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

Figures & data

Figure 1 Exposure to 10 μg/mL lipopolysaccharide (LPS) for 30 minutes elevated interleukin (IL)-1β (A) and tumor necrosis factor (TNF)-α (B) concentration in brain slices.

Note: **Significant difference (P<0.01; n=5; independent samples Student’s t-test).

Figure 2 Lipopolysaccharide (LPS) facilitated epileptiform discharges.

Notes: (A) Mg-free artificial cerebrospinal fluid plus 4-aminopyridine (4-AP) induced epileptiform discharges in hippocampal CA1 pyramidal neurons. (B) LPS facilitated epileptiform activity; the facilitation remained 30 minutes after LPS washout. (C) Representation of the epileptiform discharges induced by Mg-free artificial cerebrospinal fluid plus 4-AP (Left) and 30 minutes after 10 μg/mL LPS added (Right). (D) Summary data (n=8) showed that LPS added after 30 minutes increased the burst counts in 5 minutes recording. (E) Expanded burst marked with black squares in (C). Notably, both frequency of burst and number of spikes per burst were increased after LPS application. (F) Summary data (n=8) showed mean counts of spikes per burst recorded in the control condition and 30 minutes after 10 μg/mL LPS was added. ***Significant difference (P<0.001; paired-sample Student’s t-test). Current clamp recordings were performed in hippocampal CA1 pyramidal neurons. Holding potential was −70 mV.

Figure 3 Lipopolysaccharide (LPS) enhanced evoked excitatory postsynaptic currents (eEPSCs) but did not modify evoked inhibitory postsynaptic currents (eIPSCs) in hippocampal CA1 pyramidal neurons.

Notes: Representative traces of eEPSC (A) and eIPSC (B) recorded in artificial cerebrospinal fluid (black lines) and 30 minutes after lipopolysaccharide was added (gray lines) under voltage clamp. Summary data depicted mean eEPSC (C) and eIPSC (D) peak amplitudes in control conditions and in the presence of lipopolysaccharide (n=5). **Significant difference (P<0.01; paired-sample Student’s t-test). Holding potential was −70 mV for recording eEPSCs and −40 mV for eIPSCs.
Abbreviation: ms, millisecond.

Figure 4 Lipopolysaccharide (LPS) enhanced excitability of hippocampal CA1 pyramidal neurons.

Notes: (A) Representative traces showed neuronal responses to a 190 pA depolarizing current for 1 second in control artificial cerebrospinal fluid (Left) and 30 minutes after LPS was added (Right). Note the enhanced neuronal excitability in the presence of LPS. (B) Graph of action potential (AP) frequency shown in mean ± standard deviation for control condition and LPS exposure. The mean action potential frequency significantly increased after LPS exposure. ^*,#Significant differences (P<0.05 and P<0.01, respectively) compared LPS with control conditions. (C) Reduction of rheobase was significant 30 minutes after LPS application (P<0.05; n=8; paired-sample Student’s t-test). (D) Representative traces showed the first action potential evoked by rheobase current in control artificial cerebrospinal fluid and 30 minutes after LPS was added. (E) Summary data showed there were not significant differences in amplitude and half-width of the first action potential under the rheobase current injection (both P>0.05; n=8; paired-sample Student’s t-test). Holding potential was −70 mV in these processes.

Abbreviation: ms, millisecond.