Acute lipopolysaccharide exposure facilitates epileptiform activity via enhanced excitatory synaptic transmission and neuronal excitability in vitro

Abstract

Growing evidence indicates brain inflammation has been involved in the genesis of seizures. However, the direct effect of acute inflammation on neuronal circuits is not well known. Lipopolysaccharide (LPS) has been used extensively to stimulate brain inflammatory responses both in vivo and in vitro. Here, we observed the contribution of inflammation induced by 10 μg/mL LPS to the excitability of neuronal circuits in acute hippocampal slices. When slices were incubated with LPS for 30 minutes, significant increased concentration of tumor necrosis factor α and interleukin 1β were detected by enzyme-linked immunosorbent assay. In electrophysiological recordings, we found that frequency of epileptiform discharges and spikes per burst increased 30 minutes after LPS application. LPS enhanced evoked excitatory postsynaptic currents but did not modify evoked inhibitory postsynaptic currents. In addition, exposure to LPS enhanced the excitability of CA1 pyramidal neurons, as demonstrated by a decrease in rheobase and an increase in action potential frequency elicited by depolarizing current injection. Our observations suggest that acute inflammation induced by LPS facilitates epileptiform activity in vitro and that enhancement of excitatory synaptic transmission and neuronal excitability may contribute to this facilitation. These results may provide new clues for treating seizures associated with brain inflammatory disease.

Impact of the Innate Immune Response in the Actions of Ethanol on the Central Nervous System

“…IL‐1 β and IL‐6 are also involved in the modulation and maintenance of long‐term potentiation (LTP) in vivo (del Rey et al., ). Recent studies have suggested that TLR4/HMGB1 signaling may impact neuronal excitability by interacting with NMDA receptors (Balosso et al., ; Maroso et al., ), and LPS facilitates epileptiform activity in vitro by enhancing excitatory synaptic transmission and neuronal excitability (Gao et al., ). EtOH‐induced HMGB1 release is also associated with NOX2/NLRP1 inflammasome signaling, which represents a new mechanism of EtOH‐associated neuron injury (Wang et al., ).…”

KV7/M channels as targets for lipopolysaccharide‐induced inflammatory neuronal hyperexcitability

“…; Gao et al . ). At the cellular level, acute application of LPS to hippocampal slices was reported to enhance the frequency of excitatory postsynaptic currents (EPSCs; Pascual et al .…”

“…) and to increase neuronal excitability (Gao et al . ). These two actions, cooperatively, may underlie LPS‐induced brain hyperexcitability.…”

“…Thus, when applied on the cortex of sedated rats, LPS induces epileptiform discharges within minutes, sometimes culminating in full-blown seizures (Rodgers et al 2009). Likewise, when applied acutely to hippocampal slices, LPS facilitates the generation of epileptiform discharges (Pascual et al 2012;Gao et al 2014). At the cellular level, acute application of LPS to hippocampal slices was reported to enhance the frequency of excitatory postsynaptic currents (EPSCs; Pascual et al 2012) and to increase neuronal excitability (Gao et al 2014).…”

“…Likewise, when applied acutely to hippocampal slices, LPS facilitates the generation of epileptiform discharges (Pascual et al 2012;Gao et al 2014). At the cellular level, acute application of LPS to hippocampal slices was reported to enhance the frequency of excitatory postsynaptic currents (EPSCs; Pascual et al 2012) and to increase neuronal excitability (Gao et al 2014). These two actions, cooperatively, may underlie LPS-induced brain hyperexcitability.…”