A rat four vessel occlusion model was utilized to examine the effects of
ischemia/reperfusion on cortical window superfusate levels of
amino acids,
glucose, and
lactate. Superfusate
aspartate,
glutamate,
phosphoethanolamine,
taurine, and
GABA were significantly elevated by
cerebral ischemia, then declined during reperfusion. Other
amino acids were affected to a lesser degree. Superfusate
lactate rose slightly during the initial ischemic period, declined during continued
cerebral ischemia and then was greatly elevated during reperfusion. Superfusate
glucose levels declined to near zero levels during
ischemia and then rebounded beyond basal levels during the reperfusion period. Inhibition of neuronal
lactate uptake with
alpha-cyano-4-hydroxycinnamate dramatically elevated superfusate
lactate levels, enhanced the
ischemia/reperfusion evoked release of
aspartate but reduced
glutamine levels. Topical application of an alternative metabolic fuel,
glutamine, had a dose dependent effect.
Glutamine (1 mM) elevated basal superfusate
glucose levels, diminished the decline in
glucose during
ischemia, and accelerated its recovery during reperfusion.
Lactate levels were elevated during
ischemia and reperfusion. These effects were not evident at 5 mM
glutamine. At both concentrations,
glutamine significantly elevated the superfusate levels of
glutamate. Topical application of
sodium pyruvate (20 mM) significantly attenuated the decline in superfusate
glucose during
ischemia and enhanced the levels of both
glucose and
lactate during reperfusion. However, it had little effect on the
ischemia-evoked accumulation of
amino acids. Topical application of
glucose (450 mg/dL) significantly elevated basal superfusate levels of
lactate, which continued to be elevated during both
ischemia and reperfusion. The
ischemia-evoked accumulations of
aspartate,
glutamate,
taurine and
GABA were all significantly depressed by
glucose, while
phosphoethanolamine levels were elevated. These results support the role of
lactate in neuronal metabolism during
ischemia/reperfusion. Both
glucose and
glutamine were also used as energy substrates. In contrast,
sodium pyruvate does not appear to be as effectively utilized by the ischemic/reperfused rat brain since it did not reduce
ischemia-evoked
amino acid efflux.