ABSTRACT Stroke remains the leading cause of long-term disability worldwide with significant long-term sequalae. However, there is no highly effective treatment to enhance post stroke recovery despite extensive efforts in exploring rehabilitative therapies. Neurorehabilitation is recognized as the cornerstone of functional restoration therapy in stroke, where treatments are focused on neuroplastic regulation to reverse neural structural disruption and improve neurofunctional networks. Post stroke neuroplasticity changes begin within hours of symptom onset and reaches a plateau by three to four weeks within the global brain in animal studies. It plays a determining role in spontaneous stroke recovery. Microglia are immediately activated following cerebral ischemia, which has been found both proximally to the primary ischemic injury and at the remote brain regions which have functional connections to the primary injury area. Microglia exhibit different activation profiles based on the microenvironment and adaptively switch their phenotypes in a spatiotemporal manner in response to the brain injuries. Microglia activation coincides with neuroplasticity after stroke, which provides the fundamental base for the microglia-mediated inflammatory responses involved in the entire neural network rewiring and brain repair. Microglial activation exerts important effects on spontaneous recovery after stroke, including structural and functional reestablishment of neurovascular networks, neurogenesis, axonal remodeling, blood vessel regeneration, etc. In this review, we focus on the crosstalk between microglia activation and endogenous neuroplasticity, with a special focus on the plastic alterations in whole brain network and their implications for structural and functional restoration after stroke. We then summarize recent advances in the impacts of microglial phenotype polarization on brain plasticity, trying to discuss the potential efficacy of microglia based extrinsic restorative interventions in promoting post stroke recovery.

中文翻译：

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小胶质细胞调节在依赖于脑可塑性的中风恢复中的作用的新见解

摘要 中风仍然是全球长期残疾的主要原因，并具有显着的长期后遗症。然而，尽管在探索康复疗法方面付出了大量努力，但仍没有高效的治疗方法来促进中风后的恢复。神经康复被公认为中风功能恢复治疗的基石，治疗的重点是神经可塑性调节，以逆转神经结构破坏并改善神经功能网络。在动物研究中，中风后神经可塑性变化在症状出现后数小时内开始，并在 3 到 4 周内在全球大脑内达到平稳状态。它在中风自发恢复中起着决定性的作用。小胶质细胞在脑缺血后立即被激活，它已在原发性缺血性损伤的近端和与原发性损伤区域具有功能连接的偏远脑区中发现。小胶质细胞根据微环境表现出不同的激活特征，并以时空方式自适应地转换其表型以响应脑损伤。小胶质细胞激活与中风后的神经可塑性相吻合，这为参与整个神经网络重新布线和大脑修复的小胶质细胞介导的炎症反应提供了基础。小胶质细胞激活对卒中后自发恢复具有重要影响，包括神经血管网络的结构和功能重建、神经发生、轴突重塑、血管再生等。我们关注小胶质细胞激活和内源性神经可塑性之间的串扰，特别关注整个大脑网络的可塑性改变及其对中风后结构和功能恢复的影响。然后，我们总结了小胶质细胞表型极化对大脑可塑性的影响的最新进展，试图讨论基于小胶质细胞的外在修复干预在促进中风后恢复方面的潜在功效。