Peripheral immune challenge with dsRNA enhances kainic acid-induced status epilepticus

Kirschman, Lindsay T.; Borysiewicz, Elizabeth; Fil, Daniel; Konat, G.

doi:10.1007/s11011-011-9236-z

Cited by 15 publications

(23 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present study extends our previous finding that peripheral APR induced by a viral mimic, PIC, increases the susceptibility to KA-induced excitotoxicity (Kirschman et al 2011). Here, we have demonstrated that the window of increased susceptibility lasts up to 3 days after PIC challenge (Fig.…”

Section: Discussionsupporting

confidence: 91%

“…We have previously demonstrated that PIC challenge strongly enhances the susceptibility of mice to KA-induced seizures (Kirschman et al 2011). However, this feature was analyzed only 48 h after PIC injection.…”

Section: Resultsmentioning

confidence: 99%

“…Saline injected mice served as controls. Seizure severity was scored by blinded observers in 5 min intervals as described previously (Kirschman et al 2011). Cumulative seizure scores were assessed as the summation of all scores over the 2 h observation period.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, we have found that this robust, albeit generally transient, genomic response to PIC-induced APR renders the brain hypersusceptible to excitotoxic insult (Kirschman et al 2011). In this study, mice were i.p.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Peripherally restricted acute phase response to a viral mimic alters hippocampal gene expression

Michalovicz

Konat

2013

Metab Brain Dis

Self Cite

View full text Add to dashboard Cite

We have previously shown that peripherally restricted acute phase response (APR) elicited by intraperitoneal (i.p.) injection of a viral mimic, polyinosinic-polycytidylic acid (PIC), renders the brain hypersusceptible to excitotoxic insult as seen from profoundly exacerbated kainic acid (KA)-induced seizures. In the present study, we found that this hypersusceptibility was protracted for up to 72 h. RT-PCR profiling of hippocampal gene expression revealed rapid upregulation of 23 genes encoding cytokines, chemokines and chemokine receptors generally within 6 h after PIC challenge. The expression of most of these genes decreased by 24 h. However, two chemokine genes, i.e., Ccl19 and Cxcl13 genes, as well as two chemokine receptor genes, Ccr1 and Ccr7, remained upregulated for 72 h suggesting their possible involvement in the induction and sustenance of seizure hypersusceptibility. Also, 12 genes encoding proteins related to glutamatergic and GABAergic neurotransmission featured initial upregulation or downregulation followed by gradual normalization. The upregulation of the Gabrr3 gene remained upregulated at 72 h, congruent with its plausible role in the hypersusceptible phenotype. Moreover, the expression of ten microRNAs (miRs) was rapidly affected by PIC challenge, but their levels generally exhibited oscillating profiles over the time course of seizure hypersusceptibility. These results indicate that protracted seizure susceptibility following peripheral APR is associated with a robust polygenic response in the hippocampus.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Peripherally restricted acute phase response to a viral mimic alters hippocampal gene expression

Michalovicz

Konat

2013

Metab Brain Dis

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, we used a combination of pIC and PILO to induce iSE in our mouse model. The doses of pIC and PILO were decided by past studies [13][14][15][16]. Midazolam was then administered 1 h after PILO-induced seizure.…”

Section: Introductionmentioning

confidence: 99%

Benzodiazepines induce sequelae in immature mice with inflammation-induced status epilepticus

Nakajima

Hirai

Morio

et al. 2015

Epilepsy & Behavior

View full text Add to dashboard Cite

Peripheral viral challenge triggers hippocampal production of inflammatory proteins

Petrisko

Konat

2017

Metab Brain Dis

View full text Add to dashboard Cite

Peripheral viral infections increase seizure propensity and intensity in susceptible individuals. We have modeled this comorbidity by demonstrating that intraperitoneal (ip) injection of the conventional viral mimetic, polyinosinic-polycytidylic acid (PIC), renders the brain hypersusceptible to seizures induced by kainic acid (KA). At the molecular level, the hippocampus, which is the ictal site of KA-induced seizures, exhibits upregulated expression of messages encoding several inflammatory genes. Here, we profiled temporal expression of these genes at the protein level. Briefly, eight-week old female C57BL/6 mice were ip injected with 12 mg/kg of PIC and inflammatory proteins were quantified in the hippocampus and blood by ELISA. We found a robust but transient increase in blood concentration of IL-6, CXCL10, CCL2, CXCL9, CCL7 and CCL12 six hours after PIC challenge. CXCL1, IL1β, TNFα and CXCL2 featured a moderate increase. However, only four chemokines were increased in the hippocampus. CXCL10 showed the highest increase 6-12 h after PIC challenge, and its level dwindled to the baseline by 48 h. CXCL1, CXCl9 and CXCL2 were also transiently elevated but their maximal values were by an order of magnitude lower than the values for CXCL10. These results indicate that CXCL10 is the primary inflammatory protein generated in the hippocampus in response to PIC challenge, and that this chemokine may drive the development of seizure hypersusceptibility. In addition, the hippocampus featured a protracted increase in the levels of anaphylatoxins C3a and C5a, indicating the activation of the complement cascades.

show abstract

Peripheral immune challenge with dsRNA enhances kainic acid-induced status epilepticus

Cited by 15 publications

References 13 publications

Peripherally restricted acute phase response to a viral mimic alters hippocampal gene expression

Peripherally restricted acute phase response to a viral mimic alters hippocampal gene expression

Benzodiazepines induce sequelae in immature mice with inflammation-induced status epilepticus

Peripheral viral challenge triggers hippocampal production of inflammatory proteins

Contact Info

Product

Resources

About