Epilepsy and brain inflammation

Vezzani, Annamaria; Aronica, Eleonora; Mazarati, Andréy; Pittman, Quentin J.

doi:10.1016/j.expneurol.2011.09.033

Cited by 510 publications

(422 citation statements)

References 192 publications

Supporting

Mentioning

402

Contrasting

Unclassified

Order By: Relevance

“…Lipopolysaccharide evoked increased expression in TLR4, IL-1␤ and TNF-␣ in the brain within several hours (Eriksson et al, 2000;Goralski et al, 2005;Turrin et al, 2001;Vezzani et al, 2011) and glial release of proinflammatory cytokines (e.g., IL-1␤ and TNF-␣) through TLR4 was also demonstrated (Mlodzikowska-Albrecht et al, 2007;Rodgers et al, 2009;Vezzani et al, 2011). IL-1␤ and TNF-␣ may diminish the chloride current and may enlarge excitatory glutamatergic neurotransmission (Mlodzikowska-Albrecht et al, 2007;Vezzani and Granata, 2005) causing decreased seizure threshold and enhanced neuronal hyperexcitability (Riazi et al, 2010;Rodgers et al, 2009;Vezzani et al, 2011Vezzani et al, , 2013. In addition, GABA (A) -mediated inhibition decreasing influence and AMPA-dependent excitation increasing effect of TNF-␣ were also demonstrated (Mlodzikowska-Albrecht et al, 2007;Vezzani et al, 2008).…”

Section: Discussionmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

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

View full text Add to dashboard Cite

show abstract

“…Accordingly, based on this background, it is not possible to exclude that fingolimod can exert antiepileptogenic effects in this strain through some kind of antiinflammatory mechanisms, which could also be linked to a modulation of neuronal S1P receptors [13]. It is known that glial activation and the related overexpression of proinflammatory cytokines seem to play a crucial role in epileptogenesis both in humans and in several animal models of epilepsy [58][59][60][61]; however, to date, such a relationship between neuroinflammation and absence seizure development in WAG/Rij rats remains unclear [27,28]. Indeed, neuroinflammation and related mediators worsen absence seizures in this strain [28-30, 62, 63], while cyclooxygenase inhibitors have some partial antiabsence properties [11,63,64] and etoricoxib, a selective COX-2 inhibitor, also possesses antiepileptogenic effects in this strain, which appear to be more effective than fingolimod with a reduction in the development of absence seizures of about 45% vs 30% obtained with fingolimod [11].…”

Section: Discussionmentioning

confidence: 99%

Fingolimod Exerts only Temporary Antiepileptogenic Effects but Longer-Lasting Positive Effects on Behavior in the WAG/Rij Rat Absence Epilepsy Model

et al. 2017

View full text Add to dashboard Cite

One of the major challenges in the epilepsy field is identifying disease-modifying drugs in order to prevent or delay spontaneous recurrent seizure onset or to cure already established epilepsy. It has been recently reported that fingolimod, currently approved for the treatment of relapsing-remitting multiple sclerosis, has demonstrated antiepileptogenic effects in two different preclinical models of acquired epilepsy. However, to date, no data exist regarding the role of fingolimod against genetic epilepsy. Therefore, we have addressed this issue by studying the effects of fingolimod in WAG/Rij rats, a well-established genetic model of absence epilepsy, epileptogenesis, and neuropsychiatric comorbidity. Our results have demonstrated that an early-long term treatment with fingolimod (1 mg/Kg/day), started before absence seizure onset, has both antiepileptogenic and antidepressant-like effects in the WAG/Rij rats. However, these effects were transitory, since 5 months after treatment discontinuation, both absence seizure and depressive like-behavior returned to control level.Furthermore, a temporary reduction of mTOR signaling pathway activity, indicated by reduced p-mTOR and p-p70S6k levels and by an increased p-AKT in WAG/Rij rats of 6 months of age accompanied the transitory antiepileptogenic fingolimod effects. Surprisingly, fingolimod has demonstrated longer-lasting positive effects on cognitive decline in this strain. This effect was accompanied by an increased acetylation of Lysine 8 of histone H4 (both 6 and 10 months of age). In conclusion, our results support the antiepileptogenic effects fingolimod. However, these antiepileptogenic effects were transitory. Moreover, fingolimod might also have a positive impact on animal behavior and particularly in protecting the development of memory decline.

show abstract

“…Several studies using an experimental animal model of epilepsy revealed that the effects of brain inflammation contribute to the generation of individual seizures and cell death, which, in turn, activates further inflammation, thereby establishing a vicious circle of events that contributes to the development of epilepsy. 39) In animal models of temporal lobe epilepsy induced by intrahippocampal or intraperitoneal injection of kainic acid (KA), an agonist of non-N-methyl-D-aspartate (non-NMDA) ionotropic glutamate receptors, COX-2 expression was shown to be increased immediately in hippocampal neurons and gradually in nonneuronal cells, such as endothelia and astrocytes, after induction of seizures. 40) The PGE 2 level was also increased in the hippocampus after KA-induced seizures.…”

Section: Role Of Mpges-1 In Epilepsymentioning

confidence: 99%

The Role of mPGES-1 in Inflammatory Brain Diseases

Ikeda‐Matsuo

2017

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Prostaglandin E 2 (PGE 2 ) has been thought to be an important mediator of inflammation in peripheral tissues, but recent studies clearly show the involvement of PGE 2 in inflammatory brain diseases. In some animal models of brain disease, the genetic disruption and chemical inhibition of cyclooxygenase (COX)-2 resulted in the reduction of PGE 2 and amelioration of symptoms, and it had been thought that PGE 2 produced by COX-2 may be involved in the progression of injuries. However, COX-2 produces not only PGE 2 , but also some other prostanoids, and thus the protective effects of COX-2 inhibition, as well as severe side effects, may be caused by the inhibition of prostanoids other than PGE 2 . Therefore, to elucidate the role of PGE 2 , studies of microsomal prostaglandin E synthase-1 (mPGES-1), an inducible terminal enzyme for PGE 2 synthesis, have recently been an active area of research. Studies from mPGES-1 deficient mice provide compelling evidence for its role in a variety of inflammatory brain diseases, such as ischemic stroke, Alzheimer's disease and epilepsy, and clues for developing new therapeutic treatments for brain diseases by targeting mPGES-1. Considering that COX inhibitors may non-selectively suppress the production of many types of prostanoids that are essential for normal physiological functioning of the brain and peripheral tissues, as well as induce gastro-intestinal, renal and cardiovascular complications, mPGES-1 inhibitors are expected to be injury-selective and have fewer side-effects when treating human brain diseases. Thus, this paper focuses on recent studies that have demonstrated the involvement of mPGES-1 in pathological brain diseases.

show abstract

Epilepsy and brain inflammation

Cited by 510 publications

References 192 publications

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

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

Fingolimod Exerts only Temporary Antiepileptogenic Effects but Longer-Lasting Positive Effects on Behavior in the WAG/Rij Rat Absence Epilepsy Model

The Role of mPGES-1 in Inflammatory Brain Diseases

Contact Info

Product

Resources

About