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Stroke, including ischemic stroke and hemorrhagic stroke can cause massive neuronal death and disruption of brain structure, which is followed by secondary inflammatory injury initiated by pro-inflammatory molecules and cellular debris. Phagocytic clearance of cellular debris by microglia, the brain's scavenger cells, is pivotal for neuroinflammation resolution and neurorestoration. However, microglia can also exacerbate neuronal loss by phagocytosing stressed-but-viable neurons in the penumbra, thereby expanding the injury area and hindering neurofunctional recovery. Microglia constantly patrol the central nervous system using their processes to scour the cellular environment and start or cease the phagocytosis progress depending on the "eat me" or "don't eat me'' signals on cellular surface. An optimal immune response requires a delicate balance between different phenotypic states to regulate neuro-inflammation and facilitate reconstruction after stroke. Here, we examine the literature and discuss the molecular mechanisms and cellular pathways regulating microglial phagocytosis, their resulting effects in brain injury and neural regeneration, as well as the potential therapeutic targets that might modulate microglial phagocytic activity to improve neurological function after stroke.

The metabolic reprogramming of peripheral CD4 + T cells that occurs after stroke can lead to imbalanced differentiation of CD4 + T cells, including regulation of T cells, and presents a promising target for poststroke immunotherapy. However, the regulatory mechanism underlying the metabolic reprogramming of peripheral CD4 + T cell remains unknown. In this study, using combined transcription and metabolomics analyses, flow cytometry, and conditional knockout mice, we demonstrate that the receptor for advanced glycation end products (RAGE) can relay the ischemic signal to CD4 + T cells, which underwent acetyl coenzyme A carboxylase 1(ACC1)-dependent metabolic reprogramming after stroke. Furthermore, by administering soluble RAGE (sRAGE) after stroke, we demonstrate that neutralization of RAGE reversed the enhanced fatty acid synthesis of CD4 + T cells and the post-stroke imbalance of Treg/Th17. Finally, we found that post-stroke sRAGE treatment protected against infarct volume and ameliorated functional recovery. In conclusion, sRAGE can serve as a novel immunometabolic modulator that ameliorates ischemic stroke recovery by inhibiting fatty acid synthesis and thus favoring CD4 + T cells polarization toward Treg after cerebral ischemia injury. The above findings provide new insights for the treatment of neuroinflammatory responses after ischemia stroke.

Stroke is followed by an intricate immune interaction involving the engagement of multiple immune cells, including neutrophils. As one of the first responders recruited to the brain, the crucial roles of neutrophils in the ischemic brain damage are receiving increasing attention in recent years. Notably, neutrophils are not homogenous, and yet there is still a lack of full knowledge about the extent and impact of neutrophil heterogeneity. The biological understanding of the neutrophil response to both innate and pathological conditions is rapidly evolving as single-cell-RNA sequencing uncovers overall neutrophil profiling across maturation and differentiation contexts. In this review, we scrutinize the latest research that points to the multifaceted role of neutrophils in different conditions and summarize the regulatory signals that may determine neutrophil diversity. In addition, we list several potential targets or therapeutic strategies targeting neutrophils to limit brain damage following ischemic stroke.

Background: The neurovascular unit (NVU) is emerging as a potential therapeutic target in neurological conditions, such as stroke, brain injury, Alzheimer's disease, and Parkinson's disease; meanwhile, stroke is the second leading cause of death globally. The purpose of the study is to analyze the most influential articles, authors, countries, and topics in the role of NVU in stroke., Methods: The Web of Science (WoS) database was used for bibliometric analysis using the search terms "Stroke" and "Neurovascular unit" on January 1st, 2021. Data were extracted from the WoS database to identify collaborations between authors, countries, organizations, and keywords using VOSviewer (1.6.16 mac). Two bibliometric indicators, the activity index (AI) and category normalized citation impact (CNCI), were computed. The keywords of bursts were also identified by CiteSpace., Results: A total of 770 articles were analyzed by VOSviewer. AIs and CNCIs were computed of the eighteen countries according to VOSviewer co-authorship analysis results. The majority of authors mainly came from the United States and Japan. Romania, Hungary, and Poland have emerged as rising-star countries. In the 100 most-cited articles, the number of citations ranged from 1873 to 69, with a total of 15,758 citations. Most articles were published in 2011 and 2012 (n = 13 each), followed by 2009 (n = 11) and 2013, 2014, and 2015 (n = 8 each). Stroke and Journal of Cerebral Blood Flow and Metabolism were the two top journals. EH Lo from Harvard University/ Massachusetts General Hospital was the top first author and corresponding author. Harvard University/Massachusetts General Hospital was the most productive affiliated institution with 15 publications., Conclusion: There has been growing attention and efforts made in the field of stroke and NVU. The merit of the above findings may help to shape the research policy in ischemic stroke both at the country and institutional level., (© 2021 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Brain perivascular macrophages (PVMs) are attracting increasing attention as this emerging cell population in the brain has multifaced roles in supporting the central nervous system structure, brain development, and maintaining physiological functions. They also widely participate in neurological diseases such as neurodegeneration and ischemic stroke. Moreover, PVMs have been reported to have both beneficial and detrimental effects under different pathological contexts. Advanced research technologies allowed the further in‐depth study of PVMs and revealed novel concepts in their origins, differentiation, and regulatory mechanisms. Deepened understanding of the roles of PVMs in different brain pathological conditions can reveal novel phenotypic changes and regulatory signaling, which might pave the way for the development of novel treatment strategies targeting PVMs. [ABSTRACT FROM AUTHOR]

Postoperative neurological disorders, including postoperative delirium (POD), postoperative cognitive dysfunction (POCD), postoperative covert ischemic stroke, and hemorrhagic stroke, are challenging clinical problems in the emerging aged surgical population. These disorders can deteriorate functional outcomes and long‐term quality of life after surgery, resulting in a substantial social and financial burden to the family and society. Understanding predisposing and precipitating factors may promote individualized preventive treatment for each disorder, as several risk factors are modifiable. Besides prevention, timely identification and treatment of etiologies and symptoms can contribute to better recovery from postoperative neurological disorders and lower risk of long‐term cognitive impairment, disability, and even death. Herein, we summarize the diagnosis, risk factors, prevention, and treatment of these postoperative complications, with emphasis on recent advances and perspectives. [ABSTRACT FROM AUTHOR]