Glymphatic dysfunction and cerebral edema: A transport-based framework, evidence, and therapeutic implications
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GRAPHICAL ABSTRACT
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PUBLIC SUMMARY
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Cerebral edema after stroke, bleeding, or trauma can worsen injury and threaten life.
The glymphatic system is a brain-wide fluid transport network that may influence edema over time.
Studies suggest that early fluid entry can drive swelling, while poor clearance can make it last.
Aquaporin-4 may promote fluid entry or removal, depending on injury type and timing.
More human studies are needed before treatments can be recommended.
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ABSTRACT
Cerebral edema is a major cause of secondary injury after acute brain insults. Classical categories describe the compartment of water accumulation and the integrity of relevant barriers, but they less directly capture fluid sources, transport routes, and clearance over time. The glymphatic system supports cerebrospinal fluid (CSF)-interstitial fluid (ISF) exchange and may influence brain water movement. Here, we critically evaluate evidence linking glymphatic dysfunction to edema after ischemic, hemorrhagic, and traumatic brain injury (TBI). Building on the term introduced by Eide and Ringstad, we use glymphatic-stagnated edema as a provisional transport-based framework to organize evidence across injury types, temporal phases, and transport dysfunctions. We distinguish aquaporin-4 (AQP4) abundance from perivascular polarization and establish a hierarchical evidence framework ranging from direct tracer imaging to clinical imaging studies. We also identify injury-specific transport patterns: hyperacute CSF entry in ischemia, intervention-responsive efflux failure in TBI, and context-dependent AQP4 effects. Given that the evidence is predominantly preclinical, human validation requires multicenter studies pairing serial transport measures with independent edema quantification. We outline testable predictions and a translational roadmap for evaluating glymphatic-directed interventions in neurocritical care.-
Keywords:
- Glymphatic system /
- cerebral edema /
- cerebrospinal fluid /
- aquaporin-4 /
- astrocyte
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Wang Z., Zhang J., Dong Q., et al. (2026). Glymphatic dysfunction and cerebral edema: A transport-based framework, evidence, and therapeutic implications. The Innovation Neurology 1:100014. https://doi.org/10.59717/j.xinn-tine.2026.100014
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Wang Z., Zhang J., Dong Q., et al. (2026). Glymphatic dysfunction and cerebral edema: A transport-based framework, evidence, and therapeutic implications. The Innovation Neurology 1:100014. https://doi.org/10.59717/j.xinn-tine.2026.100014
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Figure 1.
Overview of glymphatic influx and efflux pathways in brain water homeostasis
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Figure 2.
AQP4 localization at brain-fluid interfaces relevant to perivascular and periventricular transport
