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Cerebral glutamine and glutamate levels in relation to compromised energy metabolism : a microdialysis study in subarachnoid hemorrhage patients

Samuelsson, Carolina LU ; Hillered, Lars ; Zetterling, Maria ; Enblad, Per ; Hesselager, Göran ; Ryttlefors, Mats ; Kumlien, Eva ; Lewén, Anders ; Marklund, Niklas LU and Nilsson, Pelle , et al. (2007) In Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 27(7). p.17-1309
Abstract

Astrocytic glutamate (Glt) uptake keeps brain interstitial Glt levels low. Within the astrocytes Glt is converted to glutamine (Gln), which is released and reconverted to Glt in neurons. The Glt-Gln cycle is energy demanding and impaired energy metabolism has been suggested to cause low interstitial Gln/Glt ratios. Using microdialysis (MD) measurements from visually noninjured cortex in 33 neurointensive care patients with subarachnoid hemorrhage, we have determined how interstitial Glt and Gln, as a reflection of the Glt-Gln cycle turnover, relate to perturbed energy metabolism. A total of 3703 hourly samples were analyzed. The lactate/pyruvate (L/P) ratios correlated to the Gln/Glt ratios (r=-0.66), but this correlation was not... (More)

Astrocytic glutamate (Glt) uptake keeps brain interstitial Glt levels low. Within the astrocytes Glt is converted to glutamine (Gln), which is released and reconverted to Glt in neurons. The Glt-Gln cycle is energy demanding and impaired energy metabolism has been suggested to cause low interstitial Gln/Glt ratios. Using microdialysis (MD) measurements from visually noninjured cortex in 33 neurointensive care patients with subarachnoid hemorrhage, we have determined how interstitial Glt and Gln, as a reflection of the Glt-Gln cycle turnover, relate to perturbed energy metabolism. A total of 3703 hourly samples were analyzed. The lactate/pyruvate (L/P) ratios correlated to the Gln/Glt ratios (r=-0.66), but this correlation was not stronger than the correlation between L/P and Glt (r=0.68) or the correlation between lactate and Glt (r=0.65). A novel observation was a linear relationship between interstitial pyruvate and Gln (r=0.52). There were 13 periods (404 h) of 'energy crisis', defined by L/P ratios above 40. All were associated with high interstitial Glt levels. Periods with L/P ratios above 40 and low pyruvate levels were associated with decreased interstitial Gln levels, suggesting ischemia and failing astrocytic Gln synthesis. Periods with L/P ratios above 40 and normal or high pyruvate levels were associated with increased interstitial Gln levels, which may represent an astrocytic hyperglycolytic response to high interstitial Glt levels. The results imply that moderately elevated L/P ratios cannot always be interpreted as failing energy metabolism and that interstitial pyruvate levels may discriminate whether or not there is sufficient astrocytic capacity for Glt-Gln cycling in the brain.

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publishing date
type
Contribution to journal
publication status
published
keywords
Astrocytes, Brain, Energy Metabolism, Female, Glutamic Acid, Glutamine, Humans, Lactic Acid, Male, Microdialysis, Neurons, Pyruvic Acid, Subarachnoid Hemorrhage, Journal Article
in
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
volume
27
issue
7
pages
17 - 1309
publisher
Nature Publishing Group
external identifiers
  • pmid:17228333
  • scopus:34250857435
ISSN
0271-678X
DOI
10.1038/sj.jcbfm.9600433
language
English
LU publication?
no
id
f7978c73-b1eb-47c9-b056-3d51e52e56c8
date added to LUP
2018-03-03 14:35:34
date last changed
2021-01-06 06:28:59
@article{f7978c73-b1eb-47c9-b056-3d51e52e56c8,
  abstract     = {<p>Astrocytic glutamate (Glt) uptake keeps brain interstitial Glt levels low. Within the astrocytes Glt is converted to glutamine (Gln), which is released and reconverted to Glt in neurons. The Glt-Gln cycle is energy demanding and impaired energy metabolism has been suggested to cause low interstitial Gln/Glt ratios. Using microdialysis (MD) measurements from visually noninjured cortex in 33 neurointensive care patients with subarachnoid hemorrhage, we have determined how interstitial Glt and Gln, as a reflection of the Glt-Gln cycle turnover, relate to perturbed energy metabolism. A total of 3703 hourly samples were analyzed. The lactate/pyruvate (L/P) ratios correlated to the Gln/Glt ratios (r=-0.66), but this correlation was not stronger than the correlation between L/P and Glt (r=0.68) or the correlation between lactate and Glt (r=0.65). A novel observation was a linear relationship between interstitial pyruvate and Gln (r=0.52). There were 13 periods (404 h) of 'energy crisis', defined by L/P ratios above 40. All were associated with high interstitial Glt levels. Periods with L/P ratios above 40 and low pyruvate levels were associated with decreased interstitial Gln levels, suggesting ischemia and failing astrocytic Gln synthesis. Periods with L/P ratios above 40 and normal or high pyruvate levels were associated with increased interstitial Gln levels, which may represent an astrocytic hyperglycolytic response to high interstitial Glt levels. The results imply that moderately elevated L/P ratios cannot always be interpreted as failing energy metabolism and that interstitial pyruvate levels may discriminate whether or not there is sufficient astrocytic capacity for Glt-Gln cycling in the brain.</p>},
  author       = {Samuelsson, Carolina and Hillered, Lars and Zetterling, Maria and Enblad, Per and Hesselager, Göran and Ryttlefors, Mats and Kumlien, Eva and Lewén, Anders and Marklund, Niklas and Nilsson, Pelle and Salci, Konstantin and Ronne-Engström, Elisabeth},
  issn         = {0271-678X},
  language     = {eng},
  number       = {7},
  pages        = {17--1309},
  publisher    = {Nature Publishing Group},
  series       = {Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism},
  title        = {Cerebral glutamine and glutamate levels in relation to compromised energy metabolism : a microdialysis study in subarachnoid hemorrhage patients},
  url          = {http://dx.doi.org/10.1038/sj.jcbfm.9600433},
  doi          = {10.1038/sj.jcbfm.9600433},
  volume       = {27},
  year         = {2007},
}