Cisternal Contrast-Enhanced MRI Reveals Post-Stroke Glymphatic Impairment and Compensatory Metabolic Waste Clearance via Microglia/Macrophages.

Recent studies have shown that the glymphatic system plays a crucial role in driving hyperacute edema after ischemic stroke. This has sparked interest in understanding how this system changes in later phases of ischemic stroke. In this study, we utilized cisternal contrast-enhanced magnetic resonance imaging (CE-MRI) and immunofluorescence staining to investigate glymphatic system alterations at subacute and chronic phases of ischemic stroke. Middle cerebral artery occlusion (MCAO) for 90 min in Sprague-Dawley rats was used to mimic ischemic stroke. A total of 20 rats were randomly divided into four groups: sham group, MCAO 1-week group, MCAO 2-week group, and MCAO 2-month group. Our results showed the glymphatic system was spatially and temporally heterogeneously impaired in the peri-infarct area at subacute phase, even lasting for chronic phase. Specially, we found retention of contrast after cisternal CE-MRI in the infarct core and peri-infarct area at subacute phase of ischemic stroke, which corresponded to the distribution of microglia/macrophages. Our results indicated that ischemic stroke contributed to long-term glymphatic impairment and waste retention, and cisternal CE-MRI delayed enhancement could reflect the retention of waste and activation of microglia/macrophages in this process. These findings suggest cisternal CE-MRI might be a useful tool for investigating the interaction between the glymphatic system and microglia/macrophages in waste clearance and neuroinflammation after brain insult.