Evolution of the neurochemical profile after transient focal cerebral ischemia in the mouse brain.
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.
Lei
Hongxia
H
Laboratory of Functional and Metabolic Imaging, Institute of the Physics of Biological System, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. hongxia.lei@epfl.ch
Berthet
Carole
C
Hirt
Lorenz
L
Gruetter
Rolf
R
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
D005973:Glutamine; D001224:Aspartic Acid; D019344:Lactic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D005947:Glucose