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Preischemic hyperglycemia and postischemic alteration of rat brain pyruvate dehydrogenase activity

Lundgren, J. LU ; Cardell, M. LU ; Wieloch, T. LU and Siesjo, B. K. LU (1990) In Journal of Cerebral Blood Flow and Metabolism 10(4). p.536-541
Abstract

Transient cerebral ischemia in normoglycemic animals is followed by a decrease in glucose utilization, reflecting a postischemic cerebral metabolic depression and a reduction in the activity of the pyruvate dehydrogenase complex (PDHC). Preischemic hyperglycemia, which aggravates ischemic brain damage and invariably causes seizure, is known to further reduce cerebral metabolic rate. To investigate whether these effects are accompanied by changes in PDHC activity, the postischemic cerebral cortical activity of this enzyme was investigated in rats with preischemic hyperglycemia (plasma glucose 20-25 mM). The results were compared with those obtained in normoglycemic animals (plasma glucose 5-10 mM). The activated portion of PDHC and total... (More)

Transient cerebral ischemia in normoglycemic animals is followed by a decrease in glucose utilization, reflecting a postischemic cerebral metabolic depression and a reduction in the activity of the pyruvate dehydrogenase complex (PDHC). Preischemic hyperglycemia, which aggravates ischemic brain damage and invariably causes seizure, is known to further reduce cerebral metabolic rate. To investigate whether these effects are accompanied by changes in PDHC activity, the postischemic cerebral cortical activity of this enzyme was investigated in rats with preischemic hyperglycemia (plasma glucose 20-25 mM). The results were compared with those obtained in normoglycemic animals (plasma glucose 5-10 mM). The activated portion of PDHC and total PDHC activity were measured in neocortical samples as the rate of decarboxylation of [14C]pyruvate in crude brain mitochondrial homogenates after 5 min, 15 min, 1 h, 6 h, and 18 h of recirculation following 15 min of incomplete cerebral ischemia. In normoglycemic animals the fraction of activated PDHC, which rises abruptly during ischemia, was reduced to 19-25% during recirculation compared with 30% in sham-operated controls. In hyperglycemic rats the fraction of activated PDHC was higher during the first 15 min of recirculation. However, after 1 and 6 h of recirculation, the fraction was reduced to values similar to those measured in normoglycemic animals. Fifteen of 26 rats experienced early (1-4 h post ischemia) seizures in the recovery period. The PDHC activity appeared unchanged prior to these early postischemic seizures. We conclude that the accentuated depression of postischemic metabolic rate observed in hyperglycemic animals is not coupled to a corresponding postischemic depression of PDHC. The relative increase in the fraction of activated PDHC in the early recovery phase in hyperglycemic animals probably reflects either increased intramitochondrial calcium levels or persistent increases in the NADH/NAD and/or ADP/ATP ratios.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Brain, Complex, Hyperglycemia, Ischemia, Pyruvate dehydrogenase
in
Journal of Cerebral Blood Flow and Metabolism
volume
10
issue
4
pages
6 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:0025351471
  • pmid:2347883
ISSN
0271-678X
DOI
10.1038/jcbfm.1990.95
language
English
LU publication?
yes
id
adc0e6bb-4cf5-4682-94ac-77c1fe0f33da
date added to LUP
2019-06-13 16:36:41
date last changed
2019-11-25 09:31:31
@article{adc0e6bb-4cf5-4682-94ac-77c1fe0f33da,
  abstract     = {<p>Transient cerebral ischemia in normoglycemic animals is followed by a decrease in glucose utilization, reflecting a postischemic cerebral metabolic depression and a reduction in the activity of the pyruvate dehydrogenase complex (PDHC). Preischemic hyperglycemia, which aggravates ischemic brain damage and invariably causes seizure, is known to further reduce cerebral metabolic rate. To investigate whether these effects are accompanied by changes in PDHC activity, the postischemic cerebral cortical activity of this enzyme was investigated in rats with preischemic hyperglycemia (plasma glucose 20-25 mM). The results were compared with those obtained in normoglycemic animals (plasma glucose 5-10 mM). The activated portion of PDHC and total PDHC activity were measured in neocortical samples as the rate of decarboxylation of [<sup>14</sup>C]pyruvate in crude brain mitochondrial homogenates after 5 min, 15 min, 1 h, 6 h, and 18 h of recirculation following 15 min of incomplete cerebral ischemia. In normoglycemic animals the fraction of activated PDHC, which rises abruptly during ischemia, was reduced to 19-25% during recirculation compared with 30% in sham-operated controls. In hyperglycemic rats the fraction of activated PDHC was higher during the first 15 min of recirculation. However, after 1 and 6 h of recirculation, the fraction was reduced to values similar to those measured in normoglycemic animals. Fifteen of 26 rats experienced early (1-4 h post ischemia) seizures in the recovery period. The PDHC activity appeared unchanged prior to these early postischemic seizures. We conclude that the accentuated depression of postischemic metabolic rate observed in hyperglycemic animals is not coupled to a corresponding postischemic depression of PDHC. The relative increase in the fraction of activated PDHC in the early recovery phase in hyperglycemic animals probably reflects either increased intramitochondrial calcium levels or persistent increases in the NADH/NAD and/or ADP/ATP ratios.</p>},
  author       = {Lundgren, J. and Cardell, M. and Wieloch, T. and Siesjo, B. K.},
  issn         = {0271-678X},
  language     = {eng},
  month        = {07},
  number       = {4},
  pages        = {536--541},
  publisher    = {Nature Publishing Group},
  series       = {Journal of Cerebral Blood Flow and Metabolism},
  title        = {Preischemic hyperglycemia and postischemic alteration of rat brain pyruvate dehydrogenase activity},
  url          = {http://dx.doi.org/10.1038/jcbfm.1990.95},
  doi          = {10.1038/jcbfm.1990.95},
  volume       = {10},
  year         = {1990},
}