title: Evolution of the neurochemical profile after transient focal cerebral ischemia in the mouse brain.
abstract: Evolution of the neurochemical profile consisting of 19 metabolites after 30 mins of middle cerebral artery occlusion was longitudinally assessed at 3, 8 and 24 h in 6 to 8 microL volumes in the striatum using localized 1H-magnetic resonance spectroscopy at 14.1 T. Profound changes were detected as early as 3 h after ischemia, which include elevated lactate levels in the presence of significant glucose concentrations, decreases in glutamate and a transient twofold glutamine increase, likely to be linked to the excitotoxic release of glutamate and conversion into glial glutamine. Interestingly, decreases in N-acetyl-aspartate (NAA), as well as in taurine, exceeded those in neuronal glutamate, suggesting that the putative neuronal marker NAA is rather a sensitive marker of neuronal viability. With further ischemia evolution, additional, more profound concentration decreases were detected, reflecting a disruption of cellular functions. We conclude that early changes in markers of energy metabolism, glutamate excitotoxicity and neuronal viability can be detected with high precision non-invasively in mice after stroke. Such investigations should lead to a better understanding and insight into the sequential early changes in the brain parenchyma after ischemia, which could be used for identifying new targets for neuroprotection.
authors.affiliation: Laboratory of Functional and Metabolic Imaging, Institute of the Physics of Biological System, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. hongxia.lei@epfl.ch
authors.forename: Hongxia
authors.initials: H
authors.lastname: Lei
authors.forename: Carole
authors.initials: C
authors.lastname: Berthet
authors.forename: Lorenz
authors.initials: L
authors.lastname: Hirt
authors.forename: Rolf
authors.initials: R
authors.lastname: Gruetter
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D002560:Cerebrovascular Circulation; D003342:Corpus Striatum / Q000378:metabolism; D005947:Glucose / Q000032:analysis; D018698:Glutamic Acid / Q000032:analysis; D005973:Glutamine / Q000032:analysis; D020244:Infarction, Middle Cerebral Artery; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D007700:Kinetics; D019344:Lactic Acid / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy; D008660:Metabolism; D051379:Mice
chemical_list: D005973:Glutamine; D001224:Aspartic Acid; D019344:Lactic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D005947:Glucose