Abstract:
:To provide insights into the effects of temporary focal ischemia on the function of neurons and astrocytes in vivo, we measured the incorporation of radiolabel from [U-14C]glucose into both glutamate and glutamine in brain subregions at 1 h of reperfusion following occlusion of the middle cerebral artery for 2 or 3 h. Under the experimental conditions used, 14C-glutamate is mainly produced in neurons whereas 14C-glutamine is generated in astrocytes from 14C-glutamate of both neuronal and astrocytic origin. Radiolabel incorporation into both amino acids was greatly decreased. The change in 14C-glutamate accumulation provides strong evidence for substantial reductions in neuronal glucose metabolism. The resulting decrease in delivery of 14C-glutamate from the neurons to astrocytes was probably also the major contributor to the change in 14C-glutamine content. These alterations probably result in part from a marked depression of glycolytic activity in the neurons, as suggested by previous studies assessing deoxyglucose utilization. Alterations in 14C-glucose metabolism were not restricted to tissue that would subsequently become infarcted. Thus, these changes did not inevitably lead to death of the affected cells. The ATP : ADP ratio and phosphocreatine content were essentially preserved during recirculation following 2 h of ischemia and showed at most only moderate losses in some subregions following 3 h of ischemia. This retention of energy reserves despite the decreases in 14C-glucose metabolism in neurons suggests that energy needs were substantially reduced in the post-ischemic brain. Marked increases in tissue lactate accumulation during recirculation, particularly following 3 h of ischemia, provided evidence that impaired pyruvate oxidation probably also contributed to the altered 14C-glucose metabolism. These findings indicate the presence of complex changes in energy metabolism that are likely to greatly influence the responses of neurons and astrocytes to temporary focal ischemia.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Thoren AE,Helps SC,Nilsson M,Sims NRdoi
10.1111/j.1471-4159.2006.03778.xsubject
Has Abstractpub_date
2006-05-01 00:00:00pages
968-78issue
4eissn
0022-3042issn
1471-4159pii
JNC3778journal_volume
97pub_type
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journal_title:Journal of neurochemistry
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更新日期:1997-12-01 00:00:00
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