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

Abstract

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/.

The Impacts of Surgery and Intracerebral Electrodes in C57BL/6J Mouse Kainate Model of Epileptogenesis: Seizure Threshold, Proteomics, and Cytokine Profiles

“…The increased expression of CysC was observed in glial cells in the molecular layer of the dentate gyrus and associated with granule cell dispersion in both rat model and human patients with TLE ( 4 ). High levels of CatB were reported in serum of human patients with surgically resected temporal lobes ( 59 ) and in glial cells of progressive myoclonic epilepsies ( 57 ), suggesting that CatB can be a potential therapeutic target for certain epilepsies ( 58 ).…”

The correlation of temporal changes of neutrophil-lymphocyte ratio with seizure severity and the following seizure tendency in patients with epilepsy

“…We found that systemic inflammatory responses reflected by NLR remained increased during 5–14 days of follow-up after acute seizures compared with healthy controls. Some studies have also found that NLR level is higher in patients with chronic temporal lobe epilepsy than in healthy controls ( 39 ). Accordingly, it is suggested that the long-lasting systemic inflammatory response induced by acute seizures may be involved in the process of epileptogenesis either in the acute stages or in the chronic stages.…”

Modulation of Neuro-Inflammatory Signals in Microglia by Plasma Prekallikrein and Neuronal Cell Debris

“…The role and contribution of PKall to aging and neurodegenerative disorders are still being unraveled ( Albert-Weissenberger et al, 2014 ; Nokkari et al, 2018 ; Strickland 2018 ). Higher levels of circulating PKall activity were associated with augmented KNG cleavage resulting in the greater generation of BK levels which could influence vascular dysregulation in states of neurodegenerative diseases ( Zamolodchikov et al, 2015 ; Simoes et al, 2019 ; Park et al, 2021 ). Mice lacking the PKall gene (klkb1), displayed reduced brain infarctions and fewer neurological shortfalls compared to wild-type mice when subjected to brief central cerebral artery obstruction ( Gob et al, 2015 ).…”