| First Author | Feng B | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 21931 | PubMed ID | 26902320 |
| Mgi Jnum | J:287410 | Mgi Id | MGI:6407550 |
| Doi | 10.1038/srep21931 | Citation | Feng B, et al. (2016) Transient increase of interleukin-1beta after prolonged febrile seizures promotes adult epileptogenesis through long-lasting upregulating endocannabinoid signaling. Sci Rep 6:21931 |
| abstractText | It remains unclear how infantile febrile seizures (FS) enhance adult seizure susceptibility. Here we showed that the transient increase of interleukin-1beta (IL-1beta) after prolonged FS promoted adult seizure susceptibility, which was blocked by interleukin-1 receptor antagonist (IL-1Ra) within a critical time window. Postnatal administered IL-1beta alone mimicked the effect of FS on adult seizure susceptibility. IL-1R1 knockout mice were not susceptible to adult seizure after prolonged FS or IL-1beta treatment. Prolonged FS or early-life IL-1beta treatment increased the expression of cannabinoid type 1 receptor (CB1R) for over 50 days, which was blocked by IL-1Ra or was absent in IL-1R1 knockout mice. CB1R antagonist, knockdown and endocannabinoid synthesis inhibitor abolished FS or IL-1beta-enhanced seizure susceptibility. Thus, this work identifies a pathogenic role of postnatal IL-1beta/IL-1R1 pathway and subsequent prolonged prominent increase of endocannabinoid signaling in adult seizure susceptibility following prolonged FS, and highlights IL-1R1 as a potential therapeutic target for preventing the development of epilepsy after infantile FS. |
