title: Impaired glymphatic perfusion after strokes revealed by contrast-enhanced MRI: a new target for fibrinolysis?
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gaberel
authors.affiliation: 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.
authors.forename: Clement
authors.initials: C
authors.lastname: Gakuba
authors.affiliation: 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.
authors.forename: Romain
authors.initials: R
authors.lastname: Goulay
authors.affiliation: 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.
authors.forename: Sara
authors.initials: S
authors.lastname: Martinez De Lizarrondo
authors.affiliation: 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.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Hanouz
authors.affiliation: 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.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Emery
authors.affiliation: 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.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Touze
authors.affiliation: 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.
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
authors.affiliation: 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.
authors.forename: Maxime
authors.initials: M
authors.lastname: Gauberti
mesh_terms: D000818:Animals; D002555:Cerebrospinal Fluid / Q000502:physiology; D003287:Contrast Media; D004195:Disease Models, Animal; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D020521:Stroke / Q000134:cerebrospinal fluid* / Q000473:pathology; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid* / Q000473:pathology
chemical_list: D003287:Contrast Media
keywords: magnetic resonance imaging; subarachnoid hemorrhage; thrombolytic therapy