Circulating P2X7 Receptor Signaling Components as Diagnostic Biomarkers for Temporal Lobe Epilepsy

Circulating molecules have potential as biomarkers to support the diagnosis of epilepsy and to assist with differential diagnosis, for example, in conditions resembling epilepsy, such as in psychogenic non-epileptic seizures (PNES). The P2X7 receptor (P2X7R) is an important regulator of inflammation and mounting evidence supports its activation in the brain during epilepsy. Whether the P2X7R or P2X7R-dependent signaling molecules can be used as biomarkers of epilepsy has not been reported. P2X7R levels were analyzed by quantitative ELISA using plasma samples from controls and patients with temporal lobe epilepsy (TLE) or PNES. Moreover, blood cell P2X7R expression and P2X7R-dependent cytokine signature was measured following status epilepticus in P2X7R-EGFP reporter, wildtype, and P2X7R-knockout mice. P2X7R plasma levels were higher in TLE patients when compared with controls and patients with PNES. Plasma levels of the broad inflammatory marker protein C-Reactive protein (CRP) were similar between the three groups. Using P2X7R-EGFP reporter mice, we identified monocytes as the main blood cell type expressing P2X7R after experimentally evoked seizures. Finally, cytokine array analysis in P2X7R-deficient mice identified KC/GRO as a potential P2X7R-dependent plasma biomarker following status epilepticus and during epilepsy. Our data suggest that P2X7R signaling components may be a promising subclass of circulating biomarkers to support the diagnosis of epilepsy.

Download Full-text

Wide-band EEG analysis of epileptic seizures during pilocarpine-induced acute status epilepticus and chronic temporal lobe epilepsy in rats

Proceedings for Annual Meeting of The Japanese Pharmacological Society ◽

10.1254/jpssuppl.92.0_3-p-003 ◽

2019 ◽

Vol 92 (0) ◽

pp. 3-P-003

Author(s):

Kazuaki Sato ◽

Masato Kinboshi ◽

Masao Matsuhashi ◽

Akio Ikeda ◽

Higor A Iha ◽

...

Keyword(s):

Status Epilepticus ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Epileptic Seizures ◽

Wide Band ◽

Eeg Analysis

Download Full-text

Analysis of the acute neuroinflammatory response and endogenous markers in the amygdala of animals submitted to status epilepticus by intrahippocampal pilocarpine application

MedNEXT Journal of Medical and Health Sciences ◽

10.54448/mdnt21623 ◽

2021 ◽

Vol 2 (6) ◽

Author(s):

Vinicius Lisboa Da Rocha ◽

Amanda Pinato Alves da Costa ◽

Amanda Feltrin Lisboa ◽

Enzo Da Silva Salmazo ◽

Emanoel de Oliveira Araújo ◽

...

Keyword(s):

Status Epilepticus ◽

Temporal Lobe Epilepsy ◽

Experimental Model ◽

Temporal Lobe ◽

Inflammatory Process ◽

Epileptic Seizures ◽

Immunohistochemical Analysis ◽

Sterile Saline ◽

Male Wistar Rats ◽

The Right

Introduction: Experimental evidence and clinical evidence indicate that the inflammatory process is a crucial mechanism in the pathophysiology of epileptic seizures and temporal lobe epilepsy. The amygdala when involved in an atypical processing is associated with multiple moods such as depression and anxiety disorder and psychiatric disorders such as schizophrenia. Objective: This study investigated the acute inflammatory process and modulation of the endogenous proteins’ galectins and AnxA1 in the amygdala of animals submitted to an experimental model of temporal lobe epilepsy. Methods: The experimental procedures were approved by the Ethics Committee on the Use of Animals at UNIFESP (CEUA nº2958050814). The experiments performed in this study used data and materials that were obtained from the project “Neuroprotective and anti-inflammatory role of the mimetic peptide ac2-26 of the annexin a1 protein in intrahippocampal pilocarpine-induced status epilepticus” conducted by the advisor. The experimental model used male Wistar rats that were divided into 3 experimental groups (NAIVE; SHAM, Status Epilepticus or SE - n = 5 animals/group). Once acclimated, the animals in the SHAM and SE groups underwent stereotaxic surgery for implantation of the intracerebral cannula in the right hippocampus. The SHAM animals received sterile saline in all procedures and the NAIVE group only manipulated. The animals were monitored throughout the period and after 24 hours of experiment all animals were euthanized by overdose of thiopental to remove the brain and performed histological and immunohistochemical analysis. Results and Conclusion: Initial results demonstrate that SE and the acute inflammatory process cause damage to the amygdala, and there is also modulation of inflammatory markers in this structure. However, further studies are needed to better understand the mechanism of action in neuroinflammation in status epilepticus.

Download Full-text

Prophylactic treatment with melatonin after status epilepticus: Effects on epileptogenesis, neuronal damage, and behavioral changes in a kainate model of temporal lobe epilepsy

Epilepsy & Behavior ◽

10.1016/j.yebeh.2013.01.009 ◽

2013 ◽

Vol 27 (1) ◽

pp. 174-187 ◽

Cited By ~ 35

Author(s):

Jana Tchekalarova ◽

Zlatina Petkova ◽

Daniela Pechlivanova ◽

Slavianka Moyanova ◽

Lidia Kortenska ◽

...

Keyword(s):

Status Epilepticus ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Prophylactic Treatment ◽

Neuronal Damage ◽

Behavioral Changes

Download Full-text

Ictal ECG changes in temporal lobe epilepsy

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x1995000400012 ◽

1995 ◽

Vol 53 (3b) ◽

pp. 619-624 ◽

Cited By ~ 14

Author(s):

L.M. Li ◽

J. Roche ◽

J.W.A.S. Sander

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Sinus Bradycardia ◽

Cardiac Pacemaker ◽

Epileptic Seizures ◽

Ecg Changes ◽

Unexpected Death ◽

Complex Partial Seizures ◽

The Mean ◽

Video Eeg

Changes in cardiac rhythm may occur during epileptic seizures and this has been suggested as a possible mechanism for sudden unexpected death amongst patients with chronic epilepsy (SUDEP). We have studied ECG changes during 61 complex partial seizures of temporal lobe origin in 20 patients. Tachycardia was observed in 24/61 (39%) and bradycardia in 3/61 (5%). The mean and median tachycardia rate was 139 and 140 beats/min (range 120-180). The longest R-R interval observed was 9 seconds. No difference was found in regard to the lateralisation of seizures and cardiac arrhytmia. One of the patients with bradycardia was fitted with a demand cardiac pacemaker, which appeared to decrease the number of his falls. In conclusion, ictal cardiac changes which may be seen in temporal lobe epilepsy (TLE) are sinus tachycardia and occasionally sinus bradycardia. Patients presenting vague complains suggestive of either TLE or cardiac dysrhythmia, simultaneous monitoring with EEG/ECG is required, and if the episodes are frequent, video-EEG should be considered. Further studies on this subject are warranted as this may shed some light on possible mechanisms for SUDEP.

Download Full-text

Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model

Antioxidants ◽

10.3390/antiox10111702 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1702

Author(s):

Sereen Sandouka ◽

Tawfeeq Shekh-Ahmad

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Status Epilepticus ◽

Temporal Lobe Epilepsy ◽

Antioxidant Capacity ◽

Temporal Lobe ◽

Epileptiform Activity ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

The Brain

Epilepsy is a chronic disease of the brain that affects over 65 million people worldwide. Acquired epilepsy is initiated by neurological insults, such as status epilepticus, which can result in the generation of ROS and induction of oxidative stress. Suppressing oxidative stress by upregulation of the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown to be an effective strategy to increase endogenous antioxidant defences, including in brain diseases, and can ameliorate neuronal damage and seizure occurrence in epilepsy. Here, we aim to test the neuroprotective potential of a naturally occurring Nrf2 activator sulforaphane, in in vitro epileptiform activity model and a temporal lobe epilepsy rat model. Sulforaphane significantly decreased ROS generation during epileptiform activity, restored glutathione levels, and prevented seizure-like activity-induced neuronal cell death. When given to rats after 2 h of kainic acid-induced status epilepticus, sulforaphane significantly increased the expression of Nrf2 and related antioxidant genes, improved oxidative stress markers, and increased the total antioxidant capacity in both the plasma and hippocampus. In addition, sulforaphane significantly decreased status epilepticus-induced neuronal cell death. Our results demonstrate that Nrf2 activation following an insult to the brain exerts a neuroprotective effect by reducing neuronal death, increasing the antioxidant capacity, and thus may also modify epilepsy development.

Download Full-text

Close relationship between initial convulsive status epilepticus in early childhood and the later development of mesial temporal lobe epilepsy

Brain and Development ◽

10.1016/s0387-7604(97)82996-8 ◽

1996 ◽

Vol 18 (6) ◽

pp. 472 ◽

Cited By ~ 1

Author(s):

Tateki Fujiwara ◽

Takayasu Tottori ◽

Yuko Kuboto ◽

Kazumi Matsuda ◽

Tadahiro Mihara ◽

...

Keyword(s):

Early Childhood ◽

Status Epilepticus ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Mesial Temporal Lobe Epilepsy ◽

Convulsive Status Epilepticus ◽

Close Relationship ◽

Mesial Temporal Lobe

Download Full-text

Grafting of striatal precursor cells into hippocampus shortly after status epilepticus restrains chronic temporal lobe epilepsy

Experimental Neurology ◽

10.1016/j.expneurol.2008.04.040 ◽

2008 ◽

Vol 212 (2) ◽

pp. 468-481 ◽

Cited By ~ 64

Author(s):

Bharathi Hattiangady ◽

Muddanna S. Rao ◽

Ashok K. Shetty

Keyword(s):

Status Epilepticus ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Precursor Cells

Download Full-text

Animal models of status epilepticus and temporal lobe epilepsy: a narrative review

Reviews in the Neurosciences ◽

10.1515/revneuro-2017-0086 ◽

2018 ◽

Vol 29 (7) ◽

pp. 757-770 ◽

Cited By ~ 11

Author(s):

Nikita Nirwan ◽

Preeti Vyas ◽

Divya Vohora

Keyword(s):

Animal Model ◽

Status Epilepticus ◽

Animal Models ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Current Literature ◽

Clinical Characteristics ◽

Genetic Models ◽

Suitable Animal Model ◽

Effective Models

Abstract Temporal lobe epilepsy (TLE) is the chronic and pharmacoresistant form of epilepsy observed in humans. The current literature is insufficient in explicating the comprehensive mechanisms underlying its pathogenesis and advancement. Consequently, the development of a suitable animal model mimicking the clinical characteristics is required. Further, the relevance of status epilepticus (SE) to animal models is dubious. SE occurs rarely in people; most epilepsy patients never experience it. The present review summarizes the established animal models of SE and TLE, along with a brief discussion of the animal models that have the distinctiveness and carries the possibility to be developed as effective models for TLE. The review not only covers the basic requirements, mechanisms, and methods of induction of each model but also focuses upon their major limitations and possible modifications for their future use. A detailed discussion on chemical, electrical, and hypoxic/ischemic models as well as a brief explanation on the genetic models, most of which are characterized by development of SE followed by neurodegeneration, is presented.

Download Full-text