The Role of NLRP3 and IL-1β in Refractory Epilepsy Brain Injury

Abstract

The objective of this study was to investigate the roles and mechanisms of inflammatory mediators NLRP3 and IL-1β in refractory temporal epilepsy brain injury. Method: First, the brain tissue and the peripheral blood of children undergoing intractable temporal lobe epilepsy surgery were analyzed as research objects. The expression levels of NLRP3 in brain tissue and IL-1β in blood were measured. A model of temporal lobe epilepsy was established using wild-type and NLRP3 knockout 129 mice. Pilocarpine was injected intraperitoneally into the experimental group, and isovolumetric saline was injected intraperitoneally into the control group (n = 8 in each group). The expression of IL-1β in the peripheral blood, cerebral cortex, and hippocampus of mice was measured by ELISA at 3 h, 24 h, 3 days, and 7 days after modeling. Fluoro-Jade B (FJB) and TUNEL methods were used to determine necrosis and apoptosis in hippocampal neurons, respectively, and the expression of NLRP3 in the cortex was measured by immunofluorescence methods. Result: (1) The IL-1β levels in the peripheral blood of children with intractable temporal lobe epilepsy were higher than those in the control group (t = 2.813, P = 0.01). There was also a positive correlation between IL-1β expression levels and the onset time of a single convulsion in patients with refractory epilepsy (r = 0.9735, P < 0.05). The expression level of NLRP3 in the cerebral cortex of patients with refractory temporal lobe epilepsy was higher than that in the control group. (2) The expression level of NLRP3 in the hippocampus of wild-type mice increased 3 days after modeling and decreased slightly at 7 days but remained higher than that of the control group. IL-1β levels in peripheral blood were significantly higher than those in the control group at 3 days (t = 8.259, P < 0.0001). The IL-1β levels in the peripheral blood of NLRP3 knockout mice were lower than those in the wild-type group at 3 days (t = 3.481, P = 0.004). At day 7, the neuronal necrosis and apoptosis levels in the CA3 region of the hippocampus decreased. Conclusion: NLRP3 may be involved in the development of refractory temporal lobe epilepsy. Inhibiting NLRP3 may alleviate local brain injury by downregulating the IL-1β expression. The IL-1β levels in the peripheral blood of patients with refractory temporal lobe epilepsy may reflect the severity of convulsions.

Implication of metabolic and dopamine transporter PET in dementia with Lewy bodies

“…Both DLB and control groups had AI values suggesting rightward asymmetry, while the DLB group had higher absolute AI values than the control group (Table 1 ). These results are consistent with Chen’s previous study showing that DLB patients have significantly higher absolute AI values than controls, along with significant rightward asymmetry in terms of local and global network efficiency 31 . However, the controls in the previous study had no asymmetry in terms of global and local network efficiency, while our control group had significant rightward metabolic asymmetry.…”

“…Different methodology of network analysis in the previous study could be a reason for the different laterality in our control subjects. Although the previous study showed that PD dementia (leftward asymmetry) and DLB (rightward asymmetry) patients had different asymmetric patterns in local efficiency 31 , more frequent mixed AD pathology in the DLB group than in the PD dementia group could have contributed to the different laterality 32 . Also, an increased absolute AI was shown to be characteristic of PD dementia, as well as DLB, in the previous study 31 , and PC1 well explained the increased absolute AI in our DLB patients (Supplementary Table 4 ).…”

Semaglutide attenuates seizure severity and ameliorates cognitive dysfunction by blocking the NLR family pyrin domain containing 3 inflammasome in pentylenetetrazole‑kindled mice

“…Semaglutide decreases inflammatory cytokine secretion in PTZ-kindled mice. In various respects, inflammasome activation contributes to the release of inflammatory cytokines, which play a pivotal role in epileptogenesis (14,15,38). The present study demonstrated that semaglutide blocked NLRP3 inflammasome activation.…”

“…The NLRP3 inflammasome results from the assembly of NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and caspase-1 (14), and promotes the secretion of inflammatory cytokines, influencing the pathophysiology of epilepsy (14). Additionally, in animal and clinical epilepsy-related research, increased levels of the NLRP3 inflammasome and neuroinflammatory cytokines have been detected in hippocampal tissues (15,16), suggesting their close association with epileptogenesis. Moreover, numerous studies have reported that inhibiting NLRP3 activation and inflammatory cytokine secretion decreases to occurrence of epileptic seizures and ameliorates cognitive dysfunction (17,18).…”

Comparison of multiplex cytokine assays in a pediatric cohort with epilepsy

“…One to three milliliters of whole blood were drawn by peripheral venipuncture into a K 2 -EDTA vacutainer tube. Plasma collection was selected to optimize yield of cytokines of interest in epilepsy, in particular those within the IL-1 family and NLRP3 inflammasome signaling pathways including IL-1β and IL-6 ( de Jager et al., 2009 ; Ulusoy et al., 2020 ; Wu et al., 2019 ). Within one hour of collection ( Henno et al., 2017 ), blood was centrifuged for 10 minutes at 1,300 g at 4°C, the supernatant transferred to a separate tube, and then centrifuged for 10 minutes at 16,000 g at 4°C.…”