Impact of hyperglycemia on neuropathological alterations during critical illness.

Details

Serval ID
serval:BIB_0B3175E8CD1F
Type
Article: article from journal or magazin.
Collection
Publications
Title
Impact of hyperglycemia on neuropathological alterations during critical illness.
Journal
Journal of Clinical Endocrinology and Metabolism
Author(s)
Sonneville R., den Hertog H.M., Güiza F., Gunst J., Derese I., Wouters P.J., Brouland J.P., Polito A., Gray F., Chrétien F., Charlier P., Annane D., Sharshar T., Van den Berghe G., Vanhorebeek I.
ISSN
1945-7197 (Electronic)
ISSN-L
0021-972X
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
97
Number
6
Pages
2113-2123
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
CONTEXT: Although preventing excessive hyperglycemia during critical illness may provide clinical neuroprotection, it remains debated whether normoglycemia is without risk for the brain.
OBJECTIVE: To address this question, we compared the neuropathological alterations in microglia, astrocytes, and neurons, with uncontrolled hyperglycemia, moderately controlled hyperglycemia, and normoglycemia during human critical illness. We further investigated the time course in an animal model.
DESIGN AND SETTING: We analyzed brain specimens from patients who died in the intensive care unit and from critically ill rabbits randomized to hyper- or normoglycemia. PATIENTS/OTHER PARTICIPANTS: We compared 10 critically ill patients randomized to normoglycemia (104 ±9 mg/dl) or moderate hyperglycemia (173 ±32 mg/dl), and five patients with uncontrolled hyperglycemia (254 ±83 mg/dl) with 16 controls (out of hospital sudden deaths). Critically ill rabbits were randomized to hyperglycemia (315 ±32 mg/dl) or normoglycemia (85 ±13 mg/dl) and studied after 3 and 7 d.
INTERVENTIONS: Insulin was infused to control blood glucose.
MAIN OUTCOME MEASURES AND RESULTS: Patients with uncontrolled hyperglycemia showed 3.7-6-fold increased microglial activation, 54-95% reduced number and activation of astrocytes, more than 9-fold increased neuronal and glial apoptosis, and a 1.5-2-fold increase in damaged neurons in hippocampus and frontal cortex (all P ≤ 0.05). Most of these abnormalities were attenuated with moderate hyperglycemia and virtually absent with normoglycemia. Frontal cortex of hyperglycemic rabbits that had been critically ill for 3 d only revealed microglial activation, followed after 7 d by astrocyte and neuronal abnormalities similar to those observed in patients, all prevented by normoglycemia.
CONCLUSIONS: Preventing hyperglycemia with insulin during critical illness reduced neuropathological abnormalities, with microglial activation being the earliest preventable event. Whether these pathological findings associate with neurological outcome remains unknown.
Keywords
Adult, Aged, Animals, Blood Glucose/metabolism, Brain Diseases/mortality, Brain Diseases/pathology, Critical Illness/mortality, Disease Models, Animal, Female, Frontal Lobe/pathology, Hippocampus/pathology, Humans, Hyperglycemia/drug therapy, Hyperglycemia/mortality, Hypoglycemic Agents/therapeutic use, Insulin/therapeutic use, Male, Microglia/metabolism, Microglia/pathology, Middle Aged, Rabbits, Risk Factors
Pubmed
Web of science
Open Access
Yes
Create date
13/10/2015 10:15
Last modification date
20/08/2019 12:32
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