Lipopolysaccharide, a component of the cell wall of Gram-negative bacteria, may be responsible for at least some of the pathophysiological sequelae of bacterial infections, probably by inducing an increase in interleukin-1 (IL-1) concentration. We report that intraperitoneal injection of lipopolysaccharide increased hippocampal caspase-1 activity and IL-1 concentration; these changes were associated with increased activity of the stress-activated kinase c-Jun NH 2 -terminal kinase, decreased glutamate release, and impaired long term potentiation. The degenerative changes in hippocampus and entorhinal cortical neurones were consistent with apoptosis because translocation of cytochrome c and poly(ADP-ribose) polymerase cleavage were increased. Inhibition of caspase-1 blocked these changes, suggesting that IL-1 mediated the lipopolysaccharide-induced changes.There is increasing awareness of the existence of bidirectional communication between the immune and nervous systems. The proinflammatory cytokine, interleukin-1 (IL-1), 1 is one molecule that may play a pivotal role in integrating neuronal immune responses with those of the endocrine system because it exerts significant effects in all systems, for example in response to stressors such as infection. Gram-negative bacterial infections are associated with multiple pathophysiological changes; it is widely accepted that these changes are stimulated by lipopolysaccharide (LPS), a component of the outer membrane of most Gram-negative bacteria. These changes, which include fever, changes in sleep pattern, and anorexia (1), are mimicked by, and therefore thought to be mediated through production of, IL-1. Thus LPS, injected centrally or peripherally, increases IL-1 concentrations (2, 3) and IL-1 mRNA expression (4) in rat brain.Although it appears that in certain circumstances IL-1 may be neuroprotective, the consensus is that prolonged exposure, or exposure of tissue to high concentrations of IL-1, results in degenerative changes (5). Therefore it is significant that increased IL-1 concentrations in different brain areas have been correlated with neurodegenerative disorders such as Down syndrome, Alzheimer's disease (6), and Parkinson's disease (7), whereas in experimental models, IL-1 is considered to be responsible for the cell damage associated with ischemia (8) and excitotoxicity (9) and is increased after experimental traumatic lesions (10). A striking example of a neuronal deficit induced by IL-1 is the impairment in long term potentiation (LTP) in the hippocampus in vitro (11-13) and in vivo (14 -16).IL-1 is produced by glia (17, 18) and neurones (19,20) in response to tissue stress. It is cleaved from the inactive percursor, pro-IL-1, by the action of caspase-1, a member of a large family of cysteine proteases that have been implicated in apoptotic cell death (21-25). It might be predicted therefore that any trigger such as LPS, which induces an increase in IL-1, will do so by increasing activity of caspase-1.Our objective was to investigate th...
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Mean glomerular volume has previously been estimated, using stereological techniques, specifically the pointsampled intercept (PSI), either from isotropic or from vertical sections. As glomeruli are approximately spherical structures, the same stereological technique was carried out on vertical and arbitrary sections to determine whether section orientation had any effect on mean glomerular volume estimation. Equine kidneys from 10 individuals were analysed using the PSI method of estimating volume-weighted mean glomerular volume (MGV) ; for each kidney, arbitrary and vertical sections were analysed. MGVs were not significantly different between arbitrary and vertical sections (P l 0n691) when analysing the data with the paired t test ; when plotting MGV estimates from arbitrary sections against those from vertical sections the intercept was found not to be significantly different from zero (P 0n8) and the slope of the regression line not to be significantly different from 1n0 (P 0n4). For the estimation of MGV in equine kidneys using PSI, arbitrary sections may be used if it is not possible to use isotropic or vertical sections, but some caution must be exercised in the interpretation of results so gained.
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