The Glymphatic System (En)during Inflammation
Mogensen FL; Delle C; Nedergaard M
International Journal of Molecular Sciences2021
Summary (paraphrased)
This review maps the two-way relationship between neuroinflammation and the glymphatic system. Inflammatory states impair glymphatic flow through perivascular immune-cell accumulation, mislocalization of AQP4 away from astrocytic endfeet (loss of vascular polarity), and reactive changes in astrocytes and microglia. In turn, the resulting buildup of waste and cytokines further drives inflammation, suppresses glymphatic transport, and promotes tissue swelling — a self-reinforcing vicious cycle. The authors highlight astrocytic AQP4 polarization as a dynamic, potentially reversible control point rather than fixed structural damage.
Why it’s in the systems review
This paper supplies the persistence mechanism the axis needs: a self-sustaining neuroinflammation–glymphatic loop that can keep running after the triggering drug is long gone, producing exactly the chronic central symptoms (brain fog, anhedonia) that outlast hormonal recovery. It dovetails with Powers' unpublished theorizing that persistent central symptoms require a central explanation beyond circulating hormone levels, and with the Melcangi-group theme of chronic neuroinflammation as a PFS/PSSD feature. The emphasis on AQP4 polarization as reversible also keeps a therapeutic door open (research-only) for clearance-restoring interventions.
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