Ying Bai

Astrocytes, the most prevalent glial cells in the central nervous system (CNS), play crucial roles in maintaining CNS homeostasis and responding to various pathological stimuli. They play key roles in neural development, neurotransmission, neuroinflammation, metabolic support, and tissue repair. Recent advancements in single‐cell sequencing have revealed the remarkable heterogeneity of astrocytes, with distinct subpopulations differentially contributing to disease progression in neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, ischemic stroke, intracerebral hemorrhage, and multiple sclerosis. In addition, they play an important role in various behavioral neuropsychiatric disorders. This review highlights the dual roles of astrocytes in disease progression, driven by their diverse molecular profiles and functions. It outlines the key molecular mechanisms underlying astrocyte heterogeneity and their impact on neuroinflammation, neuronal support, and ionic balance regulation. Additionally, the review discusses potential therapeutic strategies targeting astrocytes to modulate these processes, aiming to improve treatment outcomes in neurological diseases. By elucidating the specific roles of astrocyte subsets in disease, this review seeks to advance the development of precision medicine for astrocyte‐related neurological disorders.

Astrocytes, characterized by complex spongiform morphology, participate in various physiological processes, and abnormal changes in their calcium (Ca²⁺) signaling are implicated in central nervous system disorders. However, medications targeting the control of Ca²⁺ have fallen short of the anticipated therapeutic outcomes in clinical applications. This underscores the fact that our comprehension of this intricate regulation of calcium ions remains considerably incomplete. In recent years, with the advancement of Ca²⁺ labeling, imaging, and analysis techniques, Ca²⁺ signals have been found to exhibit high specificity at different spatial locations within the intricate structure of astrocytes. This has ushered the study of Ca²⁺ signaling in astrocytes into a new phase, leading to several groundbreaking research achievements. Despite this, the comprehensive understanding of astrocytic Ca²⁺ signaling and their implications remains challenging area for future research.

Neuroinflammation is acknowledged as a pivotal pathological event after cerebral ischemia. However, there is limited knowledge of the molecular and spatial characteristics of nonneuronal cells, as well as of the interactions between cell types in the ischemic brain. Here, we used spatial transcriptomics to study the ischemic hemisphere in mice after stroke and sequenced the transcriptomes of 19,777 spots, allowing us to both visualize the transcriptional landscape within the tissue and identify gene expression profiles linked to specific histologic entities. Cell types identified by single-cell RNA sequencing confirmed and enriched the spatial annotation of ischemia-associated gene expression in the peri-infarct area of the ischemic hemisphere. Analysis of ligand-receptor interactions in cell communication revealed galectin-9 to cell-surface glycoprotein CD44 (LGALS9-CD44) as a critical signaling pathway after ischemic injury and identified microglia and macrophages as the main source of galectins after stroke. Extracellular vesicle–mediated Lgals9 delivery improved the long-term functional recovery in photothrombotic stroke mice. Knockdown of Cd44 partially reversed these therapeutic effects, inhibiting oligodendrocyte differentiation and remyelination. In summary, our study provides a detailed molecular and cellular characterization of the peri-infact area in a murine stroke model and revealed Lgals9 as potential treatment target that warrants further investigation.

Circular RNAs (circRNAs) are a class of regulatory non-coding RNAs characterized by the presence of covalently closed ends. A growing body of evidence suggests that circRNAs play important roles in physiology and pathology. In particular, accumulating data on circRNA functions in various central nervous system (CNS) diseases and their correlations indicate that circRNAs are critical contributors to the onset and development of brain disorders. In this review, we focus on the regulatory and functional roles of circRNAs in CNS diseases, highlighting their diagnostic and therapeutic potential, with the aim of providing new insights into CNS diseases.

Circular RNAs (circRNAs) are a subtype of non-coding RNAs and contribute to the various central nervous system (CNS) diseases. However, microglia apoptosis which is regulated by circRNAs in major depressive disorder (MDD) is incompletely clear. Herein, we have shown that the circular RNA DYM (circDYM) binds to the transcription factor CEBPB, thereby releasing repression of CEBPB target gene ZC3H4 transcription. The result of our study provides new insights in function of circDYM to microglia apoptosis in depression. Taken together, we identify that circRNA drives neuroinflammation and serves as a new potential target for therapy of depression.

Clinical treatments for ischemic stroke are limited. At present, neural stem cell (NSC) therapy is considered a promising method for treating ischemic stroke. However, the behavior of transplanted NSCs remains ambiguous. Herein, we report the feasibility of superparamagnetic iron oxide labeling for long-time magnetic resonance imaging to track transplanted NSCs in a transient middle cerebral artery occlusion model. According to our studies, in vivo monitoring of transplanted NSCs during ischemic stroke in the current work may provide another insight into the tracking strategy of transplanted NSCs, thereby advancing NSC-based therapy toward clinical application.

Ischemic stroke is a major cause of death and disability worldwide. There is almost no effective treatment for this disease. Therefore, developing effective treatment for ischemic stroke is urgently needed. Efficient delivery of therapeutic drugs to ischemic sites remained a great challenge for improved treatment of strokes. In recent years, hydrogel-based strategies have been widely investigated for new and improved therapies. They have the advantage of delivering therapeutics in a controlled manner to the poststroke sites, aiming to enhance the intrinsic repair and regeneration. In this review, we discuss the pathophysiology of stroke and the development of injectable hydrogels in the application of both stroke treatment and neural tissue engineering. We also discuss the prospect and the challenges of hydrogels in the treatment of ischemic strokes.