Meta-analysis of HMGB1 levels in the cerebrospinal fluid and serum of patients with epilepsy

Chen, Yue; Chen, Xilu; Liu, Ying

doi:10.1007/s10072-023-06720-0

Cited by 8 publications

(2 citation statements)

References 41 publications

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“…Furthermore, we tested for statistical heterogeneity using the I 2 statistic. If no heterogeneity exists between the results of the studies ( p > 0.1, I 2 ≤ 50%), then we used a fixed-effects model in the meta-analysis with the corresponding outcome indicators ( Chen et al, 2023 ). Meanwhile, if heterogeneity existed between the results of the studies, then we used a random-effects model in the meta-analysis.…”

Section: Methodsmentioning

confidence: 99%

Meta-analysis of MMP-9 levels in the serum of patients with epilepsy

Wang,

Lin,

Yao

et al. 2024

Front. Neurosci.

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BackgroundEpilepsy’s pathogenesis and progression are significantly influenced by neuroinflammation, blood–brain barrier function, and synaptic remodeling function. Matrix metalloproteinase 9 (MMP-9), as a critical factor, may contribute to the development of epilepsy through one or more of the above-mentioned pathways. This study aims to evaluate and quantify the correlation between MMP-9 levels and epilepsy.MethodsWe conducted a comprehensive search of Embase, Web of Science, PubMed, Cochrane Library, WanFang DATA, VIP, and the CNKI to identify studies that investigate the potential association between MMP-9 and epilepsy. The data were independently extracted by two researchers and assessed for quality using the Cochrane Collaboration tool. The extracted data were analyzed using Stata 15 and Review Manager 5.4. The study protocol was registered prospectively at PROSPERO, ID: CRD42023468493.ResultsThirteen studies with a total of 756 patients and 611 matched controls met the inclusion criteria. Eight of these studies reported total serum MMP-9 levels, and the other five studies were used for a further subgroup analysis. The meta-analysis indicated that the serum MMP-9 level was higher in epilepsy patients (SMD = 4.18, 95% confidence interval = 2.18–6.17, p < 0.00001) compared with that in the control group. Publication bias was not detected according to Begg’s test. The subgroup analysis of country indicated that the epilepsy patients in China, Poland, and Egypt had higher levels of serum MMP-9 than the control group, with the increase being more pronounced in Egypt. The subgroup analysis of the age category demonstrated that the serum MMP-9 levels of the adult patients with epilepsy were significantly higher than those of the matched controls. However, the serum MMP-9 levels did not significantly differ in children with epilepsy. The subgroup analysis of the seizure types demonstrated substantial difference in the MMP-9 levels between patients of seizure-free epilepsy (patients who have been seizure-free for at least 7 days) and the control group. Meanwhile, the serum MMP-9 level in patients with epileptic seizures was significantly higher than that in the control group. The subgroup analysis based on seizure duration in patients showed that the serum MMP-9 levels at 1–3, 24, and 72 h after seizure did not exhibit significant differences between female and male patients with epilepsy when compared with the control group. The serum MMP-9 levels at 1–3 and 24 h were significantly higher than those of the matched controls. Nevertheless, the serum MMP-9 level at 72 h was not significantly different from that in the control group.ConclusionThis meta-analysis presents the first comprehensive summary of the connection between serum MMP-9 level and epilepsy. The MMP-9 levels in epilepsy patients are elevated. Large-scale studies with a high level of evidence are necessary to determine the exact relationship between MMP-9 and epilepsy.

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Section: Methodsmentioning

confidence: 99%

Meta-analysis of MMP-9 levels in the serum of patients with epilepsy

Wang,

Lin,

Yao

et al. 2024

Front. Neurosci.

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“…Effects of NRICM on the protein levels of HMGB1 and TLR4 in the cortex and hippocampus HMGB1 is a ubiquitous protein that has been reported to be increased in the serum and brain tissue of patients with epilepsy and in the brain tissue in of epilepsy model animal; moreover, HMGB1 promotes the synthesis of in ammatory cytokines by activating TLR4, thereby in uencing in ammatory responses (Fig. 8A) (Kaya et al, 2021;Chen et al, 2023;Yue et al, 2023). We observed substantial neuronal damage in the cortex and hippocampus after KA-induced seizures that was concomitant with an increase in the number of activated astrocytes and the expression of in ammatory cytokines.…”

Section: Effects Of Nricm101 On the Protein Levels Of Il-1β Il-1r1 Il...mentioning

confidence: 99%

Taiwan Chingguan Yihau (NRICM101) prevents kainic acid-induced seizures in rats by modulating neuroinflammation and the glutamatergic system

Hung,

Chiu,

Chen

et al. 2024

Preprint

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Taiwan Chingguan Yihau (NRICM101) is a Traditional Chinese medicine (TCM) formula used to treat coronavirus disease 2019; however, its impact on epilepsy has not been revealed. Therefore, the present study evaluated the anti-epileptogenic effect of orally administered NRICM101 on kainic acid (KA)-induced seizures in rats and investigated its possible mechanisms of action. Sprague‒Dawley rats were administered NRICM101 (300 mg/kg) by oral gavage for 7 consecutive days before receiving an intraperitoneal injection of KA (15 mg/kg). NRICM101 considerably reduced the seizure behavior and electroencephalographic seizures induced by KA in rats. NRICM101 also significantly decreased the neuronal loss and glutamate increase and increased GLAST, GLT-1, GAD67, GDH and GS levels in the cortex and hippocampus of KA-treated rats. In addition, NRICM101 significantly suppressed astrogliosis (as determined by decreased GFAP expression); neuroinflammatory signaling (as determined by reduced HMGB1, TLR-4, IL-1β, IL-1R, IL-6, p-JAK2, p-STAT3, TNF-α, TNFR1 and p-IκB levels, and increased cytosolic p65-NFκB levels); and necroptosis (as determined by decreased p-RIPK3 and p-MLKL levels) in the cortex and hippocampus of KA-treated rats. The effects of NRICM101 were similar to those of carbamazepine, a well-recognized antiseizure drug. Furthermore, no toxic effects of NRICM101 on the liver and kidney were observed in NRICM101-treated rats. The results indicate that NRICM101 has antiepileptogenic and neuroprotective effects through the suppression of the inflammatory cues (HMGB1/TLR4, Il-1β/IL-1R1, IL-6/p-JAK2/p-STAT3, and TNF-α/TNFR1/NF-κB) and necroptosis signaling pathways (TNF-α/TNFR1/RIP3/MLKL) associated with glutamate level regulation in the brain and is innocuous. Our findings highlight the promising role of NRICM101 in the management of epilepsy.

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Research progress on the role of inflammatory mediators in the pathogenesis of epilepsy

Yu,

Sun

2024

Ibrain

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Epilepsy is an abnormal neurologic disorder distinguished by the recurrent manifestation of seizures, and the precise underlying mechanisms for its development and progression remain uncertain. In recent years, the hypothesis that inflammatory mediators and corresponding pathways contribute to seizures has been supported by experimental results. The potential involvement of neuroinflammation in the development of epilepsy has garnered growing interest. This review centers attention on the involvement of inflammatory mediators in the emergence and progression of epilepsy within recent years, focusing on both clinical research and animal models, to enhance comprehension of the intricate interplay between brain inflammation and epileptogenesis.

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Meta-analysis of HMGB1 levels in the cerebrospinal fluid and serum of patients with epilepsy

Cited by 8 publications

References 41 publications

Meta-analysis of MMP-9 levels in the serum of patients with epilepsy

Meta-analysis of MMP-9 levels in the serum of patients with epilepsy

Taiwan Chingguan Yihau (NRICM101) prevents kainic acid-induced seizures in rats by modulating neuroinflammation and the glutamatergic system

Research progress on the role of inflammatory mediators in the pathogenesis of epilepsy

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