Microglial Activation in High-Grade Gliomas: A Meta-Analysis of IBA1 and CD68 Biomarkers and Their Clinical Implications

Background: High-grade gliomas (HGGs), including glioblastoma, are aggressive brain tumors with poor prognoses despite multimodal therapy. Microglia, the brain’s resident immune cells, play a dual role in HGG progression by either suppressing or promoting tumor growth through neuroinflammatory pathways. However, the relationship between microglial activation markers (IBA1 and CD68) and clinical outcomes remains poorly understood. Hypotheses/Objectives: This meta-analysis aims to evaluate the association between microglial activation (measured by IBA1 and CD68 expression) and clinical outcomes in HGG patients. We hypothesize that elevated IBA1 and CD68 levels correlate with increased neuroinflammation, shorter overall survival, and higher rates of post-surgical complications. Proposed Methods: A systematic literature search will be conducted using PubMed, Scopus, and Web of Science, following PRISMA guidelines. Studies quantifying IBA1 or CD68 in HGG tissue and reporting clinical outcomes (e.g., survival, recurrence, post-operative complications) will be included. Data will be extracted and analyzed using random-effects meta-analytic models to calculate pooled effect sizes and assess heterogeneity (I² statistic). Subgroup analyses will explore tumor grade and treatment history. Future Applications/Directions: Findings from this meta-analysis will clarify the prognostic value of microglial activation in HGGs, potentially guiding neurosurgical strategies and post-operative care. Future research could explore targeted therapies to modulate microglial activity, such as CSF1R inhibitors, to improve patient outcomes.