The Effects of Levetiracetam on Cerebrospinal Fluid and Plasma NPY and GAL, and on the Components of Stress Response System, hs-CRP, and S100B Protein in Serum of Patients with Refractory Epilepsy

Chen, Wenzhen; Tan, Yan; Ge, Yu-Xing; Chen, Yujuan; Liu, Xueyuan

doi:10.1007/s12013-015-0683-8

Cited by 18 publications

(9 citation statements)

References 44 publications

(48 reference statements)

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“…Twenty-two records were identified for full-text analysis. We scrutinized these records and excluded four due to a lack of necessary data (Yelmo et al, 2012; Chen et al, 2015), because the results were also reported in other publications (Lu, 2010; Chen, 2011a). Ultimately, 18 studies encompassing 1,057 cases and 821 controls met the criteria for inclusion in our meta-analysis (Figure 1) (Portela et al, 2003; Li et al, 2004; Yun, 2009; Lu et al, 2010; Chen, 2011b; Liu et al, 2011; Atici et al, 2012; Mikkonen et al, 2012; Shiihara et al, 2012; Wang and Han, 2012; Xu et al, 2012; Yuan et al, 2014; Yun et al, 2015; Wang et al, 2016, 2018; Hao et al, 2017; Zhao et al, 2017; Zhang et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

Increased Serum S100B Levels in Patients With Epilepsy: A Systematic Review and Meta-Analysis Study

Liang

Liu³

et al. 2019

Front. Neurosci.

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Importance: Accumulating evidence suggests that serum levels of S100B may play a role in epilepsy. Objective: We performed a meta-analysis to quantitatively summarize the serum S100B data available for patients with epilepsy. Data source: Two independent researchers conducted a systematic investigation of the Harvard Hollis+, Open Gray, Clinicaltrials, Wanfangdata, and CNKI databases through Dec 6, 2018, for all studies published in English and Chinese. The search terms included S100B and calcium-binding protein B in combination with epilepsy. Study selection: Original studies and reported data from these search terms are included. Studies where data overlapped with other studies were excluded. Data extraction and synthesis: investigators extracted, pooled and analyzed data from the included studies using a fixed-effects model in the Comprehensive Meta-Analysis3.3 and R software. Main outcomes and measures: Peripheral blood levels of S100B in patients with epilepsy compared with controls. Aberrations in peripheral blood levels of S100B were hypothesized to be related to epilepsy. Results: a fixed-effects meta-analysis of all 18 studies, including 1,057 unique participants, indicated that patients with epilepsy had significantly increased peripheral blood levels of S100B compared to controls (Hedges g = 1.568, 95% CI =1.431–1.706, P < 0.001). Sensitivity analysis showed that no single study significantly influenced the overall association of peripheral blood levels of S100B and epilepsy. Most of the subgroup analyses, including those of country, assay type and publication language, demonstrated a statistically significant association between peripheral blood levels of S100B and epilepsy. Meta-regression analyses indicated that gender (regression coefficient [SE], −0.2524 [0.0641]; 95%CI, −0.3781 to −0.1267; P = 0.0001) and mean age (regression coefficient [SE], −0.1224 [0.0426]; 95% CI, −0.2058 to −0.0390; P = 0.0040) might present serum S100B reductions, but sample size, years, assay type, publication language and country did not show moderating effects on the effect sizes. Furthermore, the trim-and-fill method used to adjust for funnel plot asymmetry in our meta-analysis confirmed that a positive outcome is unlikely to be due to publication bias. Conclusion and relevance: the results of this meta-analysis provide evidence for a significant increase in serum S100B levels in patients with epilepsy. Serum S100B is the most worthwhile biomarker of epilepsy, which is helpful for the clinical diagnosis and prognosis of epilepsy.

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Section: Resultsmentioning

confidence: 99%

Increased Serum S100B Levels in Patients With Epilepsy: A Systematic Review and Meta-Analysis Study

Liang

Liu³

et al. 2019

Front. Neurosci.

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“…Hence, it prohibits the induction of inflammatory response. Chen et al . report the decreasing serum activity of PON1 in levetiracetam treatment compared with control.…”

Section: Discussionmentioning

confidence: 99%

Antiepileptic drugs: Impacts on human serum paraoxonase‐1

Beydemır

Demir

2016

J Biochem & Molecular Tox

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Serum paraoxonase (PON1) is a key enzyme related to high-density lipoprotein (HDL)-cholesterol particle. It can prevent the oxidation of low-density lipoprotein (LDL) and HDL. The present article focuses on the in vitro inhibition role of some antiepileptic drugs (AEDs) such as valproic acid, gabapentin, primidone, phenytoin, and levetiracetam on human paraoxonase (hPON1). Therefore, PON1 was purified from human serum with a specific activity of 3976.36 EU/mg and 13.96% yield by using simple chromatographic methods. The AEDs were tested at various concentrations, which showed reduced in vitro hPON1 activity. IC values for gabapentin, valproic acid, primidone, phenytoin, and levetiracetam were found to be 0.35, 0.67, 0.87, 6.3, and 53.3 mM, respectively. K constants were 0.261 ± 0.027, 0.338 ± 0.313, 0.410 ± 0.184, 10.3 ± 0.001, and 43.01 ± 0.003 mM, respectively. Gabapentin exhibited effective inhibitory activity as compared with the other drugs. The inhibition mechanisms of all compounds were noncompetitive.

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“…As previously mentioned, S100B is widely used as a marker for epileptic disorders [ 31 , 32 ], and its secretion is modulated by anti-inflammatory drugs [ 35 , 36 ]. Our studies have suggested that the hippocampal and CSF S100B are altered after SE induction in the Li-pilocarpine model [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…The S100B protein is a glial protein that is a widely used marker for brain injury conditions, including epileptic disorders [ 31 , 32 ], and indeed displays an augmented secretion during brain injury condition, working as a neurotrophic cytokine or simply as a damage-associated molecular pattern (DAMP) [ 33 ]. Moreover, S100B secretion is modulated by LPS [ 34 ] and anti-inflammatory drugs [ 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of dexamethasone on the Li-pilocarpine model of epilepsy: protection against hippocampal inflammation and astrogliosis

Vizuete

Hansen

Negri

et al. 2018

J Neuroinflammation

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BackgroundTemporal lobe epilepsy (TLE) is the most common form of partial epilepsy and is accompanied, in one third of cases, by resistance to antiepileptic drugs (AED). Most AED target neuronal activity modulated by ionic channels, and the steroid sensitivity of these channels has supported the use of corticosteroids as adjunctives to AED. Assuming the importance of astrocytes in neuronal activity, we investigated inflammatory and astroglial markers in the hippocampus, a key structure affected in TLE and in the Li-pilocarpine model of epilepsy.MethodsInitially, hippocampal slices were obtained from sham rats and rats subjected to the Li-pilocarpine model of epilepsy, at 1, 14, and 56 days after status epilepticus (SE), which correspond to the acute, silent, and chronic phases. Dexamethasone was added to the incubation medium to evaluate the secretion of S100B, an astrocyte-derived protein widely used as a marker of brain injury. In the second set of experiments, we evaluated the in vivo effect of dexamethasone, administrated at 2 days after SE, on hippocampal inflammatory (COX-1/2, PGE2, and cytokines) and astroglial parameters: GFAP, S100B, glutamine synthetase (GS) and water (AQP-4), and K+ (Kir 4.1) channels.ResultsBasal S100B secretion and S100B secretion in high-K+ medium did not differ at 1, 14, and 56 days for the hippocampal slices from epileptic rats, in contrast to sham animal slices, where high-K+ medium decreased S100B secretion. Dexamethasone addition to the incubation medium per se induced a decrease in S100B secretion in sham and epileptic rats (1 and 56 days after SE induction). Following in vivo dexamethasone administration, inflammatory improvements were observed, astrogliosis was prevented (based on GFAP and S100B content), and astroglial dysfunction was partially abrogated (based on Kir 4.1 protein and GSH content). The GS decrease was not prevented by dexamethasone, and AQP-4 was not altered in this epileptic model.ConclusionsChanges in astroglial parameters emphasize the importance of these cells for understanding alterations and mechanisms of epileptic disorders in this model. In vivo dexamethasone administration prevented most of the parameters analyzed, reinforcing the importance of anti-inflammatory steroid therapy in the Li-pilocarpine model and possibly in other epileptic conditions in which neuroinflammation is present.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1109-5) contains supplementary material, which is available to authorized users.

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The Effects of Levetiracetam on Cerebrospinal Fluid and Plasma NPY and GAL, and on the Components of Stress Response System, hs-CRP, and S100B Protein in Serum of Patients with Refractory Epilepsy

Cited by 18 publications

References 44 publications

Increased Serum S100B Levels in Patients With Epilepsy: A Systematic Review and Meta-Analysis Study

Increased Serum S100B Levels in Patients With Epilepsy: A Systematic Review and Meta-Analysis Study

Antiepileptic drugs: Impacts on human serum paraoxonase‐1

Effects of dexamethasone on the Li-pilocarpine model of epilepsy: protection against hippocampal inflammation and astrogliosis

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