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. 2011;15(3):R131.
doi: 10.1186/cc10244. Epub 2011 May 25.

Hyperglycaemia and apoptosis of microglial cells in human septic shock

Andrea Polito  1 , Jean-Philippe Brouland, Raphael Porcher, Romain Sonneville, Shidasp Siami, Robert D Stevens, Céline Guidoux, Virginie Maxime, Geoffroy Lorin de la Grandmaison, Fabrice C Chrétien, Françoise Gray, Djillali Annane, Tarek Sharshar
Affiliations

Hyperglycaemia and apoptosis of microglial cells in human septic shock

Andrea Polito et al. Crit Care. 2011.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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Figures

Figure 1
Figure 1
Neuronal and microglial apoptosis in cerebral amygdale. Case 7359, Cerebral amygdala. The back arrows show two apoptotic neurons with darkly stained nucleus. The red arrow shows an apoptotic microglial cell with a dark nucleus. The cytoplasm of the apoptotic cells is also stained corresponding to disintegration of nuclear chromatin into apoptotic bodies. (ISEL ×800).
Figure 2
Figure 2
Axonal damage in the hippocampal white matter. Cortico-subcortical junction in the hippocampus. Black arrows show axonal swellings in the white matter. These represent the accumulation of the precursor of the beta-amyloid protein due to alteration of the axonal flow. (APP imunostaining ABC/peroxidase/DAB x25).
Figure 3
Figure 3
Hippocampal expression of GLUT4. Hippocampal interneurons in CA1 and CA4 exhibit a homogeneous cytoplasmic staining (arrow) with GLUT4 antibody (ABC/peroxidase/DAB, x40).
Figure 4
Figure 4
Hippocampal expression of GLUT5. In hippocampal interneurons (CA1 and CA4), microglial cells are strongly stained (arrows) whereas neurons are not labelled with GLUT5 antibody (ABC/peroxidase/DAB, x25).
See this image and copyright information in PMC

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