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

doi:10.1161/STROKEAHA.114.006617

. 2014 Oct;45(10):3092-6.

doi: 10.1161/STROKEAHA.114.006617. Epub 2014 Sep 4.

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

Thomas Gaberel¹, Clement Gakuba¹, Romain Goulay¹, Sara Martinez De Lizarrondo¹, Jean-Luc Hanouz¹, Evelyne Emery¹, Emmanuel Touze¹, Denis Vivien¹, Maxime Gauberti²

Affiliations

¹ From INSERM, INSERM UMR-S U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, GIP Cyceron, University Caen, Caen, France (T.G., C.G., R.G., S.M.D.L., E.E., E.T., D.V., M.G.); and Departments of Neurosurgery (T.G., E.E.), Anesthesiology and Critical Care Medicine (C.G., J.-L.H.), and Neurology (E.T.), Caen University Hospital, Caen, France.
² From INSERM, INSERM UMR-S U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, GIP Cyceron, University Caen, Caen, France (T.G., C.G., R.G., S.M.D.L., E.E., E.T., D.V., M.G.); and Departments of Neurosurgery (T.G., E.E.), Anesthesiology and Critical Care Medicine (C.G., J.-L.H.), and Neurology (E.T.), Caen University Hospital, Caen, France. gauberti@cyceron.fr.

PMID: 25190438
DOI: 10.1161/STROKEAHA.114.006617

Free article

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

Thomas Gaberel et al. Stroke. 2014 Oct.

Free article

. 2014 Oct;45(10):3092-6.

doi: 10.1161/STROKEAHA.114.006617. Epub 2014 Sep 4.

Authors

Thomas Gaberel¹, Clement Gakuba¹, Romain Goulay¹, Sara Martinez De Lizarrondo¹, Jean-Luc Hanouz¹, Evelyne Emery¹, Emmanuel Touze¹, Denis Vivien¹, Maxime Gauberti²

Affiliations

¹ From INSERM, INSERM UMR-S U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, GIP Cyceron, University Caen, Caen, France (T.G., C.G., R.G., S.M.D.L., E.E., E.T., D.V., M.G.); and Departments of Neurosurgery (T.G., E.E.), Anesthesiology and Critical Care Medicine (C.G., J.-L.H.), and Neurology (E.T.), Caen University Hospital, Caen, France.
² From INSERM, INSERM UMR-S U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, GIP Cyceron, University Caen, Caen, France (T.G., C.G., R.G., S.M.D.L., E.E., E.T., D.V., M.G.); and Departments of Neurosurgery (T.G., E.E.), Anesthesiology and Critical Care Medicine (C.G., J.-L.H.), and Neurology (E.T.), Caen University Hospital, Caen, France. gauberti@cyceron.fr.

PMID: 25190438
DOI: 10.1161/STROKEAHA.114.006617

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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.

Keywords: magnetic resonance imaging; subarachnoid hemorrhage; thrombolytic therapy.

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

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

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Cited by 52 articles

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