Elsevier

Neuroscience

Volume 122, Issue 4, 2003, Pages 1073-1080
Neuroscience

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

https://doi.org/10.1016/j.neuroscience.2003.08.043Get rights and content

Abstract

Central nervous system (CNS) inflammation in cases such as head trauma, infection and stroke has been associated with the occurrence of epileptic seizures. Microglia, the principal immune cells in the brain, readily become activated in response to injury, infection or inflammation. The bacterial endotoxin lipopolysaccharide (LPS) induces the activation of microglia and the production of proinflammatory factors including nitric oxide (NO) and prostaglandins (PGs). We examined the effect of LPS on seizure susceptibility of mice, by using the sensitive test, threshold of clonic seizures induced by i.v. infusion of pentylenetetrazole. LPS decreased the seizure threshold in a dose- and time-dependent manner. Pretreatment of mice with the NO synthase inhibitor, NG-nitro-l-arginine methyl ester or cyclooxygenase inhibitor, piroxicam or the opioid receptor antagonist, (−)-naloxone completely reversed the proconvulsant effect of LPS.

These results indicate that NO, PGs and endogenous opioid peptides seem to be involved in LPS-induced decrease in seizure threshold.

Section snippets

Animals

Adult male NMRI mice, 28–35 days old, weighing 20–28 g, from Institute Pasteur of Iran (Tehran, Iran; n=600) were used throughout this study. The animals were housed in standard Plexiglas cages with free access to food (standard laboratory rodent's chow) and water. The animal house temperature was maintained at 23±3.0 °C with a 12-h light/dark cycle (light on from 6:00 AM). All animal experiments were carried out in accordance with the European Communities Council Directive in such a way to

Effect of LPS on body temperature

During the 8-h recording, there was a gradual decrease in body temperature of the mice receiving no injection or saline (control group). There was no difference in body temperature of both groups in different recording times. Therefore, only the results of saline group are shown in Fig. 1. Moreover, Fig. 1 demonstrates that LPS (1 mg/kg, i.p.) produces significant hypothermia at 1 h after administration where the mice body temperature is 36.6±0.2 °C compared with saline group (37.4±0.1 °C) at

Discussion

Seizures and epilepsy are common sequels to acute brain insults such as stroke, traumatic brain injury and infection Temkin et al., 2001, Herman, 2002 where there is a certain CNS inflammatory processes Willmore, 1990, Thompson et al., 1993, Li et al., 1997, Leib et al., 1998. Microglia are the principal immune cells in the brain and they become activated in response to injury, infection or inflammation Kreutzberg, 1996, Streit et al., 1998. The bacterial endotoxin LPS is a general inflammatory

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      It should also be mentioned that seizures also exacerbate neuroinflammation and can upregulate the inflammatory system. Experimental studies conducted on dose-dependent and age-dependent, peripheral administration of LPS have shown increased seizure events following the activation of TLR-4 by LPS’ ability to mimic the high mobility group box one protein (HMGB1) that is known to promote seizures [103]. It is also important to mention that neuroinflammation caused by mild TBI can induce seizures through the overexpression of inflammatory proteins [104–105].

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