Lipopolysaccharides do not alter metabolic disturbances in hippocampal slices of fetal guinea pigs after oxygen-glucose deprivation

The aim of the present study was to clarify whether endotoxins [lipopolysac charides (LPS)] have a toxic effect on fetal brain tissue after cerebral is chemia, while excluding their effect on the cardiovascular system. Experime nts were therefore performed on hippocampal slices prepared from mature fet al guinea pigs. In particular, we studied the influence of LPS on nitric ox ide production, energy metabolism, and protein synthesis after oxygen-gluco se deprivation (OGD). Incubating hippocampal slices in LPS (4 mg/L) for as long as 12 h did not alter cGMP tissue concentrations significantly. Howeve r, 10 min after OGD of 40-min duration, cGMP tissue concentrations were sub stantially increased in relation to controls, and this increase was almost completely blocked by the application of 100 mu M N-omega-nitro-L-arginine, indicating that nitric oxide synthase was activated after OGD in fetal bra in tissue. Again, LPS did not have any effect on cGMP tissue concentrations after OGD. Furthermore, addition of LPS altered neither protein synthesis nor energy metabolism measured 12 h after OGD. We therefore conclude that, apart from their well-known influence on the cardiovascular system, LPS do not alter metabolic disturbances in hippocampal slices of fetal guinea pigs 12 h after OGD. A direct toxic effect of LPS on immature brain tissue with in this interval does not therefore seem to be very likely. However, delaye d activation of LPS-sensitive pathways that may be involved in cell death, or damage limited to a small subgroup of cells such as oligodendrocyte prog enitors, cannot be fully excluded.