title: Thrombolysis in experimental cerebral amyloid angiopathy and the risk of secondary intracerebral hemorrhage.
abstract: OBJECTIVE
  Intracerebral hemorrhage (ICH) is the most adverse event of thrombolysis in ischemic stroke. Cerebral amyloid angiopathy increases the risk for spontaneous lobar ICH. Although thrombolysis may be performed in cerebral amyloid angiopathy-affected patients, there is still little knowledge available on the risk for secondary ICH.
  
  
  METHODS
  We investigated the effect of recombinant tissue-type plasminogen activator on experimental ischemic stroke in APP23 transgenic mice (n=18) and wild-type littermates (n=15). Focal ischemic stroke was induced in 26-month-old mice by temporal middle cerebral artery occlusion (filament model), followed by treatment with 10 mg/kg recombinant tissue-type plasminogen activator. Twenty-four hours later, a functional score was assessed and the mice were euthanized for histological analysis. ICH was classified as grades 1 to 3 depending on severity.
  
  
  RESULTS
  The groups did not differ regarding mortality (P=0.67) and functional deficit (P=0.18). Compared with wild-type mice, the APP23 genotype was associated with a higher appearance for ICH in the infarct area (P=0.05). ICH severity grades 2 and 3 correlated significantly with infarct size (P=0.004 and 0.008, respectively).
  
  
  CONCLUSIONS
  The APP23 genotype was not associated with increased mortality or worse functional outcome. Our results suggest an increased risk for ICH in the cerebral amyloid angiopathy-affected brain; however, no ICH was observed outside the ischemic area.
authors.affiliation: From the Department of Neurology, Universitätsmedizin Mannheim (B.R., S.G., E.C., S.M., A.E., M.G.H., M.F.) and Computer Assisted Clinical Medicine, Medical Faculty Mannheim (P.H., L.R.S.), University of Heidelberg, Mannheim, Germany; and Nervous System Department, Novartis Institutes for Biomedical Research, Basel, Switzerland (M.S.) bjoern.reuter@uniklinik-freiburg.de.
authors.forename: Björn
authors.initials: B
authors.lastname: Reuter
authors.affiliation: From the Department of Neurology, Universitätsmedizin Mannheim (B.R., S.G., E.C., S.M., A.E., M.G.H., M.F.) and Computer Assisted Clinical Medicine, Medical Faculty Mannheim (P.H., L.R.S.), University of Heidelberg, Mannheim, Germany; and Nervous System Department, Novartis Institutes for Biomedical Research, Basel, Switzerland (M.S.).
authors.forename: Saskia
authors.initials: S
authors.lastname: Grudzenski
authors.affiliation: From the Department of Neurology, Universitätsmedizin Mannheim (B.R., S.G., E.C., S.M., A.E., M.G.H., M.F.) and Computer Assisted Clinical Medicine, Medical Faculty Mannheim (P.H., L.R.S.), University of Heidelberg, Mannheim, Germany; and Nervous System Department, Novartis Institutes for Biomedical Research, Basel, Switzerland (M.S.).
authors.forename: Eva
authors.initials: E
authors.lastname: Chatzikonstantinou
authors.affiliation: From the Department of Neurology, Universitätsmedizin Mannheim (B.R., S.G., E.C., S.M., A.E., M.G.H., M.F.) and Computer Assisted Clinical Medicine, Medical Faculty Mannheim (P.H., L.R.S.), University of Heidelberg, Mannheim, Germany; and Nervous System Department, Novartis Institutes for Biomedical Research, Basel, Switzerland (M.S.).
authors.forename: Stephen
authors.initials: S
authors.lastname: Meairs
authors.affiliation: From the Department of Neurology, Universitätsmedizin Mannheim (B.R., S.G., E.C., S.M., A.E., M.G.H., M.F.) and Computer Assisted Clinical Medicine, Medical Faculty Mannheim (P.H., L.R.S.), University of Heidelberg, Mannheim, Germany; and Nervous System Department, Novartis Institutes for Biomedical Research, Basel, Switzerland (M.S.).
authors.forename: Anne
authors.initials: A
authors.lastname: Ebert
authors.affiliation: From the Department of Neurology, Universitätsmedizin Mannheim (B.R., S.G., E.C., S.M., A.E., M.G.H., M.F.) and Computer Assisted Clinical Medicine, Medical Faculty Mannheim (P.H., L.R.S.), University of Heidelberg, Mannheim, Germany; and Nervous System Department, Novartis Institutes for Biomedical Research, Basel, Switzerland (M.S.).
authors.forename: Patrick
authors.initials: P
authors.lastname: Heiler
authors.affiliation: From the Department of Neurology, Universitätsmedizin Mannheim (B.R., S.G., E.C., S.M., A.E., M.G.H., M.F.) and Computer Assisted Clinical Medicine, Medical Faculty Mannheim (P.H., L.R.S.), University of Heidelberg, Mannheim, Germany; and Nervous System Department, Novartis Institutes for Biomedical Research, Basel, Switzerland (M.S.).
authors.forename: Lothar R
authors.initials: LR
authors.lastname: Schad
authors.affiliation: From the Department of Neurology, Universitätsmedizin Mannheim (B.R., S.G., E.C., S.M., A.E., M.G.H., M.F.) and Computer Assisted Clinical Medicine, Medical Faculty Mannheim (P.H., L.R.S.), University of Heidelberg, Mannheim, Germany; and Nervous System Department, Novartis Institutes for Biomedical Research, Basel, Switzerland (M.S.).
authors.forename: Matthias
authors.initials: M
authors.lastname: Staufenbiel
authors.affiliation: From the Department of Neurology, Universitätsmedizin Mannheim (B.R., S.G., E.C., S.M., A.E., M.G.H., M.F.) and Computer Assisted Clinical Medicine, Medical Faculty Mannheim (P.H., L.R.S.), University of Heidelberg, Mannheim, Germany; and Nervous System Department, Novartis Institutes for Biomedical Research, Basel, Switzerland (M.S.).
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hennerici
authors.affiliation: From the Department of Neurology, Universitätsmedizin Mannheim (B.R., S.G., E.C., S.M., A.E., M.G.H., M.F.) and Computer Assisted Clinical Medicine, Medical Faculty Mannheim (P.H., L.R.S.), University of Heidelberg, Mannheim, Germany; and Nervous System Department, Novartis Institutes for Biomedical Research, Basel, Switzerland (M.S.).
authors.forename: Marc
authors.initials: M
authors.lastname: Fatar
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D016657:Cerebral Amyloid Angiopathy / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D002543:Cerebral Hemorrhage / Q000139:chemically induced*; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012307:Risk Factors; D020521:Stroke / Q000150:complications / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D010959:Tissue Plasminogen Activator / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: cerebral amyloid angiopathy; cerebral hemorrhage; mice, transgenic; stroke; thrombolytic therapy