From the Servicio de Neurocirugía, Hospital La Paz (J.M.P., F.C.,
J.M.R.), and Instituto de Investigaciones Biomédicas del C.S.I.C.
(S.C.), Madrid, Spain.
Correspondence to Dr Sebastian Cerdán, Instituto de Investigaciones Biomédicas del C.S.I.C., c/Arturo Duperier 4, E-28029 Madrid, Spain. E-mail scerdan{at}biomed.iib.uam.es
Background and PurposeEven though
the utilization of substrates alternative to glucose may play an
important role in the survival of brain cells under ischemic
conditions, evidence on changes in substrate selection by the adult
brain in vivo during ischemic episodes remains very limited.
This study investigates the utilization of glutamate, glutamine, and
GABA as fuel by the neuronal and glial tricarboxylic acid cycles of
both cerebral hemispheres after partially reversible focal cerebral
ischemia (FCI).
MethodsRight hemisphere infarct was induced in adult Long-Evans
rats by permanent occlusion of the right middle cerebral artery and
transitory occlusion of both common carotid arteries.
(1,2-13C2) acetate was infused for 60 minutes
in the right carotid artery immediately after carotid recirculation had
been re-established (1-hour group) or 23 hours later (24-hour group).
Extracts from both cerebral hemispheres were prepared and
analyzed separately by 13C nuclear magnetic
resonance and computer-assisted metabolic modeling.
ResultsFCI decreased the oxidative metabolism of
glucose in the brain in a time-dependent manner. Reduced glucose
oxidation was compensated for by increased oxidations of
(13C) glutamate and (13C) GABA in the
astrocytes of the ipsilateral hemispheres of both groups. Increased
oxidative metabolism of (13C) glutamine in the
neurons was favored by increased activity of the neuronal pyruvate
recycling system in the 24hour group.
ConclusionsData were obtained consistent with
time-dependent changes in the utilization of glutamate and GABA or
glutamine as metabolic substrates for the glial or neuronal
compartments of rat brain after FCI.
Anesthesiology/Critical
Care Medicine The Johns Hopkins
University Baltimore, Maryland
© 1998 American Heart Association, Inc.
Original Contributions
Glutamate, Glutamine, and GABA as Substrates for the Neuronal and Glial Compartments After Focal Cerebral Ischemia in Rats
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