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Existing evidence suggests that this system is disrupted by systemic inflammation; however, the pathological characteristics and mechanisms underlying this disruption remain unclear. Near\u2010infrared II imaging reveals an excessive increase in perivascular cerebrospinal fluid (CSF) influx and a reduction in CSF efflux, accompanied by impaired glymphatic clearance within 72\u00a0h in mice intraperitoneally injected with lipopolysaccharide (LPS) at a dose of 5\u00a0mg\u00a0kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    , which does not significantly disrupt the blood\u2010brain barrier. An inverse relationship is observed between cerebral blood flow (CBF) and glymphatic influx trends following LPS challenge. Enhancement of CBF via levosimendan effectively ameliorates glymphatic flux and clearance, but these improvements are abolished by bilateral carotid artery stenosis surgery, indicating that cerebral hypoperfusion mediates LPS\u2010induced glymphatic dysfunction. Furthermore, levosimendan administration attenuates LPS\u2010induced neuroinflammation and neurological deficits. Mechanistically, CBF augmentation prevents the LPS\u2010induced perivascular Aquaporin\u20104 (AQP4) depolarization, whereas the AQP4 inhibitor TGN\u2010020 blocks its beneficial effects on both amyloid\u2010\u03b2 clearance and neuroinflammation suppression, confirming AQP4's pivotal role. Behaviorally, levosimendan ameliorates LPS\u2010induced neurological deficits. These findings establish cerebral hypoperfusion as a key mediator of systemic inflammation\u2010induced glymphatic dysfunction, revealing a promising therapeutic avenue for sepsis\u2010associated encephalopathy.\n                  <\/jats:p>","DOI":"10.1002\/advs.202503576","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T03:28:07Z","timestamp":1759721287000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Potentiating Cerebral Perfusion Normalizes Glymphatic Dynamics in Systemic Inflammation"],"prefix":"10.1002","volume":"12","author":[{"given":"Ruoyu","family":"Zhao","sequence":"first","affiliation":[{"name":"Stroke Center Department of Neurology The First Hospital of Jilin University  Chang Chun 130021 P. R. 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