LPS-Induced Microglial Secretion of TNFα Increases Activity-Dependent Neuronal Apoptosis in the Neonatal Cerebral Cortex

Abstract

During the pre-and neonatal period, the cerebral cortex reveals distinct patterns of spontaneous synchronized activity, which is critically involved in the formation of early networks and in the regulation of neuronal survival and programmed cell death (apoptosis). During this period, the cortex is also highly vulnerable to inflammation and in humans prenatal infection may have a profound impact on neurodevelopment causing long-term neurological deficits. Using in vitro and in vivo multi-electrode array recordings and quantification of caspase-3 (casp-3)-dependent apoptosis, we demonstrate that lipopolysaccharide-induced inflammation causes rapid alterations in the pattern of spontaneous burst activities, which subsequently leads to an increase in apoptosis. We show that these inflammatory effects are specifically initiated by the microglia-derived pro-inflammatory cytokine tumor necrosis factor a and the chemokine macrophage inflammatory protein 2. Our data demonstrate that inflammation-induced modifications in spontaneous network activities influence casp-3-dependent cell death in the developing cerebral cortex.

Multifaceted effects of oligodendroglial exosomes on neurons: impact on neuronal firing rate, signal transduction and gene regulation

“…The relative burst index is a measurement for the synchronicity of the neuronal network activity. A lower burst index indicates that neurons fire in a less synchronized fashion [23,24]. In summary, administration of oligodendroglial exosomes resulted in an increased number of action potentials with unaltered spike amplitude.…”

Atypical “seizure-like” activity in cortical reverberating networks in vitro can be caused by LPS-induced inflammation: a multi-electrode array study from a hundred neurons

“…Lipopolysaccharide was not used at higher concentrations because it has been recently shown that at 10 μg/ml, other remarkable effects lead to apoptosis (Nimmervoll et al, 2012). Another 10 experiments performed at lower LPS concentrations of 1 μg/ml produced data that were either transient (3 out of 10) or subject to the intrinsic variability among different dishes (3 out of 10) and therefore were not sufficiently stable and trustable to be analyzed further.…”

Hypothermia Does Not Reverse Cellular Responses Caused by Lipopolysaccharide in Neonatal Hypoxic-Ischaemic Brain Injury

“…Nimmervoll et al [34] have shown that LPS-induced microglial secretion of TNFα increases activity-dependent neuronal apoptosis in the neonatal cerebral cortex. Microglia may play a critical role in our model as well.…”