The bacterial endotoxin lipopolysaccharide enhances seizure susceptibility in mice: involvement of proinflammatory factors: nitric oxide and prostaglandins

Sayyah, Mohammad; Javadpour, Mohsen; Ghazi‐Khansari, Mahmoud

doi:10.1016/j.neuroscience.2003.08.043

Cited by 147 publications

(89 citation statements)

References 45 publications

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“…The primary impact of our observations is that an isolated hippocampus taken from an animal with intestinal inflammation is significantly more excitable than one taken from a control animal. Thus, the presence of peripheral inflammation that alters the intrinsic CNS excitability and the increased seizure susceptibility we and others (37)(38)(39)(40) have observed in vivo cannot be explained by either increased access of the convulsant to the brain, or other alterations in the physiology (temperature, other circulating factors) of the intact animal.…”

Section: Discussionmentioning

confidence: 75%

Microglial activation and TNFα production mediate altered CNS excitability following peripheral inflammation

Riazi

Galic²,

Kuzmiski³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

362

307

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Peripheral inflammation leads to a number of centrally mediated physiological and behavioral changes. The underlying mechanisms and the signaling pathways involved in these phenomena are not yet well understood. We hypothesized that peripheral inflammation leads to increased neuronal excitability arising from a CNS immune response. We induced inflammation in the gut by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) to adult male rats. To examine the excitability of the brain in vivo, we administered pentylenetetrazole (PTZ; a GABAergic antagonist) intravenously to evoke clonic seizures. Rats treated with TNBS showed increased susceptibility to PTZ seizures that was strongly correlated with the severity and progression of intestinal inflammation. In vitro hippocampal slices from inflamed, TNBS-treated rats showed increased spontaneous interictal burst firing following application of 4-aminopyridine, indicating increased intrinsic excitability. The TNBS-treated rats exhibited a marked, reversible inflammatory response within the hippocampus, characterized by microglial activation and increases in tumor necrosis factor ␣ (TNF␣) levels. Central antagonism of TNF␣ using a monoclonal antibody or inhibition of microglial activation by i.c.v. injection of minocycline prevented the increase in seizure susceptibility. Moreover, i.c.v. infusion of TNF␣ in untreated rats for 4 days also increased seizure susceptibility and thus mimicked the changes in seizure threshold observed with intestinal inflammation. Our finding of a microglia-dependent TNF␣-mediated increase in CNS excitability provides insight into potential mechanisms underlying the disparate neurological and behavioral changes associated with chronic inflammation.4-aminopyridine ͉ cytokine ͉ pentylenetetrazole ͉ seizure ͉ colitis

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Section: Discussionmentioning

confidence: 75%

Microglial activation and TNFα production mediate altered CNS excitability following peripheral inflammation

Riazi

Galic²,

Kuzmiski³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

362

307

View full text Add to dashboard Cite

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“…It was demonstrated that (i) LPS and pro-inflammatory cytokines can induce the expression of COX-2 mRNA (Cao et al, 1995;Vezzani and Granata, 2005), (ii) prostaglandins may have a role in the seizure threshold decreasing effect of LPS (Sayyah et al, 2003), (iii) PGE 2 has proconvulsant effect (Sayyah et al, 2003) and (iv) the T-type Ca 2+ channel evoked Ca 2+ current (which has a role in the genesis of absence seizure) decreasing effect of IND may diminish absence epileptic activity in WAG/Rij rats, GAERS rats and Long Evans rats (Depaulis and Van Luijtelaar, 2005;Polack and Charpier, 2006;Shin, 2006;Van Luijtelaar et al, 2000). Thus, indomethacin may exert its effect on absence epileptic activity (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Changes in IL-1␤ and TNF-␣ levels may have a role in SWD generation/precipitation in two animal models of human absence epilepsy, GAERS rats and WAG/Rij rats (Akin et al, 2011;Van Luijtelaar et al, 2012). Lipopolysaccharide evokes rapid excitation in the cortex (Wang and White, 1999), enhances seizure susceptibility (Sayyah et al, 2003), increases absence epileptic activity and body temperature (Kovács et al, 2006(Kovács et al, , 2011 brain (Györffy et al, 2014). These effects of LPS may be mediated by increased levels of pro-inflammatory cytokines and interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) signaling in the CNS (Turrin et al, 2001;Vezzani et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide induced increase in seizure activity in two animal models of absence epilepsy WAG/Rij and GAERS rats and Long Evans rats

Kovács

Dobolyi

Juhász

et al. 2014

Brain Research Bulletin

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Absence epileptic rats a b s t r a c tWe showed previously that the number and time of spike-wave discharges (SWDs) were increased after intraperitoneal (i.p.) injection of lipopolysaccharide (LPS), an effect, which was completely abolished by cyclooxygenase-2 (COX-2) inhibitor indomethacin (IND) pretreatment in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. These and other results suggest that injection of LPS to genetically absence epileptic animals, such as WAG/Rij rats, may allow us to investigate relationships between absence epilepsy and LPS evoked neuroinflammation processes. However, LPS may evoke different effects on absence epileptic activity in various animal strains. Thus, to extend our previous results, we injected two doses of LPS (50 g/kg and 350 g/kg i.p.) alone and in combination with IND (10 mg/kg IND i.p. +50 g/kg LPS) into rats of two model animal strains (WAG/Rij rats; GAERS rats: Genetic Absence Epileptic Rats from Strasbourg) and into Long Evans rats. The effects of treatments on SWD number and SWD duration were examined. Both doses of LPS increased the SWD number and the total time of SWDs dose-dependently during the whole 4-h recording period, which was abolished by IND pretreatment in all three investigated strains. These results extend our previous results suggesting that our methods using LPS injection into freely moving absence epileptic rats is applicable not only in well-established animal models of absence epilepsy such as WAG/Rij rats and GAERS rats but also in Long Evans rats to investigate links between inflammation and absence epilepsy.

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“…In this respect, systemic administration of LPS to mice was reported to decrease their threshold to pentylenetetrazole-induced seizures, and this effect was blocked by antiinflammatory drugs (32). Finally, sequential infusion of individual proteins of the membrane attack complex (MAC) of the complement system into the rat hippocampus induced both behavioral and electrographic seizures and cytotoxicity (33).…”

Section: Functional Studies: Effect Of Proinflammatory Molecules On Smentioning

confidence: 99%

Inflammation and epilepsy

Vezzani

Balosso

Ravizza

2012

Handbook of Clinical Neurology

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The bacterial endotoxin lipopolysaccharide enhances seizure susceptibility in mice: involvement of proinflammatory factors: nitric oxide and prostaglandins

Cited by 147 publications

References 45 publications

Microglial activation and TNFα production mediate altered CNS excitability following peripheral inflammation

Microglial activation and TNFα production mediate altered CNS excitability following peripheral inflammation

Lipopolysaccharide induced increase in seizure activity in two animal models of absence epilepsy WAG/Rij and GAERS rats and Long Evans rats

Inflammation and epilepsy

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