Microglia are the resident immune cells of the central nervous system, playing a crucial role in monitoring and responding to changes within the brain environment. Traditional classification of microglia has been based on their activation status, broadly categorized into two types: M1 and M2. M1 microglia are considered pro-inflammatory, while M2 microglia are viewed as anti-inflammatory. However, it has become increasingly clear that this dichotomous classification fails to capture the diverse and dynamic nature of microglial responses in the brain. Recent advances in single-cell transcriptomics and imaging technologies have demonstrated that microglia comprise a highly heterogeneous population, consisting of distinct subpopulations differentiated by their unique gene expression profiles and functional characteristics. These diverse, context-dependent responses highlight the complexity of microglial biology and challenge the oversimplified M1/M2 framework.

Rather than adhering to a rigid categorization of microglia into discrete groups, it is more appropriate to conceptualize their activation as a continuum, focusing on functional outcomes rather than predetermined classifications. This perspective enables a more nuanced understanding of microglial responses across various brain pathologies and facilitates the development of targeted therapies that leverage the beneficial functions of microglia while mitigating their potentially harmful effects.

The objective of this Research Topic is to consolidate the most recent findings on the diversity of microglia, with particular emphasis on the molecular and cellular mechanisms underlying their functional differences. By elucidating the intricacies of microglial subpopulations and their distinctive functions, we aim to provide a comprehensive understanding of the role of microglia in brain health and disease. This knowledge could ultimately inform the development of novel therapeutic strategies targeting specific microglial subtypes, with the potential to improve outcomes for individuals with neurological conditions.

We welcome submissions on the following topics, but are not limited to:

1. Microglia play a pivotal role in brain development and are essential for maintaining optimal brain function.
2. Microglia perform various functions, including the elimination of excess synapses, the generation of new neurons, and the formation of neural networks.
3. The phenotypes and functions of microglia can change over time and across different brain regions.
4. Microglia have the capacity to alter their phenotype and function to regulate inflammation and facilitate repair following brain injury.
5. The complex mechanisms underlying modifications in gene expression and cell signaling in microglia following brain injuries require further investigation.
6. Microglia are crucial for post-injury debris clearance, maintenance of the blood-brain barrier, and promotion of neuronal growth.
7. The influence of age and sex on microglial responses following brain injury warrants exploration.
8. The potential benefits and complexities of therapeutically targeting microglia are discussed, considering their multifaceted nature and the risk of unintended side effects.

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Frontiers in Immunology

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