Rethinking the pathogenesis of cerebral edema: molecular mechanisms beyond classical models

Abstract

The present article addresses modern aspects of the pathogenesis of cerebral edema (CE), with a focus on novel molecular and cellular mechanisms that extend beyond the classical dichotomy of cytotoxic and vasogenic types. Particular attention is paid to aquaporins, especially AQP4, as key regulators of water exchange in brain tissue, as well as to dysfunction of the glymphatic system, which leads to impaired clearance of interstitial fluid and the accumulation of pathological metabolites. Mitochondrial dysfunction is analyzed as a critical source of energy deficit and free radical generation, further aggravating cellular damage. In addition, cytokine-driven inflammation is highlighted as a background factor that compromises the integrity of neurons and vascular endothelium.

Immune mechanisms are discussed in the context of experimental and clinical data on the involvement of autoantibodies targeting both components of the blood–brain barrier and AQP4, which may contribute to modeling a chronic edematous component and sustain long-term disease progression.