Increasing glucose load while maintaining normoglycemia does not evoke neuronal damage in prolonged critically ill rabbits.
OBJECTIVE
Preventing severe hyperglycemia with insulin reduced the neuropathological alterations in frontal cortex during critical illness. We investigated the impact of increasing glucose load under normoglycemia on neurons and glial cells.


METHODS
Hyperinflammatory critically ill rabbits were randomized to fasting or combined parenteral nutrition containing progressively increasing amounts of glucose (low, intermediate, high) within the physiological range but with a similar amount of amino acids and lipids. In all groups, normoglycemia was maintained with insulin. On day 7, we studied the neuropathological alterations in frontal cortex neurons, astrocytes and microglia, and MnSOD as marker of oxidative stress.


RESULTS
The percentage of damaged neurons was comparable among all critically ill and healthy rabbits. Critical illness induced an overall 1.8-fold increase in astrocyte density and activation status, largely irrespective of the nutritional intake. The percentage of microglia activation in critically ill rabbits was comparable with that in healthy rabbits, irrespective of glucose load. Likewise, MnSOD expression was comparable in critically ill and healthy rabbits without any clear impact of the nutritional interventions.


CONCLUSIONS
During prolonged critical illness, increasing intravenous glucose infusion while strictly maintaining normoglycemia appeared safe for neuronal integrity and did not substantially affect glial cells in frontal cortex.
Clinical Department, Laboratory of Intensive Care Medicine, Division of Cellular and Molecular Medicine, KU Leuven, B-3000 Leuven, Belgium; Department of Intensive Care Medicine, EA4342, Raymond Poincaré University Hospital, Garches, Université de Versailles-Saint Quentin, France; Histopathologie Humaine et Modèles Animaux, Département Infection et Epidémiologie, Institut Pasteur, Paris, France.
Romain
R
Sonneville
Heleen M
HM
den Hertog
Sarah
S
Derde
Fabian
F
Güiza
Inge
I
Derese
Greet
G
Van den Berghe
Ilse
I
Vanhorebeek
D061605:Administration, Intravenous; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016638:Critical Illness; D004195:Disease Models, Animal; D005947:Glucose / Q000008:administration & dosage*; D006943:Hyperglycemia / Q000097:blood / Q000517:prevention & control; D007328:Insulin / Q000097:blood; D008297:Male; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010288:Parenteral Nutrition; D011817:Rabbits
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose
Astrocyte; Critical illness; GAPDH; GFAP; GLUT-4; Glucose load; IV; Microglia; MnSOD; Neuron; Normoglycemia; glial fibrillary acidic protein; glucose transporter-4; glyceraldehyde-3-phosphate dehydrogenase; intravenous; manganese superoxide dismutase