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- Title
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.
- Authors
Gullo, Francesca; Amadeo, Alida; Donvito, Giulia; Lecchi, Marzia; Costa, Barbara; Constanti, Andrew; Wanke, Enzo
- Abstract
We show here that a mild sterile inflammation induced by the endotoxin lipopolysaccharide (LPS), in a neuron/astrocyte/microglial cortical network, modulates neuronal excitability and can initiate long-duration burst events resembling epileptiform seizures, a recognized feature of various central nervous neurodegenerative, neurological and acute systemic diseases associated with neuroinflammation. To study this action, we simultaneously analyzed the reverberating bursting activity of a hundred neurons by using in vitro multielectrode array methods. ∼5 h after LPS application, we observed a net increase in the average number of spikes elicited in engaged cells and within each burst, but no changes neither in spike waveforms nor in burst rate.This effectwas characterized by a slow, twofold exponential increase of the burst duration and the appearance of rarely occurring long burst events that were never seen during control recordings.These changes and the time-course of microglia-released proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α), were blocked by pre-treatment with 50 nM minocycline, an established anti-inflammatory agent which was inactive when applied alone. Assay experiments also revealed that application of 60 pM exogenous TNF-α after 12-15 h, produced non-washable changes of neuronal excitability, completely different from those induced by LPS, suggesting thatTNF-α release alone was not responsible for our observed findings. Our results indicate that the link between neuroinflammation and hyperexcitability can be unveiled by studying the long-term activity of in vitro neuronal/astrocyte/microglial networks.
- Subjects
INFLAMMATION; PHYSIOLOGICAL effects of lipopolysaccharides; ENDOTOXINS; ENCEPHALITIS; TUMOR necrosis factors; ASTROCYTES
- Publication
Frontiers in Cellular Neuroscience, 2014, Vol 8, p1
- ISSN
1662-5102
- Publication type
Article
- DOI
10.3389/fncel.2014.00361