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<p>Cognitive impairment encompasses a range of clinical syndromes resulting from various brain disorders. Among these, Alzheimer’s disease and related dementias, Parkinson’s disease, and stroke represent the most prevalent and significant cerebrovascular conditions that impact cognitive function and lead to neurodegenerative damage. Microglia, serving as the principal immune regulators within brain tissue, exhibit diverse phenotypes, including M1 and M2, in response to inflammatory environments, thereby collectively contributing to the restoration of homeostasis. However, under sustained stimulation, microglia undergo cell death and release inflammatory factors through different mechanisms of cell death, thereby influencing the prognosis of cerebrovascular diseases. Although there is a growing recognition of the regulatory role of microglial phenotypic transformation in the progression of cerebrovascular diseases, research remains insufficient regarding the developmental processes of these diseases following the death of microglial cells with varying phenotypes. This article centres on cerebrovascular disease-induced cognitive impairment as its primary focus. It provides a comprehensive review of common acute cerebrovascular diseases, such as ischemic stroke, alongside neurodegenerative conditions including Alzheimer’s disease, Parkinson’s disease, and vascular dementia. The discussion extends to the common phenotypes of microglia and their impact on cerebrovascular diseases. Additionally, the article explores how inflammatory cell death mechanisms of microglia, namely necroptosis, pyroptosis, ferroptosis, and autophagy, regulate disease progression, thereby providing insights for future research on the role of microglia in cerebrovascular pathology.</p>

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Regulatory cell death of microglia in common cerebrovascular diseases: mechanism, heterogeneity and therapeutic significance

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月5日

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  • Jialin Cheng,
  • Chuxin Zhang,
  • Yingping He,
  • Xin Lan,
  • Yuxiao Zheng,
  • Jinhua Han,
  • Jiaming Li,
  • Yang Zhao,
  • Bomin Zhang,
  • Sicheng Feng,
  • Fafeng Cheng,
  • Qingguo Wang,
  • Changxiang Li,
  • Xueqian Wang

摘要

Cognitive impairment encompasses a range of clinical syndromes resulting from various brain disorders. Among these, Alzheimer’s disease and related dementias, Parkinson’s disease, and stroke represent the most prevalent and significant cerebrovascular conditions that impact cognitive function and lead to neurodegenerative damage. Microglia, serving as the principal immune regulators within brain tissue, exhibit diverse phenotypes, including M1 and M2, in response to inflammatory environments, thereby collectively contributing to the restoration of homeostasis. However, under sustained stimulation, microglia undergo cell death and release inflammatory factors through different mechanisms of cell death, thereby influencing the prognosis of cerebrovascular diseases. Although there is a growing recognition of the regulatory role of microglial phenotypic transformation in the progression of cerebrovascular diseases, research remains insufficient regarding the developmental processes of these diseases following the death of microglial cells with varying phenotypes. This article centres on cerebrovascular disease-induced cognitive impairment as its primary focus. It provides a comprehensive review of common acute cerebrovascular diseases, such as ischemic stroke, alongside neurodegenerative conditions including Alzheimer’s disease, Parkinson’s disease, and vascular dementia. The discussion extends to the common phenotypes of microglia and their impact on cerebrovascular diseases. Additionally, the article explores how inflammatory cell death mechanisms of microglia, namely necroptosis, pyroptosis, ferroptosis, and autophagy, regulate disease progression, thereby providing insights for future research on the role of microglia in cerebrovascular pathology.