Björn Reuter1, Saskia Grudzenski2, Eva Chatzikonstantinou2, Stephen Meairs2, Anne Ebert2, Patrick Heiler2, Lothar R Schad2, Matthias Staufenbiel2, Michael G Hennerici2, Marc Fatar2. 1. 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. 2. 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.).
Abstract
BACKGROUND AND PURPOSE: 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.
BACKGROUND AND PURPOSE: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: Friedrich Wetterling; Eva Chatzikonstantinou; Laurent Tritschler; Stephen Meairs; Marc Fatar; Lothar R Schad; Saema Ansar Journal: BMC Neurosci Date: 2016-12-07 Impact factor: 3.288
Authors: Björn Reuter; Alexander Venus; Patrick Heiler; Lothar Schad; Anne Ebert; Michael G Hennerici; Saskia Grudzenski; Marc Fatar Journal: Front Aging Neurosci Date: 2016-07-08 Impact factor: 5.750
Authors: Björn Reuter; Alexander Venus; Saskia Grudzenski; Patrick Heiler; Lothar Schad; Matthias Staufenbiel; Michael G Hennerici; Marc Fatar Journal: Int J Mol Sci Date: 2016-01-19 Impact factor: 5.923