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Hyperglycaemia and apoptosis of microglial cells in human septic shock

Andrea Polito1, Jean-Philippe Brouland2, Raphael Porcher3, Romain Sonneville16, Shidasp Siami1, Robert D Stevens4, Céline Guidoux1, Virginie Maxime1, Geoffroy Lorin de la Grandmaison5, Fabrice C Chrétien6, Françoise Gray2, Djillali Annane1 and Tarek Sharshar1*

Author Affiliations

1 General Intensive Care Medicine, Raymond Poincaré Hospital (AP-HP), University of Versailles Saint Quentin en Yvelines, 104 bd R. Poincaré, Garches 92210, France

2 Department of Pathology, Lariboisière Hospital (AP-HP), University Denis Diderot-Paris 7, 2 rue Ambroise Paré, Paris 75010, France

3 Departement of Biostatistic and Medical Informatics, Saint-Louis Hospital (APHP), University Denis Diderot-Paris 7, 47-83, boulevard de l'Hôpital, Paris 75010, France

4 Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA

5 Department of Pathology, Raymond Poincaré Hospital (AP-HP), University of Versailles Saint Quentin en Yvelines, 104 bd R. Poincaré, Garches 92210, France

6 HISTO, Human Histopathology and Animal Models; Institut Pasteur; Département Infection et Epidémiologie, 25 rue du Dr Roux, 75015 Paris

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Critical Care 2011, 15:R131  doi:10.1186/cc10244

Published: 25 May 2011



The effect of hyperglycaemia on the brain cells of septic shock patients is unknown. The objective of this study was to evaluate the relationship between hyperglycaemia and apoptosis in the brains of septic shock patients.


In a prospective study of 17 patients who died from septic shock, hippocampal tissue was assessed for neuronal ischaemia, neuronal and microglial apoptosis, neuronal Glucose Transporter (GLUT) 4, endothelial inducible Nitric Oxide Synthase (iNOS), microglial GLUT5 expression, microglial and astrocyte activation. Blood glucose (BG) was recorded five times a day from ICU admission to death. Hyperglycaemia was defined as a BG 200 mg/dL g/l and the area under the BG curve (AUBGC) > 2 g/l was assessed.


Median BG over ICU stay was 2.2 g/l. Neuronal apoptosis was correlated with endothelial iNOS expression (rho = 0.68, P = 0.04), while microglial apoptosis was associated with AUBGC > 2 g/l (rho = 0.70; P = 0.002). Neuronal and microglial apoptosis correlated with each other (rho = 0.69, P = 0.006), but neither correlated with the duration of septic shock, nor with GLUT4 and 5 expression. Neuronal apoptosis and ischaemia tended to correlate with duration of hypotension.


In patients with septic shock, neuronal apoptosis is rather associated with iNOS expression and microglial apoptosis with hyperglycaemia, possibly because GLUT5 is not downregulated. These data provide a mechanistic basis for understanding the neuroprotective effects of glycemic control.