Case 7359, Cerebral sellectchem 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 …Figure 2Axonal 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 …Figure 3Hippocampal expression of GLUT4. Hippocampal interneurons in CA1 and CA4 exhibit a homogeneous cytoplasmic staining (arrow) with GLUT4 antibody (ABC/peroxidase/DAB, x40).Figure 4Hippocampal 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).

Table 3Association of neuronal GLUT4 and microglial GLUT5 expression with glycaemia and cell apoptosisDiscussionIn patients dying of septic shock, hyperglycaemia was associated with microglial apoptosis while neuronal apoptosis was preferentially associated with endothelial iNOS expression. We also found that hyperglycaemia tended to be correlated with CD68 expression, which is a marker of microglial activation. The postulated relationship between hyperglycaemia and microglial cell apoptosis was supported by its absence of statistical correlation with hypotension, hypoxemia or hypernatremia, while it is known that hippocampus is highly vulnerable to these factors.

We also found that neuronal GLUT4 and microglial GLUT5 expressions were not correlated with blood glucose level, suggesting impaired downregulation.These results are consistent with several experimental studies. Discrepancy between microglial CD68 and HLA-DR immunostaining has been previously observed [25] and was ascribed to the fact that CD68 is a better marker of activated microglia. Nitric oxide has been extensively documented as pro-apoptotic factor, notably in experimental sepsis [26-28]. In experimental models of cerebral trauma or ischaemia, hyperglycaemia has been linked to neuronal and glial cell injury through various mechanisms including mitochondrial dysfunction, oxidative stress, inflammation and excitotoxicity [29]. Although the similar mechanisms have been implicated in sepsis associated encephalopathy, the potential contribution of hyperglycaemia had not been elucidated.

It was recently shown that high glucose and LPS synergistically induce microglial apoptosis by enhancing formation of oxidative Drug_discovery free radicals [13]. Interestingly, the statistical correlation between neuronal and microglial apoptosis suggest that they are interdependent phenomenon. It is established that neuronal function and survival is intimately linked to both astroglial and microglial cells [30].