Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats

Galic, Michael A.; Riazi, Kiarash; Heida, James G.; Mouihate, Abdeslam; Fournier, Neil M.; Spencer, Sarah J.; Kalynchuk, Lisa E.; Teskey, G. Campbell; Pittman, Quentin J.

doi:10.1523/jneurosci.1901-08.2008

Cited by 263 publications

(234 citation statements)

References 88 publications

(91 reference statements)

Supporting

Mentioning

219

Contrasting

Order By: Relevance

“…These data are in agreement with a previous study where STAT3 was not expressed in neurons of mouse fetal brain (23). Furthermore, we have previously shown that activation of TLR4 at a neonatal period led to an enhanced number of astrocytes in a sub-region of the hippocampus during adulthood (25). Whether such sustained enhanced expression of astrocytes occurs in rats prenatally exposed to TLR4 …”

Section: Articles Mouihate and Mehdawisupporting

confidence: 93%

“…This mild activation of the maternal innate immune response is associated with no overt deleterious effect on either pups survival (Figure 7 in the present paper) and (34) or neural cell death in the developing brain. However, administration of larger doses of LPS has been shown to enhance pups mortality and neural cell death in the brains of surviving pups (25). The absence of overt neural cell death in the fetal brains suggests that the long lasting impact of prenatal TLR4-mediated immune stress is probably induced through a rather subtle change in neuronal/glial imbalance.…”

Section: Maternal Immune Stress and Neural Cell Death In The Fetal Brainmentioning

confidence: 99%

See 1 more Smart Citation

Toll-like receptor 4-mediated immune stress in pregnant rats activates STAT3 in the fetal brain: role of interleukin-6

Mouihate

Mehdawi

2015

Pediatr Res

View full text Add to dashboard Cite

Background: Prenatal exposure to pathogens induces long lasting effect on brain function and plasticity. It is unclear how maternal immune stress impacts fetal brain development. Immune challenged pregnant rats induce the production of inflammatory cytokines including tumor necrosis factor (TNF)α, interleukin (IL)1β, and IL-6. IL-6 crosses the placenta but its mechanism of action on fetal brain is unclear. Methods: Gestation day 15 (GD15) rats were given a single injection of lipopolysaccharide (LPS) (100 µg/kg) in the presence or the absence of an IL-6 neutralizing antibody (IL-6Ab, 10 µg/kg). The activation of the intracellular signal of IL-6; signal transducer and activator of transcription (STAT3) and levels of glucocorticoids (GCs) were monitored in fetal brains. results: LPS administration to GD15 rats significantly increased the phosphorylation levels of STAT3 in fetal brains. Such activation was blunted by IL-6Ab. LPS induced a significant rise in GCs in the plasma of dams but not in fetal brains. IL-6Ab significantly reduced LPS-induced GCs in maternal plasma. conclusion: Toll-like receptor 4 (TLR4)-induced activation of the maternal innate immune system affects fetal brains likely via the mobilization of IL-6/STAT3 pathway. In contrast, TLR4-stimulated maternal GCs release is less likely to play a significant role in fetal brain development.

show abstract

Section: Articles Mouihate and Mehdawisupporting

confidence: 93%

Section: Maternal Immune Stress and Neural Cell Death In The Fetal Brainmentioning

confidence: 99%

Toll-like receptor 4-mediated immune stress in pregnant rats activates STAT3 in the fetal brain: role of interleukin-6

Mouihate

Mehdawi

2015

Pediatr Res

View full text Add to dashboard Cite

show abstract

“…A recording electrode was placed in the CA1 stratum pyramidale to record spontaneous epileptiform discharges elicited by perfusion of the slice for 30 min with 100 M 4-AP (19). The mean frequency of the 4-AP-induced interictal discharges was used as an index of slice excitability (20,21). In slices from both control (n ϭ 7) and TNBS-treated (n ϭ 8) animals, 4-AP induced spontaneous interictal bursting (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…3A). Next we determined whether increased levels of central cytokines were responsible for the increased seizure susceptibility by interfering with their action using blockers at doses previously found to be effective (20,24). Daily i.c.v.…”

Section: Resultsmentioning

confidence: 99%

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.

366

307

View full text Add to dashboard Cite

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

show abstract

“…It has been shown that enhanced pro-inflammatory cytokine levels can increase the susceptibility to epileptic seizure (Galic et al, 2008;Vezzani et al, 2008). Indeed, pro-inflammatory cytokines (e.g., interleukin-1 ␤ (IL-1␤) and tumor necrosis factor-␣ (TNF-␣)) synthesized by glial cells in the central nervous system (CNS) elevate neuronal excitability (Rodgers et al, 2009;Vezzani et al, 2008;Vezzani and Granata, 2005).…”

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

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

Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats

Cited by 263 publications

References 88 publications

Toll-like receptor 4-mediated immune stress in pregnant rats activates STAT3 in the fetal brain: role of interleukin-6

Toll-like receptor 4-mediated immune stress in pregnant rats activates STAT3 in the fetal brain: role of interleukin-6

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

Contact Info

Product

Resources

About