Brain expression of inflammatory mediators in Mesial Temporal Lobe Epilepsy patients

Leal, Bárbara; Chaves, João; Carvalho, Cláudia; Rangel, Rui; Santos, Agostinho; Bettencourt, Andreia; Lopes, João; Ramalheira, João; Silva, Ana Martins; Silva, António Martins da; Costa, Paulo

doi:10.1016/j.jneuroim.2017.10.014

Cited by 54 publications

(43 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…patients with different seizure types reflected the severity of epilepsy (16)(17)(18). Dubé et al found that inflammatory cytokines (such as IL-1β) played a crucial role in epilepsy caused by febrile seizures in children (19).…”

Section: Figure 4 |mentioning

confidence: 99%

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

Zhang

Chen

et al. 2020

Front. Neurol.

View full text Add to dashboard Cite

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.

show abstract

Section: Figure 4 |mentioning

confidence: 99%

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

Zhang

Chen

et al. 2020

Front. Neurol.

View full text Add to dashboard Cite

show abstract

“…Experimental data from rodent models confirmed that enhanced activation of inflammatory pathways can contribute to enhanced excitability and lowered thresholds in the epileptic brain [3][4][5]. Moreover, increased expression rates of various pro-inflammatory mediators have been demonstrated in brain tissue from rodent epilepsy models as well as human patients with epilepsy [1,[6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 78%

Molecular alterations of the TLR4-signaling cascade in canine epilepsy

et al. 2020

View full text Add to dashboard Cite

Background: Cumulating evidence from rodent models points to a pathophysiological role of inflammatory signaling in the epileptic brain with Toll-like receptor-4 signaling acting as one key factor. However, there is an apparent lack of information about expression alterations affecting this pathway in canine patients with epilepsy. Therefore, we have analyzed the expression pattern of Toll-like receptor 4 and its ligands in brain tissue of canine patients with structural or idiopathic epilepsy in comparison with tissue from laboratory dogs or from owner-kept dogs without neurological diseases. Results: The analysis revealed an overexpression of Toll-like receptor-4 in the CA3 region of dogs with structural epilepsy. Further analysis provided evidence for an upregulation of Toll-like receptor-4 ligands with high mobility group box-1 exhibiting increased expression levels in the CA1 region of dogs with idiopathic and structural epilepsy, and heat shock protein 70 exhibiting increased expression levels in the piriform lobe of dogs with idiopathic epilepsy. In further brain regions, receptor and ligand expression rates proved to be either in the control range or reduced below control levels. Conclusions: Our study reveals complex molecular alterations affecting the Toll-like receptor signaling cascade, which differ between epilepsy types and between brain regions. Taken together, the data indicate that multitargeting approaches modulating Toll-like receptor-4 signaling might be of interest for management of canine epilepsy. Further studies are recommended to explore respective molecular alterations in more detail in dogs with different etiologies and to confirm the role of the pro-inflammatory signaling cascade as a putative target.

show abstract

“…Gliosis is a remarkable characteristic of HS. The distribution and profile of reactive astrocytes depend on HS type, and also on localization and severity of neuronal loss and inflammatory mediators in human TLE and experimental models . Activated microglia seem to play a major role in this regard, keeping the astrocytes in reactive status .…”

Section: Discussionmentioning

confidence: 99%

“…It is possible that continuous central nervous system cells activation, especially glia, can lead to apoptosis in TLE hippocampi by overexpression of pro‐inflammatory cytokines and chemokines, which induce DNA and mitochondrial damage, and by direct upregulation of apoptotic proteins of the Bcl‐2 family …”

Section: Discussionmentioning

confidence: 99%

“…In TLE‐associated HS, astrogliosis exhibits moderate to severe (fibrillary) distribution in CA subfields and is co‐localized with neuronal loss in histopathological analyses . HS is also associated with microglial activation and increased expression of cytokines such as interleukin‐beta (IL)‐1β in hippocampi from patients with TLE . Importantly, a neuroinflammatory milieu contributes to hyperexcitability, decreasing gamma‐aminobutyric acid currents, increasing cellular influx of calcium ions and neurotransmitters efflux, among other effects .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bcl‐2/Bax ratio increase does not prevent apoptosis of glia and granular neurons in patients with temporal lobe epilepsy

et al. 2019

View full text Add to dashboard Cite

Temporal lobe epilepsy (TLE) is usually associated with hippocampal sclerosis (HS), characterized by gliosis and neuronal loss, mainly in the cornus ammonis (CA). Regardless the type of HS, gliosis is associated with neuronal loss. Indeed, glial reactivation seems to induce both neuronal and glial apoptosis. Anti‐apoptotic mechanisms are also activated in order to contain the cell death in chronic epilepsy. However, the role of the intrinsic apoptosis pathway in human TLE is unclear, mainly in relation to glial death. The purpose of this study was to evaluate the reactive gliosis areas in parallel with Bcl‐2/Bax ratio and active caspase 3 immunoreactivity in hippocampi of TLE patients in comparison with control hippocampi. We also sought to investigate whether the levels of these markers were correlated with TLE clinical parameters. Paraffin‐embedded sclerotic and control hippocampi were collected for immunohistochemical analyses of glial fibrillary acidic protein (GFAP), human leucocyte antigen DR (HLA‐DR), neuronal nuclei protein (NeuN), Bax, Bcl‐2 and active caspase 3. Sclerotic hippocampi presented higher immunoreactivity areas of GFAP and HLA‐DR than controls, with similar values in HS types 1 and 2. Bcl‐2 protein expression was increased in epileptic hippocampi, while Bax expression was similar to controls. Despite Bcl2/Bax ratio increase, granular neurons and glia exhibited active caspase 3 expression in TLE hippocampi, while controls did not show staining for the same marker. In conclusion, glial and neuronal death is increased in sclerotic hippocampi, independently of HS type, and co‐localized with gliosis. Furthermore, Bcl‐2/Bax ratio increase does not prevent expression of active caspase 3 by glia and granular neurons in TLE.

show abstract

Brain expression of inflammatory mediators in Mesial Temporal Lobe Epilepsy patients

Cited by 54 publications

References 87 publications

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

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

Molecular alterations of the TLR4-signaling cascade in canine epilepsy

Bcl‐2/Bax ratio increase does not prevent apoptosis of glia and granular neurons in patients with temporal lobe epilepsy

Contact Info

Product

Resources

About