Inflammatory aspects of epileptogenesis: contribution of molecular inflammatory mechanisms

Alyu, Feyza; Dikmen, Miriş

doi:10.1017/neu.2016.47

Cited by 109 publications

(65 citation statements)

References 156 publications

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“…Finally, Diamond et al reported that an SNP in the interleukin‐1β ( IL‐1 β) gene is associated with increased risk of PTE, lower serum IL‐1β levels, and higher IL‐1β CSF/serum ratios. These data coincide with emerging evidence of a central role for IL‐1β signaling in ictogenesis and epileptogenesis …”

Section: Genetic Predisposition To Acquired Epilepsy In Humanssupporting

confidence: 86%

An animal model of genetic predisposition to develop acquired epileptogenesis: The FAST and SLOW rats

et al. 2019

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Epidemiological data and gene association studies suggest a genetic predisposition to developing epilepsy after an acquired brain insult, such as traumatic brain injury. An improved understanding of genetic determinants of vulnerability is imperative for early disease diagnosis and prognosis prediction, with flow‐on benefits for the development of targeted antiepileptogenic treatments as well as optimal clinical trial design. In the laboratory, one approach to investigate why some individuals are more vulnerable to acquired epilepsy than others is to examine unique rodent models exhibiting either vulnerability or resistance to epileptogenesis. This review focuses on the most well‐characterized of these models, the FAST (seizure‐prone) and SLOW (seizure‐resistant) rat strains, which were derived by selective breeding for differential amygdala electrical kindling rates. We describe how these strains differ in their seizure profiles, neuroanatomy, and neurobehavioral phenotypes, both at baseline and after a brain insult, with this knowledge proving fruitful to identify common pathological abnormalities associated with seizure susceptibility and psychiatric comorbidities. It is important to note that accruing data on strain differences in multiple biological processes provides insight into why some individuals may be more vulnerable to epileptogenesis, although future studies are evidently needed to identify the precise molecular and genetic risk factors. Together, the FAST and SLOW rat strains, and other similar experimental models, are invaluable neurobiological tools to investigate the effect of genetic background on acquired epilepsy risk, as well as the poorly understood relationship between epilepsy development and associated comorbidities.

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Section: Genetic Predisposition To Acquired Epilepsy In Humanssupporting

confidence: 86%

An animal model of genetic predisposition to develop acquired epileptogenesis: The FAST and SLOW rats

et al. 2019

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“…Independent samples t tests were performed. Scale bars: (A1-B3) 100 μm; inset 12.5 μm an increase in excitatory synaptic transmission [34], our findings suggest that M1/M2 phenotype determination could be modulated via MyD88, which may provide a target for supporting microenvironment maintenance in the hippocampus after SE.…”

Section: Discussionmentioning

confidence: 64%

Inhibition of MyD88 Signaling Skews Microglia/Macrophage Polarization and Attenuates Neuronal Apoptosis in the Hippocampus After Status Epilepticus in Mice

Liu

Zhang

et al. 2018

Neurotherapeutics

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Inflammation is implicated in epileptogenesis. Activated microglia and macrophages (MG/MΦ) are found in the brains of patients with epilepsy-related diseases and animal models of epilepsy. It is not yet known how the MG/MΦ activation phenotype affects pathological changes in the brain after a single seizure. In this study, we had 2 main purposes: first, to characterize poststatus epilepticus (SE) inflammation by tracking MG/MΦ polarization, and, second, to explore the role of an innate immune receptor adaptor protein, namely, myeloid differentiation primary response gene 88 (MyD88), in the induction of SE in a mouse model. A lithium-pilocarpine model of seizure conditions was generated in C57BL/6 mice. The intensity and distribution of MG/ MΦ polarization were tracked by fluorescent immunohistochemistry and Western blotting for the polarization markers inducible nitrogen oxygenized synthase, arginase-1, CD163, and mannose receptor. We observed steadily increasing M1 MG/MΦ along with MyD88 signal upregulation after SE in the hippocampi of mice, whereas the M2 marker arginase-1 was localized mainly in astrocytes rather than in MG/MΦ. Inhibition or gene knockout of MyD88 reduced M1 MG/MΦ and gliosis although increasing M2 MG/MΦ in the hippocampi of SE mice. MyD88 inhibition also augmented glutamate transporter 1 expression and reduced N-methyl-D-aspartate receptor NR1 subunit expression in the hippocampus to protect pyramidal neurons from apoptosis. These data suggest that MG/MΦ polarization after SE impacts the pathological outcome of the hippocampus via MyD88 signaling and point to MyD88 as a potential neuroprotective target for epilepsy therapy.

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“…As QAlb is influenced by many factors including body weight, sex, and seizures before CSF examination [24], this variable may have confounding effect. In addition, we speculate that other factors that are associated with BBB dysfunction but do not correlate with QAlb, such as inflammatory response elicited by seizures [25][26][27][28][29][30] and autoimmunity [31], also contribute to increased seizure frequency. Thus, it is necessary to evaluate other factors associated with chronic BBB dysfunction in patients with PEE.…”

Section: Discussionmentioning

confidence: 95%

Chronic dysfunction of blood-brain barrier in patients with post-encephalitic/encephalopathic epilepsy

Kimizu

Takahashi

Oboshi

et al. 2018

Seizure

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Keywords:Post-encephalitic/encephalopathic epilepsy Refractory epilepsy Blood-brain barrier dysfunction Albumin quotient A B S T R A C TPurpose: This study aimed to elucidate the characteristics and effects of chronic blood-brain barrier (BBB) dysfunction in patients with post-encephalitic/encephalopathic epilepsy (PEE), using brain images and the cerebral spinal fluid (CSF)/serum albumin ratio (albumin quotient, QAlb) as a marker of BBB function. Methods: We examined the albumin levels in CSF and serum samples from 312 patients with refractory epilepsy in our center between 2004 and 2015. Sixty samples from patients with PEE and 97 samples from age-and sexmatched disease controls (DC) were evaluated. We classified PEE patients into a widespread lesion group and a focal lesion group by severity on brain magnetic resonance images in the chronic phase after acute encephalitis/ encephalopathy. Results: Median QAlb was higher in PEE than in DC [median (range) ×10 3 : PEE 3.6 (1.0-10.3) versus DC 2.7 (1.0-6.7), p = 0.007]. In a linear regression analysis of the relationship between QAlb and patient's age at CSF examination or duration of epilepsy, the slope of the regression line was greater in PEE than in DC. Furthermore, in patients under ten years of age, linear regression analysis of QAlb versus seizure frequency showed a weak but positive correlation. Among PEE patients, seizure frequency was higher in the widespread lesion group than in the focal lesion group [300 (4-3000) versus 30 (1-1500) seizures/month, p < 0.001]. Conclusion: Our study suggests that patients with PEE have more severe BBB dysfunction, and that the BBB dysfunction is associated with refractory epilepsy.In this retrospective study, we examined the albumin levels in CSF

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Inflammatory aspects of epileptogenesis: contribution of molecular inflammatory mechanisms

Abstract: The literature research indicated that inflammation is a part of epileptogenesis. For this reason, further studies are necessary for assessing agents that will be effective in clinical use for therapeutic treatment of epileptogenesis.

Cited by 109 publications

References 156 publications

An animal model of genetic predisposition to develop acquired epileptogenesis: The FAST and SLOW rats

An animal model of genetic predisposition to develop acquired epileptogenesis: The FAST and SLOW rats

Inhibition of MyD88 Signaling Skews Microglia/Macrophage Polarization and Attenuates Neuronal Apoptosis in the Hippocampus After Status Epilepticus in Mice

Chronic dysfunction of blood-brain barrier in patients with post-encephalitic/encephalopathic epilepsy

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