Intra-hippocampal injection of lipopolysaccharide inhibits kindled seizures and retards kindling rate in adult rats.
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.
Department of Physiology and Pharmacology, Pasteur Institute of Iran, Pasteur Avenue, 1316943551 Tehran, Iran.
Amin
A
Ahmadi
Mohammad
M
Sayyah
Baharak
B
Khoshkholgh-Sima
Samira
S
Choopani
Jafar
J
Kazemi
Mehdi
M
Sadegh
Farshad
F
Moradpour
Hossein
H
Nahrevanian
D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000503:physiopathology* / Q000517:prevention & control*; D013997:Time Factors
D008070:Lipopolysaccharides