Peripheral leukocyte profile in people with temporal lobe epilepsy reflects the associated proinflammatory state

Vieira, Érica Leandro Marciano; Oliveira, Guilherme Nogueira Mendes de; Lessa, João Marcelo K.; Gonçalves, Ana Paula; Oliveira, Antônio Carlos Pinheiro de; Bauer, Moisés Evandro; Sander, Josemir W.; Cendes, Fernando; Teixeira, Antônio Lúcio

doi:10.1016/j.bbi.2015.11.016

Cited by 42 publications

(28 citation statements)

References 41 publications

(37 reference statements)

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“…Bradykinin can induce the release of NO, thereby inducing disruption of the BBB and the entry of lymphocytes, macrophages, T‐lymphocytes, neutrophils, and granulocytes into the brain tissue as shown in Fig. (a–h) and reported in other studies (Varella et al ; Vieira et al ). These blood cells invade the hippocampal tissue and induce inflammation.…”

Section: Discussionsupporting

confidence: 64%

“…Thus, bradykinin, which is produced in the brain or blood, can disrupt the BBB, thereby inducing brain inflammation which is characterized by gliosis, increased production of cytokines (Vezzani and Friedman 2011;Vezzani et al 2013;Vezzani 2015), complement activation (Davis et al 2010), and infiltration of blood cells into the hippocampus, as shown in Fig. 1 (A-H) and reported by other authors (Viviani et al 2003;Varella et al 2011;Zattoni et al 2011;Vieira et al 2016). The brain is thereby connected to peripheral inflammation, as expressed by increased levels of C-reactive protein, increased ratio of neutrophils/lymphocytes in the blood, increased circulating bradykinin, and increased activity of PKal and CatB.…”

Section: Discussionmentioning

confidence: 62%

“…Previous studies have also reported increased levels of kinins, corresponding receptors, and antibodies against kinin in the brain of patients with other neurodegenerative conditions, such as ischemia and Alzheimer’s disease (Myagkova et al ; Gröger et al ), which are also linked to inflammation. Studying the inflammatory response in the blood of patients with TLE, Vieira et al found increased expression of cytokines interleukin 6 (IL‐6), interferon gamma (IFN‐γ), tumor necrosis factor (TNF), and interleukin 17A (IL‐17A) in lymphocytes and monocytes. These findings are consistent with those of other studies that report elevated cytokine levels in the brain and serum/plasma of patients with TLE (Balosso et al ; Vezzani et al, ).…”

Section: Discussionmentioning

confidence: 99%

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Plasma kallikrein‐kinin system contributes to peripheral inflammation in temporal lobe epilepsy

Simões¹,

Zanelatto²,

Assis³

et al. 2019

Journal of Neurochemistry

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Temporal lobe epilepsy (TLE) is a chronic disease, characterized by severe and refractory seizures, triggered in the hippocampus and/or amygdala, disrupting the blood–brain barrier. This disruption can sustain, or aggravate, the epileptic condition. The aim of this study was to evaluate the activation of the kallikrein‐kinin system in patients with TLE, as it relates to the maintenance of blood–brain barrier. Human hippocampal sclerotic tissues removed after surgery for seizure control, plasma, and serum were used in the following assays: immunostaining for white blood cells in the TLE hippocampus, C‐reactive protein in serum, quantification of plasma kallikrein (PKal) and cathepsin B (CatB) activity in serum and plasma, quantification of C1‐inhibitor, analysis of high‐molecular‐weight kininogen (H‐kininogen) fragments, and activation of plasma prekallikrein for comparison with healthy controls. Infiltration of white blood cells in the sclerotic hippocampus and a significant increase in the neutrophil/lymphocyte ratio in the blood of TLE patients were observed. High levels of C‐reactive protein (TLE = 1.4 ± 0.3 µg/mL), PKal (TLE = 5.4 ± 0.4 U/mL), and CatB (TLE = 4.9 ± 0.4 U/mL) were also evident in the serum of TLE patients comparing to controls. A strong linear correlation was observed between active CatB and PKal in the serum of TLE patients (r = 0.88). High levels of cleaved H‐kininogen and free PKal, and low levels of C1‐inhibitor (TLE = 188 ± 12 µg/mL) were observed in the serum of TLE patients. Our data demonstrated that the plasma kallikrein‐kinin system is activated in patients with TLE. Open Science Badges This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Plasma kallikrein‐kinin system contributes to peripheral inflammation in temporal lobe epilepsy

Simões¹,

Zanelatto²,

Assis³

et al. 2019

Journal of Neurochemistry

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“…Additionally, patients with temporal lobe epilepsy have also been reported to have increased levels of interferon gamma (Vieira et al, 2016). However, the effects of MgSO 4 treatment on these cytokines have not been assessed.…”

Section: Discussionmentioning

confidence: 99%

Magnesium Sulfate Prevents Placental Ischemia-Induced Increases in Brain Water Content and Cerebrospinal Fluid Cytokines in Pregnant Rats

Zhang

Warrington

2016

Front. Neurosci.

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Magnesium sulfate (MgSO4) is the most widely used therapy in the clinic to prevent the progression of preeclampsia, a hypertensive disorder of pregnancy, to eclampsia. Eclampsia, manifested as unexplained seizures and/or coma during pregnancy or postpartum, accounts for ~13% of maternal deaths worldwide. While MgSO4 continues to be used in the clinic, the mechanisms by which it exerts its protective actions are not well understood. In this study, we tested the hypothesis that MgSO4 protects against placental ischemia-induced increases in brain water content and cerebrospinal fluid cytokines. To test this hypothesis, MgSO4 was administered via mini-osmotic pump (60 mg/day, i.p.) to pregnant and placental ischemic rats, induced by mechanical reduction of uterine perfusion pressure, from gestational day 14–19. This treatment regimen of MgSO4 led to therapeutic level of 2.8 ± 0.6 mmol/L Mg in plasma. MgSO4 had no effect on improving placental ischemia-induced changes in mean arterial pressure, number of live fetuses, or fetal and placental weight. Placental ischemia increased, while MgSO4 prevented the increase in water content in the anterior cerebrum. Cytokine and chemokine levels were measured in the cerebrospinal fluid using a multi-plex assay. Results demonstrate that cerebrospinal fluid, obtained via the cisterna magna, had reduced protein, albumin, interleukin (IL)-17A, IL-18, IL-2, eotaxin, fractalkine, interferon gamma, vascular endothelial growth factor (VEGF), and macrophage inflammatory protein (MIP)-2 following MgSO4 treatment. These data support the hypothesis that MgSO4 offers neuroprotection by preventing placental ischemia-induced cerebral edema and reducing levels of cytokines/chemokines in the cerebrospinal fluid.

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“…Several studies have demonstrated that the pro-inflammatory cytokines IL-1β, IL-6, TNF-α modulate susceptibility to limbic seizures in rodent models of temporal lobe epilepsy (133). These cytokines are also upregulated within the CNS during seizures along with markers of monocyte activation (CD86, HLA-DR, CD14 + CD16 − ) and T cell activation (CD25, CD69, CTLA-4, and HLA-DR) (134). One study examining status epilepticus (SE) induced in rats with kainic acid (KA, a commonly used molecule for inducing seizures in animal models) demonstrated infiltration of blood derived monocytes expressing CCR2 (135).…”

Section: Potential Role Of Innate Immune System Dysfunction In Autoimmentioning

confidence: 99%

Innate Immunity in the Central Nervous System: A Missing Piece of the Autoimmune Encephalitis Puzzle?

et al. 2019

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The autoimmune encephalitides are a group of autoimmune conditions targeting the central nervous system and causing severe clinical symptoms including drug-resistant seizures, cognitive dysfunction and psychiatric disturbance. Although these disorders appear to be antibody mediated, the role of innate immune responses needs further clarification. Infiltrating monocytes and microglial proliferation at the site of pathology could contribute to the pathogenesis of the disease with resultant blood brain barrier dysfunction, and subsequent activation of adaptive immune response. Both innate and adaptive immune cells can produce pro-inflammatory molecules which can perpetuate ongoing neuroinflammation and drive ongoing seizure activity. Ultimately neurodegenerative changes can ensue with resultant long-term neurological sequelae that can impact on ongoing patient morbidity and quality of life, providing a potential target for future translational research.

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Peripheral leukocyte profile in people with temporal lobe epilepsy reflects the associated proinflammatory state

Cited by 42 publications

References 41 publications

Plasma kallikrein‐kinin system contributes to peripheral inflammation in temporal lobe epilepsy

Plasma kallikrein‐kinin system contributes to peripheral inflammation in temporal lobe epilepsy

Magnesium Sulfate Prevents Placental Ischemia-Induced Increases in Brain Water Content and Cerebrospinal Fluid Cytokines in Pregnant Rats

Innate Immunity in the Central Nervous System: A Missing Piece of the Autoimmune Encephalitis Puzzle?

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