title: Non-invasive diagnostic biomarkers for estimating the onset time of permanent cerebral ischemia.
abstract: The treatments for ischemic stroke can only be administered in a narrow time-window. However, the ischemia onset time is unknown in ~30% of stroke patients (wake-up strokes). The objective of this study was to determine whether MR spectra of ischemic brains might allow the precise estimation of cerebral ischemia onset time. We modeled ischemic stroke in male ICR-CD1 mice using a permanent middle cerebral artery filament occlusion model with laser Doppler control of the regional cerebral blood flow. Mice were then subjected to repeated MRS measurements of ipsilateral striatum at 14.1 T. A striking initial increase in γ-aminobutyric acid (GABA) and no increase in glutamine were observed. A steady decline was observed for taurine (Tau), N-acetyl-aspartate (NAA) and similarly for the sum of NAA+Tau+glutamate that mimicked an exponential function. The estimation of the time of onset of permanent ischemia within 6 hours in a blinded experiment with mice showed an accuracy of 33±10 minutes. A plot of GABA, Tau, and neuronal marker concentrations against the ratio of acetate/NAA allowed precise separation of mice whose ischemia onset lay within arbitrarily chosen time-windows. We conclude that (1)H-MRS has the potential to detect the clinically relevant time of onset of ischemic stroke.
authors.affiliation: Department of Clinical Neurosciences, Neurology Service, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Carole
authors.initials: C
authors.lastname: Berthet
authors.affiliation: 1] Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland [2] Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
authors.forename: Lijing
authors.initials: L
authors.lastname: Xin
authors.affiliation: Department of Clinical Neurosciences, Neurology Service, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Lara
authors.initials: L
authors.lastname: Buscemi
authors.affiliation: Department of Clinical Neurosciences, Neurology Service, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Corinne
authors.initials: C
authors.lastname: Benakis
authors.affiliation: 1] Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland [2] Department of Radiology, University of Geneva, Geneva, Switzerland [3] Department of Radiology, University of Lausanne, Lausanne, Switzerland [4] AIT, Center for Biomedical Imaging (CIBM), Institute of the Physics of Biological Systems, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Rolf
authors.initials: R
authors.lastname: Gruetter
authors.affiliation: Department of Clinical Neurosciences, Neurology Service, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Hirt
authors.affiliation: 1] Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland [2] Department of Radiology, University of Lausanne, Lausanne, Switzerland.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Lei
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D005973:Glutamine; D005680:gamma-Aminobutyric Acid