VEGF, AQP4, and IL-6 in the Pathogenesis of Perifocal Edema in Gliomas: Clinical, Radiological, and Morphological Correlations

Perifocal edema (PFE) in gliomas significantly determines neurological deficits, the risk of dislocation, and therapeutic strategies. Complex mechanisms of vascular permeability (VEGF), astrocyte water transport (AQP4), and neuroinflammation (IL-6) are considered key determinants of PFE severity, but their integral clinical, radiological, and morphological correlations have been poorly studied. There is a pressing need to assess the contribution of VEGF, AQP4, and IL-6 to the pathogenesis of PFO in gliomas and their relationship with MR perfusion and diffusion, PFO volume, and clinical outcomes. A single-center retrospective-prospective study of adult patients with glial tumors of different histogenesis was conducted. The study included MRI (T1/T2/FLAIR, DWI/ADC, and, if available, PWI with rCBV/rCBF/MTT), quantitative segmentation of PFO by FLAIR, assessment of midline shift, and immunohistochemistry of VEGF, AQP4 (with an emphasis on polarity and localization), and IL-6. The volume of the PFO, MLS, correlation analysis and clinical associations were measured. Statistics: correlation analysis, multivariate regressions, Kaplan–Meier/Cox model. The following PFO categories were used for stratification in glial tumors: ≤30; 30–60; 60–100; >100 cm³ — a four-step gradation. The primary analysis revealed the following associations: higher VEGF expression with an increase in the volume of the PFO and rCBV, loss of AQP4 polarity with a larger PFO volume, reduced ADC in the perifocal zone and a higher frequency of MLS≥5 mm; Elevated IL-6 — with greater PFO severity, worse KPS scores, and more frequent neurological deficits in the form of irritation and loss symptoms. VEGF, AQP4, and IL-6 form a complementary molecular profile of PFO in glial tumors. Their integrated assessment can improve risk stratification, interpretation of MR perfusion and diffusion imaging, and the choice of anti-edema strategies (including steroid sparing and the targeted approaches being studied). Validation in larger cohorts is required.