Why mesial temporal lobe epilepsy with hippocampal sclerosis is progressive: Uncontrolled inflammation drives disease progression?

Yang, Tianhua; Zhou, Dong; Stefan, Hermann

doi:10.1016/j.jns.2010.06.002

Cited by 69 publications

(66 citation statements)

References 97 publications

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“…Recent studies have highlighted that self-propagating seizure activities in TLE may result in dysregulated inflammation, blood brain barrier damage and neuronal damage [24]. Since HSP70, S100ßP, NSE, as well as plasma nuclear and mitochondrial DNA levels have been shown to reflect central nervous system damage, the present study hypothesized that these biomarkers may be of prognostic value in TLE patients from the cognitive aspect.…”

Section: Introductionmentioning

confidence: 85%

Clinical significance of serological biomarkers and neuropsychological performances in patients with temporal lobe epilepsy

et al. 2012

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BackgroundTemporal lobe epilepsy (TLE) is a common form of focal epilepsy. Serum biomarkers to predict cognitive performance in TLE patients without psychiatric comorbidities and the link with gray matter (GM) atrophy have not been fully explored.MethodsThirty-four patients with TLE and 34 sex - and age-matched controls were enrolled for standardized cognitive tests, neuroimaging studies as well as measurements of serum levels of heat shock protein 70 (HSP70), S100ß protein (S100ßP), neuronal specific enolase (NSE), plasma nuclear and mitochondrial DNA levels.ResultsCompared with the controls, the patients with TLE had poorer cognitive performances and higher HSP70 and S100ßP levels (p < 0.01). The patients with higher frequencies of seizures had higher levels of HSP70, NSE and S100ßP (p < 0.01). Serum HSP70 level correlated positively with duration of epilepsy (σ = 0.413, p < 0.01), and inversely with memory scores in the late registration (σ = −0.276, p = 0.01) and early recall score (σ = −0.304, p = 0.007). Compared with the controls, gray matter atrophy in the hippocampal and parahippocampal areas, putamen, thalamus and supplementary motor areas were found in the patient group. The HSP70 levels showed an inverse correlation with hippocampal volume (R square = 0.22, p = 0.007) after controlling for the effect of age.ConclusionsOur results suggest that serum biomarkers were predictive of higher frequencies of seizures in the TLE group. HSP70 may be considered to be a stress biomarker in patients with TLE in that it correlated inversely with memory scores and hippocampal volume. In addition, the symmetric extratemporal atrophic patterns may be related to damage of neuronal networks and epileptogenesis in TLE.

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Section: Introductionmentioning

confidence: 85%

Clinical significance of serological biomarkers and neuropsychological performances in patients with temporal lobe epilepsy

et al. 2012

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“…In this way microglia can be recruited to sites of injury, where they can respond by ameliorating the damage [3,4]. However, there have also been numerous reports of detrimental microglial activity in response to injury, and neuroinflammation is thought to play a major role in pathogenesis of many neurological disorders, including epilepsy and Alzheimer’s disease [5-9]. The activation of microglia to a beneficial or detrimental phenotype can be described in terms of inducible protein expression, morphology, and functional outcomes such as cytokine production and phagocytosis [8,10].…”

Section: Introductionmentioning

confidence: 99%

M-CSF increases proliferation and phagocytosis while modulating receptor and transcription factor expression in adult human microglia

Smith

Gibbons

Oldfield³

et al. 2013

J Neuroinflammation

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BackgroundMicroglia are the primary immune cells of the brain whose phenotype largely depends on their surrounding micro-environment. Microglia respond to a multitude of soluble molecules produced by a variety of brain cells. Macrophage colony-stimulating factor (M-CSF) is a cytokine found in the brain whose receptor is expressed by microglia. Previous studies suggest a critical role for M-CSF in brain development and normal functioning as well as in several disease processes involving neuroinflammation.MethodsUsing biopsy tissue from patients with intractable temporal epilepsy and autopsy tissue, we cultured primary adult human microglia to investigate their response to M-CSF. Mixed glial cultures were treated with 25 ng/ml M-CSF for 96 hours. Proliferation and phagocytosis assays, and high through-put immunocytochemistry, microscopy and image analysis were performed to investigate microglial phenotype and function.ResultsWe found that the phenotype of primary adult human microglia was markedly changed following exposure to M-CSF. A greater number of microglia were present in the M-CSF- treated cultures as the percentage of proliferating (BrdU and Ki67-positive) microglia was greatly increased. A number of changes in protein expression occurred following M-CSF treatment, including increased transcription factors PU.1 and C/EBPβ, increased DAP12 adaptor protein, increased M-CSF receptor (CSF-1R) and IGF-1 receptor, and reduced HLA-DP, DQ, DR antigen presentation protein. Furthermore, a distinct morphological change was observed with elongation of microglial processes. These changes in phenotype were accompanied by a functional increase in phagocytosis of Aβ1-42 peptide.ConclusionsWe show here that the cytokine M-CSF dramatically influences the phenotype of adult human microglia. These results pave the way for future investigation of M-CSF-related targets for human therapeutic benefit.

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“…It has been reported that factors such as oxidative stress, deregulated neuroinflammation and an elevated blood sugar level are related to changes in BDNF expression [67–69]. We included the following cerebrovascular risk confounders: age, homocysteine, total cholesterol, triglycerol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine, hemoglobin, vitamin B12, folate, and hemoglobin-A1C [36].…”

Section: Methodsmentioning

confidence: 99%

Dose-dependent genotype effects of BDNF Val66Met polymorphism on default mode network in early stage Alzheimer's disease

et al. 2016

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In humans, brain-derived neurotrophic factor (BDNF) has been shown to play a pivotal role in neurocognition, and its gene contains a functional polymorphism (Val66Met) that may explain individual differences in brain volume and memory-related activity.In this study, we enrolled 186 Alzheimer's disease (AD) patients who underwent 3D T1 magnetic resonance imaging, and explored the gray matter (GM) structural covariance networks (SCN). The patients were divided into three groups according to their genotype: Met/Met (n = 45), Val/Met (n = 86) and Val/Val (n = 55). Seed-based analysis was performed focusing on four SCN networks. Neurobehavioral scores served as the major outcome factor.Only peak cluster volumes of default mode medial temporal lobe network showed significant genotype interactions, of which the interconnected peak clusters showed dose-dependent genotype effects. There were also significant correlations between the cognitive test scores and interconnected-cluster volumes, especially in the orbitofrontal cortex.These findings support the hypothesis that BDNF rs6265 polymorphisms modulate entorhinal cortex-interconnected clusters and the valine allele was associated with stronger structural covariance patterns that determined the cognitive outcomes.

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Why mesial temporal lobe epilepsy with hippocampal sclerosis is progressive: Uncontrolled inflammation drives disease progression?

Cited by 69 publications

References 97 publications

Clinical significance of serological biomarkers and neuropsychological performances in patients with temporal lobe epilepsy

Clinical significance of serological biomarkers and neuropsychological performances in patients with temporal lobe epilepsy

M-CSF increases proliferation and phagocytosis while modulating receptor and transcription factor expression in adult human microglia

Dose-dependent genotype effects of BDNF Val66Met polymorphism on default mode network in early stage Alzheimer's disease

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