低灌注模型小鼠。作为匹配的体外研究，大鼠原代细胞与非致死浓度的 CoCl ₂共培养. 低灌注后28天，OPC和星形胶质细胞数量增加，而OLG数量减少。增多的星形胶质细胞主要是A1样星形胶质细胞；然而，A2-like 类型的数量减少了。在细胞培养中，OPC 分化在模拟慢性缺血下被中断，但在添加星形胶质细胞条件培养基 (ACM) 后有所改善。然而，受伤的 ACM 无法改善 OPC 的成熟。用 CoCl ₂孵育将星形胶质细胞从 A2 样变为 A1 样，并且线粒体迁移也减少了。即使在高灌注条件下，Trkβ 激动剂也能够维持星形胶质细胞从 A1 样到 A2 样，并通过细胞培养研究和 BCAS 模型中的线粒体迁移和药物效应帮助 OPC 成熟和记忆障碍。A1 样星形胶质细胞的减少可防止白质损伤。Trkβ 激动剂可能在慢性缺血条件下的损伤中发挥重要作用。线粒体迁移可能是脑血管疾病的广泛治疗策略。