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

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. This literature search selected two major international mainstream academic databases, PubMed and Web of Science, to include high-quality original research and review papers in the field. Based on the research topic of this study, a combination of subject terms and free words was used to conduct a search of articles from January 2000 to June 2026. The English search keywords were: microglia, phenotype, necroptosis, pyroptosis, ferroptosis, autophagy, PANoptosis, Alzheimer's disease, Parkinson's disease, vascular dementia, ischemic stroke, cytokines, signaling pathway. Academic literature that was officially published and had the complete full text available was selected. Subsequently, a preliminary screening was conducted by reading the titles and abstracts, and those obviously not related to the topic were eliminated. Finally, a re-screening was carried out by reading the full texts, and the final list of included literature was determined strictly according to the inclusion and exclusion criteria, ensuring the scientificity, representativeness and rigor of the literature materials of this review.