Microglia, the resident immune cells of the brain, play a pivotal role in neuroinflammation and brain homeostasis. Recent studies have advanced our understanding of microglial functions in various contexts, particularly in response to injury and disease. For instance, Schafer et al. developed an in vivo neuroimmune organoid model that allows for the study of human microglia phenotypes in a physiologically relevant environment, revealing insights into their maturation and functional capabilities (ref: Schafer doi.org/10.1016/j.cell.2023.04.022/). Choi et al. explored the role of monocyte-derived IL-6 in programming microglia to facilitate cerebrovascular repair following injury, highlighting the importance of microglial activation in angiogenesis (ref: Choi doi.org/10.1038/s41590-023-01521-1/). Furthermore, the study by Mortberg et al. on antisense oligonucleotides (ASOs) demonstrated their potential to modulate RNA in microglia, emphasizing the need for effective targeting to achieve therapeutic outcomes in CNS disorders (ref: Mortberg doi.org/10.1093/nar/). Contradictory findings were noted in the investigation of autophagy's role in microglial engagement with amyloid plaques in Alzheimer's disease, where inhibition of autophagy led to worsened pathology (ref: Choi doi.org/10.1038/s41556-023-01158-0/). Additionally, the impact of neuroinflammation post-COVID-19 was assessed by Braga et al., who utilized PET imaging to measure gliosis in patients with persistent cognitive symptoms, revealing significant elevations in TSPO VT in key brain regions (ref: Braga doi.org/10.1001/jamapsychiatry.2023.1321/).

Microglia are increasingly recognized for their complex roles in neurodegenerative diseases, particularly Alzheimer's disease (AD). Prater et al. conducted a comprehensive transcriptional profiling of human microglia in AD, identifying unique gene regulatory networks that may inform therapeutic strategies (ref: Prater doi.org/10.1038/s43587-023-00424-y/). In a related study, Hua et al. demonstrated that P2X4 receptors in microglia contribute to memory deficits in AD by promoting the degradation of ApoE, a key player in amyloid pathology (ref: Hua doi.org/10.1007/s00018-023-04784-x/). The interplay between microglia and the gut microbiome was also highlighted by Smith et al., who found that microbial modulation could mitigate the effects of environmental stressors on microglial function and behavior (ref: Smith doi.org/10.1038/s41380-023-02108-w/). Contrastingly, the study by Scheepstra et al. focused on the inhibition of cortical gray matter microglia in major depressive disorder, suggesting that microglial dysfunction may underlie the pathophysiology of mood disorders (ref: Scheepstra doi.org/10.1016/j.biopsych.2023.04.020/). These findings collectively underscore the dual nature of microglial responses in neurodegenerative contexts, where they can both exacerbate and mitigate disease processes.

The response of microglia to injury is critical for understanding repair mechanisms in the central nervous system (CNS). Salvador et al. investigated age-dependent immune responses following spinal cord injury, revealing significant differences in microglial activation and myeloid cell infiltration between young and aged mice (ref: Salvador doi.org/10.1016/j.neuron.2023.04.011/). Ruan et al. explored innovative approaches using extracellular vesicles derived from M2 microglia to enhance neural stem cell differentiation at injury sites, highlighting a potential therapeutic avenue for CNS injuries (ref: Ruan doi.org/10.1016/j.apsb.2022.06.007/). Chung et al. provided insights into sepsis-associated encephalopathy, demonstrating that microglia mediate cognitive deficits through C1q-mediated synaptic pruning, thus linking innate immune responses to neuronal damage (ref: Chung doi.org/10.1126/sciadv.abq7806/). Additionally, Wang et al. reported that secreted endogenous macrosomes from microglia can reduce amyloid-beta burden in Alzheimer's models, suggesting a protective role for microglial-derived factors in neurodegenerative pathology (ref: Wang doi.org/10.1126/sciadv.ade0293/). These studies illustrate the multifaceted roles of microglia in injury responses, emphasizing their potential as therapeutic targets for enhancing CNS repair.

Research into microglial aging and sex differences has revealed significant insights into their functional diversity and implications for neurodegenerative diseases. van Olst et al. characterized the immune landscape in aged male mice, identifying systemic factors that contribute to changes in brain immunity and neuronal function (ref: van Olst doi.org/10.1016/j.bbi.2023.05.004/). In a complementary study, Yaqubi et al. utilized single-cell RNA sequencing to analyze microglial transcriptomes across the human lifespan, finding that adult microglia exhibit heightened immune responsiveness compared to prenatal samples (ref: Yaqubi doi.org/10.1186/s12974-023-02809-7/). Cao et al. investigated the modulation of microglial activity by general anesthesia, revealing that anesthetic agents can enhance microglial dynamics, which may influence postoperative outcomes (ref: Cao doi.org/10.1016/j.cub.2023.04.047/). Furthermore, the study by Aly et al. demonstrated that focused ultrasound can enhance gene delivery to microglia, suggesting a novel approach for therapeutic interventions targeting age-related neurodegeneration (ref: Aly doi.org/10.1016/j.jconrel.2023.04.041/). Collectively, these findings underscore the importance of considering age and sex in microglial research, as they may significantly influence neuroinflammatory responses and therapeutic efficacy.

The gut-brain axis has emerged as a critical area of research, particularly regarding the role of microglia in mediating interactions between gut microbiota and brain health. Kim et al. conducted a randomized controlled trial demonstrating that gut microbiota-derived metabolites, specifically indole-3-propionic acid, can mediate the neuroprotective effects of probiotics in elderly individuals, highlighting the potential for dietary interventions to influence microglial function (ref: Kim doi.org/10.1016/j.clnu.2023.04.001/). Wang et al. further explored the effects of Eucommiae cortex polysaccharides on gut microbiota dysbiosis and neuroinflammation, revealing that these compounds can ameliorate depressive-like behaviors in mice subjected to chronic stress (ref: Wang doi.org/10.1016/j.jad.2023.04.117/). Additionally, Kelly et al. reported that inflammatory responses in fetal sheep exposed to LPS were associated with increased microglial activation, suggesting that early-life gut-brain interactions may have lasting effects on neurodevelopment (ref: Kelly doi.org/10.1186/s12974-023-02805-x/). These studies collectively emphasize the intricate relationship between gut microbiota, microglial activity, and neuroinflammation, suggesting that modulating gut health may offer novel therapeutic strategies for neuropsychiatric disorders.

Microglia play a crucial role in immune modulation within the CNS, influencing both neuroinflammatory and neuroprotective responses. Kak et al. investigated the impact of IL-10 production by granulocytes on craniotomy infections, revealing that this immune response can exacerbate infections caused by Staphylococcus aureus, underscoring the importance of microglial and immune cell interactions in post-surgical complications (ref: Kak doi.org/10.1186/s12974-023-02798-7/). Zhang et al. explored the neuroprotective effects of dietary α-ketoglutarate in mouse models of Parkinson's disease, suggesting that dietary interventions can modulate microglial activation and improve cognitive outcomes (ref: Zhang doi.org/10.1007/s00018-023-04807-7/). In a study by Lantz et al., the N-terminal amyloid-β core hexapeptide was shown to reverse gliosis and gliotoxicity in Alzheimer's models, highlighting the potential for targeted therapies to modulate microglial responses in neurodegenerative diseases (ref: Lantz doi.org/10.1186/s12974-023-02807-9/). These findings illustrate the dual roles of microglia in mediating immune responses, emphasizing their potential as therapeutic targets for enhancing neuroprotection and mitigating neuroinflammation.

Microglial interactions with other cell types are critical for understanding their roles in both health and disease. Sun et al. examined the role of TREM2 in glioblastoma, demonstrating that inhibition of TREM2 enhances the antitumor activity of myeloid cells, suggesting a potential therapeutic target for improving immune responses in brain tumors (ref: Sun doi.org/10.1126/sciadv.ade3559/). Zhu et al. investigated the effects of BET inhibitors on retinal degeneration, revealing that these compounds can modulate microglial activation and promote neuroprotection in models of retinal disease (ref: Zhu doi.org/10.1186/s12974-023-02804-y/). Andries et al. highlighted the recruitment of pro-regenerative macrophages to the retina, which can promote axonal regrowth following injury, indicating that microglial interactions with macrophages may facilitate neuronal repair (ref: Andries doi.org/10.1186/s40478-023-01580-3/). Additionally, Alvarez-Sanchez et al. discussed the biological contributors to sex differences in multiple sclerosis progression, emphasizing the role of microglia in mediating immune responses that differ by sex (ref: Alvarez-Sanchez doi.org/10.3389/fimmu.2023.1175874/). These studies collectively underscore the importance of microglial interactions with other cell types in shaping immune responses and influencing disease outcomes.

Microglia are increasingly recognized for their roles in the tumor microenvironment, particularly in glioblastoma. Wang et al. demonstrated that tumor-secreted lactate contributes to an immunosuppressive microenvironment, affecting CD8 T-cell infiltration and highlighting the metabolic interactions between tumor cells and microglia (ref: Wang doi.org/10.3389/fimmu.2023.894853/). Soto-Huelin et al. explored the effects of ellagic acid on lysosomal storage disorders, revealing that enhancing extracellular vesicle secretion can ameliorate disease phenotypes, suggesting a potential therapeutic strategy that involves microglial modulation (ref: Soto-Huelin doi.org/10.1016/j.nbd.2023.106141/). Zhang et al. investigated the effects of siponimod on acute intracerebral hemorrhage, demonstrating that this S1PR modulator can improve outcomes by modulating immune responses in the hemorrhagic brain (ref: Zhang doi.org/10.14336/AD.2022.1102/). These findings collectively emphasize the complex interplay between microglia and the tumor microenvironment, suggesting that targeting microglial functions may offer novel therapeutic avenues for cancer treatment.