Impaired glymphatic perfusion after strokes revealed by contrast-enhanced MRI: a new target for fibrinolysis?

T Gaberel, C Gakuba, R Goulay, SM De Lizarrondo… - Stroke, 2014 - Am Heart Assoc
T Gaberel, C Gakuba, R Goulay, SM De Lizarrondo, JL Hanouz, E Emery, E Touze, D Vivien…
Stroke, 2014Am Heart Assoc
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 …
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.
Am Heart Assoc