Impaired Glymphatic Perfusion After Strokes Revealed by Contrast-Enhanced MRI

Abstract

Background and Purpose— The aim of the present study was to investigate the impact of different stroke subtypes on the glymphatic system using MRI. Methods— We first improved and characterized an in vivo protocol to measure the perfusion of the glymphatic system using MRI after minimally invasive injection of a gadolinium chelate within the cisterna magna. Then, the integrity of the glymphatic system was evaluated in 4 stroke models in mice including subarachnoid hemorrhage (SAH), intracerebral hemorrhage, carotid ligature, and embolic ischemic stroke. Results— We were able to reliably evaluate the glymphatic system function using MRI. Moreover, we provided evidence that the glymphatic system was severely impaired after SAH and in the acute phase of ischemic stroke, but was not altered after carotid ligature or in case of intracerebral hemorrhage. Notably, this alteration in glymphatic perfusion reduced brain clearance rate of low-molecular-weight compounds. Interestingly, glymphatic perfusion after SAH can be improved by intracerebroventricular injection of tissue-type plasminogen activator. Moreover, spontaneous arterial recanalization was associated with restoration of the glymphatic function after embolic ischemic stroke. Conclusions— SAH and acute ischemic stroke significantly impair the glymphatic system perfusion. In these contexts, injection of tissue-type plasminogen activator either intracerebroventricularly to clear perivascular spaces (for SAH) or intravenously to restore arterial patency (for ischemic stroke) may improve glymphatic function.

Significance of Understanding Function of Glymphatic System to Manage Practical Clinical Problems of the Elderly

“…This dislocation is similar to the changes found in the aging brain [10]. Impairment of the function of the glymphatic system is also noted after embolic ischemic stroke, however, this damage is transient [18]. Thus, different brain injuries like stroke, subarachnoid bleeding and repetitive traumatic events impair the function of the glymphatic system [1].…”

Understanding the functions and relationships of the glymphatic system and meningeal lymphatics

“…Interestingly, pretreating young wild-type mice with Aβ suppressed glymphatic influx, suggesting that not only is Aβ aggregation a consequence of a breakdown of flow within this pathway, but it may also be an independent cause of glymphatic dysfunction (23). Further, glymphatic impairment is a prominent feature of cerebrovascular disease, including both subarachnoid hemorrhage and multiple microinfarction (24,25). Following traumatic brain injury, reduced clearance of cortical interstitial solute was associated with motor and cognitive neurological deficits (26).…”

Letter by Gaberel et al Regarding Article, “Fibrinolysis for Intraventricular Hemorrhage: An Updated Meta-Analysis and Systematic Review of the Literature”

“…4 We recently demonstrated that this system is severely impaired after SAH, but not after ICH, and may trigger toxic metabolite accumulation within the brain parenchyma. 5 Interestingly, we showed in an experimental SAH model that IVF restores the function of the glymphatic system. Therefore, in addition to macroscopic clot removal, IVF may restore glymphatic circulation in patients presenting IVH secondary to SAH.…”