Effects of HI 6, Diazepam and Atropine on Soman-Induced IL-1β Protein in Rat Brain

Svensson, Ingrid; Waara, Lena; Cassel, Gudrun

doi:10.1016/j.neuro.2004.11.004

Cited by 24 publications

(21 citation statements)

References 30 publications

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“…1a). The extensive activation of inflammatory responses in the seizing rats, in particular by neurotoxic and pro-inflammatory cytokines, such as Il-1β, Tnf-α, and Il-6, was observed in all brain regions (Spradling et al, 2011a(Spradling et al, , 2011b, consistent with findings from previous studies (Chapman et al, 2006;Dhote et al, 2007;Dillman et al, 2009;Johnson and Kan, 2010;Svensson et al, 2001Svensson et al, , 2005Williams et al, 2003).…”

Section: Introductionsupporting

confidence: 91%

“…Further evidence of the role of Il-1β is its significantly higher and longer-lasting levels of expression in rats experiencing longer seizures (Chapman et al, 2006), and its involvement in longterm brain damage after OP intoxication (Svensson et al, 2001). Importantly, animals that do not exhibit seizures following soman intoxication did not over-express Il-1β (Svensson et al, 2005).…”

Section: Differential Activation Of Mapk Sub-pathways Distinguished Tmentioning

confidence: 99%

“…4b), and notably absent in the non-seizing group, serve as the potential trigger of the JNK and p38 MAPK signaling sub-pathway in OP-induced seizures (Chapman et al, 2006;Dhote et al, 2007;Johnson and Kan, 2010;Svensson et al, 2001Svensson et al, , 2005Williams et al, 2003). Further evidence of the role of Il-1β is its significantly higher and longer-lasting levels of expression in rats experiencing longer seizures (Chapman et al, 2006), and its involvement in longterm brain damage after OP intoxication (Svensson et al, 2001).…”

Section: Differential Activation Of Mapk Sub-pathways Distinguished Tmentioning

confidence: 99%

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Neuroprotective mechanisms activated in non-seizing rats exposed to sarin

Spradling-Reeves

Dillman

et al. 2015

Brain Research

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Exposure to organophosphate (OP) nerve agents, such as sarin, may lead to uncontrolled seizures and irreversible brain injury and neuropathology. In rat studies, a median lethal dose of sarin leads to approximately half of the animals developing seizures. Whereas previous studies analyzed transcriptomic effects associated with seizing sarin-exposed rats, our study focused on the cohort of sarin-exposed rats that did not develop seizures. We analyzed the genomic changes occurring in sarin-exposed, non-seizing rats and compared differentially expressed genes and pathway activation to those of seizing rats. At the earliest time point (0.25 h) and in multiple sarin-sensitive brain regions, defense response genes were commonly expressed in both groups of animals as compared to the control groups. All sarin-exposed animals activated the MAPK signaling pathway, but only the seizing rats activated the apoptotic-associated JNK and p38 MAPK signaling sub-pathway. A unique phenotype of the non-seizing rats was the altered expression levels of genes that generally suppress inflammation or apoptosis. Importantly, the early transcriptional response for inflammation- and apoptosis-related genes in the thalamus showed opposite trends, with significantly down-regulated genes being up-regulated, and vice versa, between the seizing and non-seizing rats. These observations lend support to the hypothesis that regulation of anti-inflammatory genes might be part of an active and sufficient response in the non-seizing group to protect against the onset of seizures. As such, stimulating or activating these responses via pretreatment strategies could boost resilience against nerve agent exposures.

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Section: Introductionsupporting

confidence: 91%

Section: Differential Activation Of Mapk Sub-pathways Distinguished Tmentioning

confidence: 99%

Section: Differential Activation Of Mapk Sub-pathways Distinguished Tmentioning

confidence: 99%

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Neuroprotective mechanisms activated in non-seizing rats exposed to sarin

Spradling-Reeves

Dillman

et al. 2015

Brain Research

View full text Add to dashboard Cite

show abstract

“…* α < 0.05; ** α < 0.01; *** α < 0.001. neurotoxic and repair processes (Allan and Rothwell, 2001;Wang and Shuaib, 2002). Neuro-inflammatory response has been described in different models of chemically induced seizures such as those produced by kainate (Vezzani et al, 1999) and lithium-pilocarpine (Voutsinos-Porche et al, 2004) as well as by organophosphorus NA such as sarin (Chapman et al, 2006) and soman (Svensson et al, 2001(Svensson et al, , 2005Williams et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Some data also suggest a peripheral recruitment of immune cells of unknown importance (Zimmer et al, 1997b;Baille et al, 2005). Other recent studies, restricted to the most acute phase of the intoxication, have shown an early and transitory induction (<48 h) of several neuro-inflammatory genes and IL-1␤ protein (Svensson et al, 2001(Svensson et al, , 2005Williams et al, 2003). Owing to the known relationship between the cellular (glial) and molecular components of neuroinflammation, the transient gene activation described by Williams et al (2003) and Svensson et al (2001) appears rather surprising.…”

Section: Introductionmentioning

confidence: 99%