Cytokine-chemokine profiles in the hippocampus of patients with mesial temporal lobe epilepsy and hippocampal sclerosis

Aulická, Štefánia; Česká, Katarína; Šána, Jiří; Siegl, František; Brichtová, Eva; Ošlejšková, Hana; Hermanová, Markéta; Hendrych, Michal; Michu, Elleni; Brázdil, Milan; Slabý, Ondřej; Nestrašil, Igor

doi:10.1016/j.eplepsyres.2022.106858

“…Reduced frequency of IFN-γ, TNF-α, IL-17, and IL-4 in CD8+ T lymphocytes of TLE+HS patients was observed ( Rosa et al, 2016 ). Note that the occurrence of febrile seizures did not affect the expression of cytokines and chemokines in TLE+HS patients ( Aulická et al, 2022 ).…”

Section: Discussionmentioning

confidence: 97%

Integrated Analysis of Expression Profile and Potential Pathogenic Mechanism of Temporal Lobe Epilepsy With Hippocampal Sclerosis

Wang

¹

,

Qu

²

,

Yang

³

et al. 2022

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ObjectiveTo investigate the potential pathogenic mechanism of temporal lobe epilepsy with hippocampal sclerosis (TLE+HS) by analyzing the expression profiles of microRNA/ mRNA/ lncRNA/ DNA methylation in brain tissues.MethodsBrain tissues of six patients with TLE+HS and nine of normal temporal or parietal cortices (NTP) of patients undergoing internal decompression for traumatic brain injury (TBI) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60K. The cDNA was labeled and hybridized to the Agilent LncRNA+mRNA Human Gene Expression Microarray V3.0,4 × 180K. For methylation detection, the DNA was labeled and hybridized to the Illumina 450K Infinium Methylation BeadChip. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value < 0.05 and absolute fold change >2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor. BrainSpan database was used to screen for signatures that were not differentially expressed in normal human hippocampus and cortex (data from BrainSpan), but differentially expressed in TLE+HS’ hippocampus and NTP’ cortex (data from our cohort). The strategy “Guilt by association” was used to predict the prospective roles of each important hub mRNA, miRNA, or lncRNA.ResultsA significantly negative correlation (r < −0.5) was found between 116 pairs of microRNA/mRNA, differentially expressed in six patients with TLE+HS and nine of NTP. We examined this regulation network’s intersection with target gene prediction results and built a lncRNA-microRNA-Gene regulatory network with structural, and functional significance. Meanwhile, we found that the disorder of FGFR3, hsa-miR-486-5p, and lnc-KCNH5-1 plays a key vital role in developing TLE+HS.

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“…A significantly higher IL-6/IL-10 ratio in TLE+HS may reflect the dysregulation in proinflammatory and antiinflammatory cytokine balance, a possible pathophysiological mechanism contributing to neuroinflammation in DRE [31]. Most TLE-associated HS studies on cytokines, particularly IL-6 and IL-10, are performed in HS tissue samples rather than in body fluids, plasma, or serum samples, providing inconsistent results [32][33][34][35]. A recent study found an upregulated RNA tissue expression of several immune mediators such as IL-1β, IL-18, CCL2, CCL3, and CCL4 in TLE with HS patients when compared to the postmortem hippocampal samples collected from autopsy controls suggesting their role in the neuroinflammatory process contributing to mesial TLE epileptogenesis [32].…”

Section: Discussionmentioning

confidence: 99%

“…Most TLE-associated HS studies on cytokines, particularly IL-6 and IL-10, are performed in HS tissue samples rather than in body fluids, plasma, or serum samples, providing inconsistent results [32][33][34][35]. A recent study found an upregulated RNA tissue expression of several immune mediators such as IL-1β, IL-18, CCL2, CCL3, and CCL4 in TLE with HS patients when compared to the postmortem hippocampal samples collected from autopsy controls suggesting their role in the neuroinflammatory process contributing to mesial TLE epileptogenesis [32]. However, it is interesting that the authors did not find detectable expression of IL-6 either in the TLE patients with HS or in the autopsy controls [32].…”

Section: Discussionmentioning

confidence: 99%

The Regulation of Plasma Interleukin-6 Levels Is Modified by Hippocampal Sclerosis and Its Lateralization in Drug-Resistant Temporal Lobe Epilepsy

Peltola

¹

,

Basnyat

²

,

Liimatainen

³

et al. 2023

Acta Neurologica Scandinavica

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Background. Several studies have reported the association of the proinflammatory cytokine IL-6 with temporal lobe epilepsy (TLE), but the regulation of IL-6 in hippocampal sclerosis (HS) is less studied. Objectives. To analyse IL-6 levels and the IL-6/IL-10 ratio in a larger, well-characterized group of patients with drug-resistant focal epilepsy (DRE), focusing especially on TLE and TLE-associated HS. Methods. IL-6 levels were measured by ELISA in plasma in a cross-sectional cohort of 265 patients comprising TLE with HS ( n = 34 ), TLE without HS ( n = 103 ), extratemporal lobe epilepsy ( n = 92 ), and idiopathic generalized epilepsy ( n = 36 ). Results. The IL-6/IL-10 ratio was higher in TLE with HS than in TLE without HS (3.1 vs. 1.6, p = 0.042 ), whereas the median levels of IL-6 did not differ among epilepsy types. TLE without HS patients had a higher proportion of increased IL-6 levels than TLE with HS patients ( p = 0.021 ). Additionally, IL-6 levels were higher in patients with right-sided HS than in those with left lateralization (1.71 vs. 0.80 pg/mL, p = 0.04 ). In TLE with HS patients, IL-6 levels showed a negative correlation with seizure frequency during the last month ( r = − 0.342 ; p = 0.047 ), whereas in TLE without HS patients, the correlation was positive but did not reach significance ( r = 0.136 ; p = 0.169 ). Conclusion. IL-6 levels and the IL-6/IL-10 ratio are differentially regulated among patients with TLE depending on the presence of HS and its lateralization, suggesting that TLE with HS is a distinct category regarding cytokine activation.

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“…Consistent with our results, a few studies have shown that in patients with neuroinflammatory diseases, the serum and liquor samples of CCL11 levels were higher, including in neuromyelitis optica spectrum disorders [ 48 ]. More interestingly, in the study of the correlation of certain chemokines and cytokines’ expression in the brain, the different anatomical regions showed epilepsy-related eotaxin differences [ 19 ]. In particular, the perivascular astrocytes secrete CCL11; next, in response to this, the microglial cells upregulate the expression of the receptors CCR2, CCR3 and CCR5, acting as receptors for CCL11, especially in the hippocampus compared to the entorhinal and temporal cortices.…”

Section: Discussionmentioning

confidence: 99%

“…These control leukocyte migration and have a possible role in neuromodulation [ 18 ]. It has been demonstrated that some chemokine–receptor pairs, including CCL2, CCL3, CCL4 and CCL11, are highly expressed in hippocampal tissues and have been associated with epilepsy, based on the findings of experimental models of epilepsy and immunohistochemistry of brain tissue samples from patients undergoing surgical treatment for refractory seizures [ 19 ]. The stimulation of these receptors can facilitate the release of excitatory neurotransmitters, including glutamate, causing secondary neurotoxicity and nerve cell death [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Alterations of Plasma Pro-Inflammatory Cytokine Levels in Children with Refractory Epilepsies

Gakharia

¹

,

Bakhtadze

²

,

Lim

³

et al. 2022

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Paediatric epilepsy is a multifaceted neurological disorder with various aetiologies. Up to 30% of patients are considered drug-resistant. The background impact of interfering inflammatory and neuronal pathways has been closely linked to paediatric epilepsy. The characteristics of the inflamed state have been described not only in epilepsies, which are considered prototypes of an inflammatory pathophysiology, but also in patients with drug-resistant epilepsy, especially in epileptic encephalopathies. The imbalance of different cytokine levels was confirmed in several epileptic models. Chemokines are new targets for exploring neuroimmune communication in epileptogenesis, which control leukocyte migration and have a possible role in neuromodulation. Additionally, prostaglandin E2 (PGE2) is an important effector molecule for central neural inflammatory responses and may influence drug responsiveness. We measured the serum interictal quantitative levels of chemokines (CCL2, CCL4, CCL11) and PGE2 in correlation with the seizure frequency and severity in controlled and intractable childhood epilepsies. Our refractory seizure group demonstrated significantly increased concentrations of eotaxin (CCL11) compared to the controlled epilepsy group. The higher level of CCL11 was correlated with an increased seizure frequency, while the PGE2 levels were associated with the severity of seizure and epilepsy, supporting the findings that proinflammatory cytokines may contribute to epileptogenesis and possibly have a role in developing seizure resistance.

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Cytokine-chemokine profiles in the hippocampus of patients with mesial temporal lobe epilepsy and hippocampal sclerosis

Cited by 15 publications

References 35 publications

Integrated Analysis of Expression Profile and Potential Pathogenic Mechanism of Temporal Lobe Epilepsy With Hippocampal Sclerosis

Integrated Analysis of Expression Profile and Potential Pathogenic Mechanism of Temporal Lobe Epilepsy With Hippocampal Sclerosis

The Regulation of Plasma Interleukin-6 Levels Is Modified by Hippocampal Sclerosis and Its Lateralization in Drug-Resistant Temporal Lobe Epilepsy

Alterations of Plasma Pro-Inflammatory Cytokine Levels in Children with Refractory Epilepsies

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