Experimental Brain Research

, Volume 226, Issue 1, pp 107–120 | Cite as

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

  • Amin Ahmadi
  • Mohammad Sayyah
  • Baharak Khoshkholgh-Sima
  • Samira Choopani
  • Jafar Kazemi
  • Mehdi Sadegh
  • Farshad Moradpour
  • Hossein Nahrevanian
Research Article


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.


Schaffer collateral-CA1 synapse Neuroinflammation Lipopolysacharide Epileptogenesis 





Nitric oxide




Tumor necrosis factor-α




N ω-nitro-l-arginine methyl ester








AD duration


Behavioral seizure severity


Duration of stage 5 seizure behavior


Duration of seizure behavior


Field excitatory postsynaptic potential


Population spike


Paired-pulse index


Paired-pulse facilitation


Transforming growth factor-β1




Conflict of interest

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Amin Ahmadi
    • 1
    • 2
  • Mohammad Sayyah
    • 1
  • Baharak Khoshkholgh-Sima
    • 1
  • Samira Choopani
    • 1
  • Jafar Kazemi
    • 1
  • Mehdi Sadegh
    • 3
  • Farshad Moradpour
    • 1
    • 3
  • Hossein Nahrevanian
    • 4
  1. 1.Department of Physiology and PharmacologyPasteur Institute of IranTehranIran
  2. 2.School of Biology, College of ScienceUniversity of TehranTehranIran
  3. 3.Department of Physiology, School of Medical SciencesTarbiat Modares UniversityTehranIran
  4. 4.Department of ParasitologyPasteur Institute of IranTehranIran

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