Neuroglia

Introduction: This study investigates how early aging affects the rat brain, focusing on aquaporin-4 and IL-17 levels in the whole brain, as well as glial cell alterations in the hippocampus. The hippocampus, essential for learning and memory, undergoes age-related changes contributing to cognitive decline and neuroinflammation. Glial cells—particularly microglia and astrocytes—are central to these processes. Most research focuses on advanced aging; in this study, we examine early aging effects. Methods: Male Wistar rats (13 weeks and 13 months old) were used. Whole-brain IL-17 and aquaporin-4 levels were assessed by ELISA. Immunohistology targeting GFAP, Iba1, and CD31 was performed on hippocampal sections to assess glial and vascular changes in CA1, CA2/3, and the dentate gyrus (DG). Results: Middle-aged rats brains showed significantly higher IL-17 and aquaporin-4 levels, confirming low-grade inflammation and metabolic alteration. In the hippocampus, microglia, astrocytes, and cerebral microvessels increased in CA2/3, with no significant changes in CA1 or DG. Conclusions: Early aging induces whole-brain neuroinflammation and metabolic changes and region-specific hippocampal alterations, with CA2/3 being particularly susceptible. These findings advance understanding of early brain aging and highlight CA2/3 as a potential target for intervention.

Maternal immune activation (MIA) during pregnancy has been associated with increased risk of fetal loss and neurodevelopmental disorders in offspring. This review summarizes recent findings on the effects of MIA on fetal survival and microglial phenotype. Studies using polyinosinic–polycytidylic acid [poly(I:C)-induced MIA mouse models have revealed the crucial role of interleukin-17A (IL-17A) in mediating these effects. Overexpression of RORγt, a key transcription factor for IL-17A production, enhances poly(I: C)-induced fetal loss, possibly due to increased placental vulnerability. Intraventricular administration of IL-17A in fetal brains activates microglia and alters their localization, particularly in periventricular regions and the medial cortex. These activated microglia may contribute to abnormal synaptic pruning and excessive phagocytosis of neural progenitor cells, potentially leading to long-term neurodevelopmental abnormalities. The insights gained from MIA research have important clinical implications, including the potential for early identification of high-risk pregnancies and the development of novel preventive and therapeutic strategies. Future research should focus on elucidating the roles of other cytokines, determining critical periods of MIA susceptibility, and translating findings to human populations, while carefully considering ethical implications and the need for appropriate risk communication.

Background: Glioblastoma (GBM) remains refractory to chemoradiotherapy. Glial populations—microglia/monocyte-derived macrophages, reactive astrocytes, and the oligodendrocyte lineage—shape both treatment resistance and radiation-related brain injury. Scope: We synthesize how myeloid ontogeny and plasticity, astrocytic hubs (IL-6/STAT3, TGF-β, connexin-43/gap junctions), and oligodendrocyte precursor cells (OPCs)–linked programs intersect with DNA-damage responses, hypoxia-driven metabolism, and extracellular vesicle signaling to support tumor fitness while predisposing normal brain to radiotoxicity. Translational implications: Convergent, targetable pathways (IL-6/JAK–STAT3, TGF-β, chemokine trafficking, DDR/senescence) enable co-design of radiosensitization and neuroprotection. Pragmatic levers include myeloid reprogramming (CSF-1R, CCR2), astrocyte-axis modulation (STAT3, TGF-β, Cx43), and brain-penetrant DDR inhibition (e.g., ATM inhibitors), paired with delivery strategies that raise intratumoral exposure while sparing healthy tissue (focused-ultrasound blood–brain barrier opening, myeloid-targeted dendrimers; Tumor Treating Fields as an approved adjunct therapy). Biomarker frameworks (TSPO-PET, macrophage-oriented MRI radiomics, extracellular vesicle liquid biopsy) can support selection and pharmacodynamic readouts alongside neurocognitive endpoints. Outlook: Timing-aware combinations around radiotherapy and hippocampal/white-matter sparing offer a near-term roadmap for “glia-informed” precision radiotherapy.