Ibuprofen Exerts Antiepileptic and Neuroprotective Effects in the Rat Model of Pentylenetetrazol-Induced Epilepsy via the COX-2/NLRP3/IL-18 Pathway

Li, Rui; Wu, Shuai; Guo, Chong; Hu, Zhongbo; Peng, Jiangtao; Guo, Ke; Zhang, Xinfan; Li, Jianmin

doi:10.1007/s11064-020-03109-9

Cited by 39 publications

(22 citation statements)

References 43 publications

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“…Another study found that GLP-1 agonists alleviated inflammation and attenuated peripheral nerve injury via the p38 MAPK/NF-κB pathway (46). A previous study also indicated that ibuprofen has antiepileptic and neuroprotective effects through the cyclooxygenase-2/NLRP3 pathway in PTZ-kindled mice (18). However, further research is necessary to clarify the precise mechanisms.…”

Section: Discussionmentioning

confidence: 97%

“…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). These findings suggest that inhibition of NLRP3 inflammasome activity and the associated cascade reactions may be a promising approach for adjuvant treatment of epilepsy.…”

Section: Semaglutide Attenuates Seizure Severity and Ameliorates Cognitive Dysfunction By Blocking The Nlr Family Pyrin Domain Containingmentioning

confidence: 96%

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

et al. 2021

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Epilepsy comorbidities and anti-epileptic drugs (AEDs) are currently the main limitations of epilepsy treatment. Semaglutide is a glucagon like peptide-1 analogue that has entered the market as a new once-weekly drug for type II diabetes. The aim of the present study was to investigate the functions of semaglutide in epilepsy and inflammation models, in order to investigate its potential mechanism. In vitro, an inflammation model was established using lipopolysaccharide (LPS) and nigericin stimulation in BV2 cells. In vivo, chronic epilepsy model mice were generated using a pentylenetetrazole (PTZ) kindling method. BV2 cell proliferation was assessed using the Cell Counting Kit-8. The effects of semaglutide on NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and inflammatory cytokine secretion were determined using western blotting (WB) and ELISA. A lactate dehydrogenase (LDH) assay kit was used to detect the effect of semaglutide on LDH release. Electrocorticography and the modified Racine scale were used to assess seizure severity.Cognitive function was evaluated with behavioral assessment. Morphological changes in the hippocampus were observed with Nissl staining. Double immunofluorescence staining for NeuN and Iba-1, WB and immunofluorescence analysis of apoptosis-related proteins were used to evaluate neuronal apoptosis. The NLRP3 inflammasome was assessed by reverse transcription-quantitative PCR, WB and immunofluorescence staining, and inflammatory cytokine release was evaluated by WB analysis in the hippocampus of C57/BL6J model mouse. Semaglutide attenuated the LPS-and nigericin-induced inflammatory response and LDH release by blocking NLRP3 inflammasome activation in BV2 cells. Moreover, semaglutide decreased seizure severity, alleviated hippocampal neuronal apoptosis, ameliorated cognitive dysfunction, blocked NLRP3 inflammasome activation and decreased inflammatory cytokine secretion in PTZ-kindled mice. These results indicated that semaglutide reduced seizure severity, exerted neuroprotective effects and ameliorated cognitive dysfunction, possibly via inhibition of NLRP3 inflammasome activation and inflammatory cytokine secretion. Semaglutide may therefore be a novel, promising adjuvant therapeutic for epilepsy and its associated comorbidities.

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Section: Discussionmentioning

confidence: 97%

Section: Semaglutide Attenuates Seizure Severity and Ameliorates Cognitive Dysfunction By Blocking The Nlr Family Pyrin Domain Containingmentioning

confidence: 96%

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

et al. 2021

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“…Cyclooxygenase (COX) is a key enzyme that catalyzes arachidonic acid (AA) to produce various prostaglandins (PGs). There are mainly two types of isoenzymes, namely COX-1 and COX-2 [ 10 ]. COX-1 is mainly involved in normal vasodilatory and contractile functions, gastric mucosal protection, gastrointestinal blood flow regulation, and maintenance of normal renal function [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Parecoxib Sodium Preemptive Analgesia on the Recovery Period of General Anesthesia in Patients Undergoing Glioma Resection

Zhu

Guo

Tang³

et al. 2022

Journal of Oncology

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Objective. To investigate the effect of parecoxib sodium preemptive analgesia on postoperative complications and postoperative recovery of patients undergoing glioma resection. Methods. A total of 200 eligible patients with low-grade gliomas in the functional brain area scheduled for an awake craniotomy between January 2017 and December 2020 were reviewed. The subjects were divided into two groups: the study group (n = 100) given dexmedetomidine plus parecoxib sodium for pre-emptive analgesia 30 minutes preoperatively, and the control group (n = 100) receiving dexmedetomidine alone. Venous blood was collected before surgery, at the time of postoperative recovery, and 24 hours after operation, mean artery pressure (MAP) and heart rate (HR) were recorded during surgery. Sedation satisfaction, agitation rate, numerical pain score (NRS), postoperative complications, minimental state examination (MMSE) scores, quality of life (QoL) scores, and incidence of adverse events were also investigated after the surgery. Results. There were no significant differences in operation time, awakening time, intraoperative awakening time, and extubation time between the two groups ( P > 0.05 ). Compared with the control group, the ΔMAP (7.26 ± 2.21 versus 5.78 ± 2.36 mmHg) and the ΔHR (11.35 ± 3.66 versus 8.84 ± 2.47 beats/min) were significantly lower in the study group ( P < 0.05 ). Compared with the control group, the satisfaction was higher and agitation rate was lower in the study group ( P < 0.05 ). The incidence of intracranial infection and pulmonary infection decreased after operation ( P < 0.05 ). The NRS of the study group was remarkably lower than the control group at 12 hours postoperatively Preoperative MMSE score and QoL score showed no statistical difference ( P > 0.05 ), while postoperative MMSE and QoL scores showed statistical difference ( P < 0.05 ). Conclusion. This study suggests that parecoxib sodium can significantly improve the level of sedation and analgesia in patients undergoing glioma resection, reduce the incidence of intracranial infection and pulmonary infection.

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“…Experiments showed that the expressions of IL-18 were increased in the hippocampus of various epileptic models, but whether it is a protective or damaging factor remains controversial. [13][14][15] IL-18 binding protein (IL-18BP), being a readily secreted protein, belongs to shed soluble receptor category. With a high affinity for IL-18 (400 pM), IL-18BP can bind to IL-18 thus downregulating Th1 responses and reducing production of IFNγ.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Elevated serum free IL-18 in neuropsychiatric systemic lupus erythematosus patients with seizure disorders

Liang

Zheng

et al. 2022

Lupus

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Background Since dysregulation of total Interleukin (IL)-18 and IL-18 binding protein (IL-18BP) may participate in systemic lupus erythematosus (SLE) and contribute to the occurrence of non-autoimmune epilepsy, the aim of the current work is to investigate whether the interaction between IL-18 and IL-18BP plays any role in neuropsychiatric systemic lupus erythematosus related seizures. Methods Data from 137 SLE patients and 30 healthy controls (HC) were consecutively collected from 2020 to 2021. Serum levels of total IL-18 and IL-18BP for all patients and HC were measured by ELISA test. Free IL-18 was calculated based on the law of mass action. Results Among the 137 SLE patients, 103 had active disease and were classified into NPSLE ( n = 50) and Non-NPSLE ( n = 53) groups. Among the NPSLE patients, 16 had seizure disorders. Serum free IL-18 levels were increased in NPSLE (277.6 [150.9–428.8]pg/mL) and were correlated with disease activity (r = 0.268, p = 0.002). Moreover, serum free IL-18 levels in NPSLE patients with seizure disorders (350.9 [237.9–455.9]pg/mL) were significantly higher than the levels in those with other neuropsychiatric symptoms (237.7 [124.6–428.8] pg/mL). Conclusions The expression of free IL-18 was increased in neuropsychiatric systemic lupus erythematosus(NPSLE), especially in NPSLE related seizures. Also, serum levels of free IL-18 were significantly increased in active SLE patients. In this regard, free IL-18 may be involved in the pathogenesis of NPSLE related seizures and associated with disease activity.

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Ibuprofen Exerts Antiepileptic and Neuroprotective Effects in the Rat Model of Pentylenetetrazol-Induced Epilepsy via the COX-2/NLRP3/IL-18 Pathway

Cited by 39 publications

References 43 publications

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

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

Effect of Parecoxib Sodium Preemptive Analgesia on the Recovery Period of General Anesthesia in Patients Undergoing Glioma Resection

Elevated serum free IL-18 in neuropsychiatric systemic lupus erythematosus patients with seizure disorders

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