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Intra-hippocampal injection of lipopolysaccharide inhibits kindled seizures and retards kindling rate in adult rats

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Abstract

Neuroinflammation facilitates seizure acquisition and epileptogenesis in developing brain. Yet, the studies on impact of neuroinflammation on mature brain epileptogenesis have led to inconsistent results. Hippocampus is particularly vulnerable to damage caused by ischemia, hypoxia and trauma, and the consequent neuroinflammation, which can lead in turn to epilepsy. Lipopolysaccharide (LPS) is extensively used in experimental studies to induce neuroinflammation. In this study, effect of acute and chronic intra-CA1 infusion of LPS on amygdala-kindled seizures and epileptogenesis was examined in mature rats. LPS (5 μg/rat) inhibited evoked amygdala afterdischarges and behavioral seizures. Anticonvulsant effect of LPS was observed 0.5 h after administration and continued up to 24 h. This effect was accompanied by intra-hippocampal elevation of nitric oxide (NO), interleukin1-β, and tumor necrosis factor-α and was prevented by microglia inhibitor, naloxone, NO synthase inhibitor, Nω-nitro-l-arginine methyl ester, cyclooxygenase inhibitor, piroxicam, and interleukin1-β receptor antagonist, interleukin1-ra. Moreover, daily intra-hippocampal injection of LPS significantly retarded kindling rate. In order to further elucidate the effect of LPS on synaptic transmission and short-term plasticity, changes in field excitatory postsynaptic potentials and population spikes were measured in stratum radiatum and stratum pyramidale of LPS-treated kindled rats. LPS impaired baseline synaptic transmission in hippocampal Schaffer collateral-CA1 synapse and reduced the magnitude of paired-pulse facilitation. Our results suggest that direct suppression of presynaptic mechanisms in Schaffer collateral-CA1 synapses, as well as the inflammatory mediators released by LPS in the hippocampus, is involved in antiepileptic effect of LPS.

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Abbreviations

LPS:

Lipopolysaccharide

NO:

Nitric oxide

IL-1β:

Interleukin1-β

TNF-α:

Tumor necrosis factor-α

IL-1ra:

Interleukin1ra

l-NAME:

N ω-nitro-l-arginine methyl ester

i.h:

Intra-hippocampal

i.p:

Intra-peritoneally

AD:

Afterdischarge

ADD:

AD duration

SS:

Behavioral seizure severity

S5D:

Duration of stage 5 seizure behavior

SD:

Duration of seizure behavior

fEPSP:

Field excitatory postsynaptic potential

PS:

Population spike

PPI:

Paired-pulse index

PPF:

Paired-pulse facilitation

TGF-β1:

Transforming growth factor-β1

PTZ:

Pentylenetetrazole

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None of authors has any conflict of interest to disclose. We confirm that we have read Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Pasteur Institute of Iran, Pasteur Avenue, 1316943551, Tehran, Iran

    Amin Ahmadi, Mohammad Sayyah, Baharak Khoshkholgh-Sima, Samira Choopani, Jafar Kazemi & Farshad Moradpour

  2. School of Biology, College of Science, University of Tehran, Tehran, Iran

    Amin Ahmadi

  3. Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Mehdi Sadegh & Farshad Moradpour

  4. Department of Parasitology, Pasteur Institute of Iran, Tehran, Iran

    Hossein Nahrevanian

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  1. Amin Ahmadi
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  2. Mohammad Sayyah
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Correspondence to Mohammad Sayyah.

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Ahmadi, A., Sayyah, M., Khoshkholgh-Sima, B. et al. Intra-hippocampal injection of lipopolysaccharide inhibits kindled seizures and retards kindling rate in adult rats. Exp Brain Res 226, 107–120 (2013). https://doi.org/10.1007/s00221-013-3415-6

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