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Pathogenesis and Targeted Therapy of Epilepsy
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Pathogenesis and Targeted Therapy of Epilepsy

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 29469

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Dr. Prosper N'Gouemo

E-Mail Website
Guest Editor
Department of Physiology and Biophysics, Howard University School of Medicine, Washington, DC 20059, USA
Interests: ion channels; calcium signaling; epilepsy; alcohol withdrawal seizures; prenatal alcohol exposure; substance abuse
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,


I am pleased to invite you to participate in this Special Issue, “Pathogenesis and Targeted Therapy of Epilepsy”.

Epilepsy is a disorder of neuronal hyperexcitability characterized by spontaneous and recurrent seizures. Despite the substantial number of antiepileptic drugs available to treat this debilitating neurological condition, approximately 30% of patients developed therapy-resistant epilepsy to the current pharmacological treatments. Thus, there is an urgent need to develop new therapeutic approaches based on novel mechanisms of the pathogenesis of seizures. Voltage-gated ion channels and their related signaling play important roles in controlling neuronal hyperexcitability that leads to seizures and therefore is considered as potential molecular targets for the treatment of seizures and epilepsies.


This Special Issue seeks papers providing new insights into the roles of voltage-gated and ligand-gated ion channels and their related signaling in the pathogenesis and pathophysiology of epileptogenesis, acquired epilepsy, and inherited epilepsy.

Dr. Prosper N'Gouemo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • epileptogenesis
  • seizures
  • inherited epilepsy
  • acquired epilepsy
  • voltage-gated ion channels
  • ligand-gated ion channels

Published Papers (12 papers)

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Editorial

Jump to: Research, Review

2 pages, 162 KiB  
Editorial
Pathogenesis and Targeted Therapy of Epilepsy
by Prosper N’Gouemo
Biomedicines 2022, 10(12), 3134; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10123134 - 05 Dec 2022
Viewed by 1254
Abstract
The Biomedicines Special Issue (BSI) of “Pathogenesis and Targeted Therapy of Epilepsy” seeks papers providing new insights into the roles of voltage-gated and ligand-gated ion channels and their related signaling in the pathogenesis and pathophysiology of acquired epilepsy and inherited epilepsy [...] Full article
(This article belongs to the Special Issue Pathogenesis and Targeted Therapy of Epilepsy)

Research

Jump to: Editorial, Review

35 pages, 14082 KiB  
Article
MRI-Guided Electrode Implantation for Chronic Intracerebral Recordings in a Rat Model of Post−Traumatic Epilepsy—Challenges and Gains
by Xavier Ekolle Ndode-Ekane, Riikka Immonen, Elina Hämäläinen, Eppu Manninen, Pedro Andrade, Robert Ciszek, Tomi Paananen, Olli Gröhn and Asla Pitkänen
Biomedicines 2022, 10(9), 2295; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10092295 - 15 Sep 2022
Cited by 4 | Viewed by 1828
Abstract
Brain atrophy induced by traumatic brain injury (TBI) progresses in parallel with epileptogenesis over time, and thus accurate placement of intracerebral electrodes to monitor seizure initiation and spread at the chronic postinjury phase is challenging. We evaluated in adult male Sprague Dawley rats [...] Read more.
Brain atrophy induced by traumatic brain injury (TBI) progresses in parallel with epileptogenesis over time, and thus accurate placement of intracerebral electrodes to monitor seizure initiation and spread at the chronic postinjury phase is challenging. We evaluated in adult male Sprague Dawley rats whether adjusting atlas-based electrode coordinates on the basis of magnetic resonance imaging (MRI) increases electrode placement accuracy and the effect of chronic electrode implantations on TBI-induced brain atrophy. One group of rats (EEG cohort) was implanted with two intracortical (anterior and posterior) and a hippocampal electrode right after TBI to target coordinates calculated using a rat brain atlas. Another group (MRI cohort) was implanted with the same electrodes, but using T2-weighted MRI to adjust the planned atlas-based 3D coordinates of each electrode. Histological analysis revealed that the anterior cortical electrode was in the cortex in 83% (25% in targeted layer V) of the EEG cohort and 76% (31%) of the MRI cohort. The posterior cortical electrode was in the cortex in 40% of the EEG cohort and 60% of the MRI cohort. Without MRI-guided adjustment of electrode tip coordinates, 58% of the posterior cortical electrodes in the MRI cohort will be in the lesion cavity, as revealed by simulated electrode placement on histological images. The hippocampal electrode was accurately placed in 82% of the EEG cohort and 86% of the MRI cohort. Misplacement of intracortical electrodes related to their rostral shift due to TBI-induced cortical and hippocampal atrophy and caudal retraction of the brain, and was more severe ipsilaterally than contralaterally (p < 0.001). Total lesion area in cortical subfields targeted by the electrodes (primary somatosensory cortex, visual cortex) was similar between cohorts (p > 0.05). MRI-guided adjustment of coordinates for electrodes improved the success rate of intracortical electrode tip placement nearly to that at the acute postinjury phase (68% vs. 62%), particularly in the posterior brain, which exhibited the most severe postinjury atrophy. Overall, MRI-guided electrode implantation improved the quality and interpretation of the origin of EEG-recorded signals. Full article
(This article belongs to the Special Issue Pathogenesis and Targeted Therapy of Epilepsy)
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16 pages, 5113 KiB  
Article
Blockade of TASK-1 Channel Improves the Efficacy of Levetiracetam in Chronically Epileptic Rats
by Ji-Eun Kim and Tae-Cheon Kang
Biomedicines 2022, 10(4), 787; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10040787 - 28 Mar 2022
Cited by 3 | Viewed by 1536
Abstract
Tandem of P domains in a weak inwardly rectifying K+ channel (TWIK)-related acid sensitive K+-1 channel (TASK-1) is an outwardly rectifying K+ channel that acts in response to extracellular pH. TASK-1 is upregulated in the astrocytes (particularly in the [...] Read more.
Tandem of P domains in a weak inwardly rectifying K+ channel (TWIK)-related acid sensitive K+-1 channel (TASK-1) is an outwardly rectifying K+ channel that acts in response to extracellular pH. TASK-1 is upregulated in the astrocytes (particularly in the CA1 region) of the hippocampi of patients with temporal lobe epilepsy and chronically epilepsy rats. Since levetiracetam (LEV) is an effective inhibitor for carbonic anhydrase, which has a pivotal role in buffering of extracellular pH, it is likely that the anti-epileptic action of LEV may be relevant to TASK-1 inhibition, which remains to be elusive. In the present study, we found that LEV diminished the upregulated TASK-1 expression in the CA1 astrocytes of responders (whose seizure activities were responsive to LEV), but not non-responders (whose seizure activities were not controlled by LEV) in chronically epileptic rats. ML365 (a selective TASK-1 inhibitor) only reduced seizure duration in LEV non-responders, concomitant with astroglial TASK-1 downregulation. Furthermore, ML365 co-treatment with LEV decreased the duration, frequency and severity of spontaneous seizures in non-responders to LEV. To the best of our knowledge, our findings suggest, for the first time, that the up-regulation of TASK-1 expression in CA1 astrocytes may be involved in refractory seizures in response to LEV. This may be a potential target to improve responsiveness to LEV. Full article
(This article belongs to the Special Issue Pathogenesis and Targeted Therapy of Epilepsy)
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Graphical abstract

15 pages, 1343 KiB  
Article
Activation of Calcium-Activated Chloride Channels Suppresses Inherited Seizure Susceptibility in Genetically Epilepsy-Prone Rats
by Miracle Thomas, Mark Simms and Prosper N’Gouemo
Biomedicines 2022, 10(2), 449; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10020449 - 15 Feb 2022
Cited by 2 | Viewed by 1742
Abstract
Inherited seizure susceptibility in genetically epilepsy-prone rats (GEPR-3s) is associated with increased voltage-gated calcium channel currents suggesting a massive calcium influx resulting in increased levels of intraneuronal calcium. Cytosolic calcium, in turn, activates many processes, including chloride channels, to restore normal membrane excitability [...] Read more.
Inherited seizure susceptibility in genetically epilepsy-prone rats (GEPR-3s) is associated with increased voltage-gated calcium channel currents suggesting a massive calcium influx resulting in increased levels of intraneuronal calcium. Cytosolic calcium, in turn, activates many processes, including chloride channels, to restore normal membrane excitability and limit repetitive firing of the neurons. Here we used EACT and T16Ainh-A01, potent activator and inhibitor of calcium-activated channels transmembrane protein 16A (TMEM16A), respectively, to probe the role of these channels in the pathophysiology of acoustically evoked seizures in the GEPR-3s. We used adult male and female GEPR-3s. Acoustically evoked seizures consisted of wild running seizures (WRSs) that evolved into generalized tonic-clonic seizures (GTCSs) and eventually culminated into forelimb extension (partial tonic seizures). We found that acute EACT treatment at relatively higher tested doses significantly reduced the incidences of WRSs and GTCSs, and the seizure severity in male GEPR-3s. Furthermore, these antiseizure effects were associated with delayed seizure onset and reduced seizure duration. Interestingly, the inhibition of TMEM16A channels reversed EACT’s antiseizure effects on seizure latency and seizure duration. No notable antiseizure effects were observed in female GEPR-3s. Together, these findings suggest that activation of TMEM16A channels may represent a putative novel cellular mechanism for suppressing GTCSs. Full article
(This article belongs to the Special Issue Pathogenesis and Targeted Therapy of Epilepsy)
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19 pages, 3063 KiB  
Article
Increased TRPV1 Channels and FosB Protein Expression Are Associated with Chronic Epileptic Seizures and Anxiogenic-like Behaviors in a Preclinical Model of Temporal Lobe Epilepsy
by Willian Lazarini-Lopes, Gleice Kelli Silva-Cardoso, Christie Ramos Andrade Leite-Panissi and Norberto Garcia-Cairasco
Biomedicines 2022, 10(2), 416; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10020416 - 10 Feb 2022
Cited by 10 | Viewed by 2183
Abstract
Epilepsies are neurological disorders characterized by chronic seizures and their related neuropsychiatric comorbidities, such as anxiety. The Transient Receptor Potential Vanilloid type-1 (TRPV1) channel has been implicated in the modulation of seizures and anxiety-like behaviors in preclinical models. Here, we investigated the impact [...] Read more.
Epilepsies are neurological disorders characterized by chronic seizures and their related neuropsychiatric comorbidities, such as anxiety. The Transient Receptor Potential Vanilloid type-1 (TRPV1) channel has been implicated in the modulation of seizures and anxiety-like behaviors in preclinical models. Here, we investigated the impact of chronic epileptic seizures in anxiety-like behavior and TRPV1 channels expression in a genetic model of epilepsy, the Wistar Audiogenic Rat (WAR) strain. WARs were submitted to audiogenic kindling (AK), a preclinical model of temporal lobe epilepsy (TLE) and behavioral tests were performed in the open-field (OF), and light-dark box (LDB) tests 24 h after AK. WARs displayed increased anxiety-like behavior and TRPV1R expression in the hippocampal CA1 area and basolateral amygdala nucleus (BLA) when compared to control Wistar rats. Chronic seizures increased anxiety-like behaviors and TRPV1 and FosB expression in limbic and brainstem structures involved with epilepsy and anxiety comorbidity, such as the hippocampus, superior colliculus, and periaqueductal gray matter. Therefore, these results highlight previously unrecognized alterations in TRPV1 expression in brain structures involved with TLE and anxiogenic-like behaviors in a genetic model of epilepsy, the WAR strain, supporting an important role of TRPV1 in the modulation of neurological disorders and associated neuropsychiatric comorbidities. Full article
(This article belongs to the Special Issue Pathogenesis and Targeted Therapy of Epilepsy)
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24 pages, 10337 KiB  
Article
Peripheral Infection after Traumatic Brain Injury Augments Excitability in the Perilesional Cortex and Dentate Gyrus
by Ying Wang, Pedro Andrade and Asla Pitkänen
Biomedicines 2021, 9(12), 1946; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9121946 - 19 Dec 2021
Cited by 6 | Viewed by 2496
Abstract
Peripheral infections occur in up to 28% of patients with traumatic brain injury (TBI), which is a major etiology for structural epilepsies. We hypothesized that infection occurring after TBI acts as a “second hit” and facilitates post-traumatic epileptogenesis. Adult male Sprague–Dawley rats were [...] Read more.
Peripheral infections occur in up to 28% of patients with traumatic brain injury (TBI), which is a major etiology for structural epilepsies. We hypothesized that infection occurring after TBI acts as a “second hit” and facilitates post-traumatic epileptogenesis. Adult male Sprague–Dawley rats were subjected to lateral fluid-percussion injury or sham-operation. At 8 weeks post-injury, rats were treated with lipopolysaccharide (LPS, 5 mg/kg) to mimic Gram-negative peripheral infection. T2-weighted magnetic resonance imaging was used to detect the cortical lesion type (small focal inflammatory [TBIFI] vs. large cavity-forming [TBICF]). Spontaneous seizures were detected with video-electroencephalography, and seizure susceptibility was determined by the pentylenetetrazole (PTZ) test. Post-PTZ neuronal activation was assessed using c-Fos immunohistochemistry. LPS treatment increased the percentage of rats with PTZ-induced seizures among animals with TBIFI lesions (p < 0.05). It also increased the cumulative duration of PTZ-induced seizures (p < 0.01), particularly in the TBIFI group (p < 0.05). The number of c-Fos immunopositive cells was higher in the perilesional cortex of injured animals compared with sham-operated animals (p < 0.05), particularly in the TBI-LPS group (p < 0.05). LPS treatment increased the percentage of injured rats with bilateral c-Fos staining in the dentate gyrus (p < 0.05), particularly in the TBIFI group (p < 0.05). Our findings demonstrate that peripheral infection after TBI increases PTZ-induced seizure susceptibility and neuronal activation in the perilesional cortex and bilaterally in the dentate gyrus, particularly in animals with prolonged perilesional T2 enhancement. Our data suggest that treatment of infections and reduction of post-injury neuro-inflammation are important components of the treatment regimen aiming at preventing epileptogenesis after TBI. Full article
(This article belongs to the Special Issue Pathogenesis and Targeted Therapy of Epilepsy)
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17 pages, 4852 KiB  
Article
Short-Term Epileptiform Activity Potentiates Excitatory Synapses but Does Not Affect Intrinsic Membrane Properties of Pyramidal Neurons in the Rat Hippocampus In Vitro
by Julia L. Ergina, Dmitry V. Amakhin, Tatyana Y. Postnikova, Elena B. Soboleva and Aleksey V. Zaitsev
Biomedicines 2021, 9(10), 1374; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9101374 - 01 Oct 2021
Cited by 10 | Viewed by 1974
Abstract
Even brief epileptic seizures can lead to activity-dependent structural remodeling of neural circuitry. Animal models show that the functional plasticity of synapses and changes in the intrinsic excitability of neurons can be crucial for epileptogenesis. However, the exact mechanisms underlying epileptogenesis remain unclear. [...] Read more.
Even brief epileptic seizures can lead to activity-dependent structural remodeling of neural circuitry. Animal models show that the functional plasticity of synapses and changes in the intrinsic excitability of neurons can be crucial for epileptogenesis. However, the exact mechanisms underlying epileptogenesis remain unclear. We induced epileptiform activity in rat hippocampal slices for 15 min using a 4-aminopyridine (4-AP) in vitro model and observed hippocampal hyperexcitability for at least 1 h. We tested several possible mechanisms of this hyperexcitability, including changes in intrinsic membrane properties of neurons and presynaptic and postsynaptic alterations. Neither input resistance nor other essential biophysical properties of hippocampal CA1 pyramidal neurons were affected by epileptiform activity. The glutamate release probability also remained unchanged, as the frequency of miniature EPSCs and the paired amplitude ratio of evoked responses did not change after epileptiform activity. However, we found an increase in the AMPA/NMDA ratio, suggesting alterations in the properties of postsynaptic glutamatergic receptors. Thus, the increase in excitability of hippocampal neural networks is realized through postsynaptic mechanisms. In contrast, the intrinsic membrane properties of neurons and the probability of glutamate release from presynaptic terminals are not affected in a 4-AP model. Full article
(This article belongs to the Special Issue Pathogenesis and Targeted Therapy of Epilepsy)
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22 pages, 4871 KiB  
Article
AMPA Receptor Antagonists Facilitate NEDD4-2-Mediated GRIA1 Ubiquitination by Regulating PP2B-ERK1/2-SGK1 Pathway in Chronic Epilepsy Rats
by Ji-Eun Kim, Duk-Shin Lee, Hana Park, Tae-Hyun Kim and Tae-Cheon Kang
Biomedicines 2021, 9(8), 1069; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9081069 - 23 Aug 2021
Cited by 5 | Viewed by 2421
Abstract
The neural precursor cell expressed by developmentally downregulated gene 4-2 (NEDD4-2) is a ubiquitin E3 ligase that has a high affinity toward binding and ubiquitinating glutamate ionotropic receptor α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type subunit 1 (GRIA1, also referred to GluR1 or GluA1). Since dysregulation [...] Read more.
The neural precursor cell expressed by developmentally downregulated gene 4-2 (NEDD4-2) is a ubiquitin E3 ligase that has a high affinity toward binding and ubiquitinating glutamate ionotropic receptor α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type subunit 1 (GRIA1, also referred to GluR1 or GluA1). Since dysregulation of GRIA1 surface expression is relevant to the responsiveness to AMPA receptor (AMPAR) antagonists (perampanel and GYKI 52466) in chronic epilepsy rats, it is likely that NEDD4-2 may be involved in the pathogenesis of intractable epilepsy. However, the role of NEDD4-2-mediated GRIA1 ubiquitination in refractory seizures to AMPAR antagonists is still unknown. In the present study, both AMPAR antagonists recovered the impaired GRIA1 ubiquitination by regulating protein phosphatase 2B (PP2B)-extracellular signal-regulated kinase 1/2 (ERK1/2)-serum and glucocorticoid-regulated kinase 1 (SGK1)-NEDD4-2 signaling pathway in responders (whose seizure activities are responsive to AMPAR), but not non-responders (whose seizure activities were uncontrolled by AMPAR antagonists). In addition, cyclosporin A (CsA, a PP2B inhibitor) co-treatment improved the effects of AMPAR antagonists in non-responders, independent of AKT signaling pathway. Therefore, our findings suggest that dysregulation of PP2B-ERK1/2-SGK1-NEDD4-2-mediated GRIA1 ubiquitination may be responsible for refractory seizures and that this pathway may be a potential therapeutic target for improving the treatment of intractable epilepsy in response to AMPAR antagonists. Full article
(This article belongs to the Special Issue Pathogenesis and Targeted Therapy of Epilepsy)
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22 pages, 6763 KiB  
Article
Inhibition of AKT/GSK3β/CREB Pathway Improves the Responsiveness to AMPA Receptor Antagonists by Regulating GRIA1 Surface Expression in Chronic Epilepsy Rats
by Ji-Eun Kim, Duk-Shin Lee, Hana Park, Tae-Hyun Kim and Tae-Cheon Kang
Biomedicines 2021, 9(4), 425; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9040425 - 14 Apr 2021
Cited by 14 | Viewed by 2572
Abstract
α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) has been reported as one of the targets for treatment of epilepsy. Although maladaptive regulation of surface expression of glutamate ionotropic receptor AMPA type subunit 1 (GRIA1) subunit is relevant to the responsiveness to AMPAR antagonists (perampanel and GYKI [...] Read more.
α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) has been reported as one of the targets for treatment of epilepsy. Although maladaptive regulation of surface expression of glutamate ionotropic receptor AMPA type subunit 1 (GRIA1) subunit is relevant to the responsiveness to AMPAR antagonists (perampanel and GYKI 52466) in LiCl-pilocarpine-induced chronic epilepsy rats, the underlying mechanisms of refractory seizures to AMPAR antagonists have yet been unclear. In the present study, we found that both AMPAR antagonists restored the up-regulations of GRIA1 surface expression and Src family-mediated glycogen synthase kinase 3β (GSK3β)-Ca2+/cAMP response element-binding protein (CREB) phosphorylations to control levels in responders (whose seizure activities were responsive to AMPAR) but not non-responders (whose seizure activities were uncontrolled by AMPAR antagonists). In addition, 3-chloroacetyl indole (3CAI, an AKT inhibitor) co-treatment attenuated spontaneous seizure activities in non-responders, accompanied by reductions in AKT/GSK3β/CREB phosphorylations and GRIA1 surface expression. Although AMPAR antagonists reduced GRIA2 tyrosine (Y) phosphorylations in responders, they did not affect GRIA2 surface expression and protein interacting with C kinase 1 (PICK1) protein level in both responders and non-responders. Therefore, our findings suggest that dysregulation of AKT/GSK3β/CREB-mediated GRIA1 surface expression may be responsible for refractory seizures in non-responders, and that this pathway may be a potential target to improve the responsiveness to AMPAR antagonists. Full article
(This article belongs to the Special Issue Pathogenesis and Targeted Therapy of Epilepsy)
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Review

Jump to: Editorial, Research

20 pages, 805 KiB  
Review
Targeting the Ghrelin Receptor as a Novel Therapeutic Option for Epilepsy
by An Buckinx, Dimitri De Bundel, Ron Kooijman and Ilse Smolders
Biomedicines 2022, 10(1), 53; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10010053 - 27 Dec 2021
Cited by 7 | Viewed by 3800
Abstract
Epilepsy is a neurological disease affecting more than 50 million individuals worldwide. Notwithstanding the availability of a broad array of antiseizure drugs (ASDs), 30% of patients suffer from pharmacoresistant epilepsy. This highlights the urgent need for novel therapeutic options, preferably with an emphasis [...] Read more.
Epilepsy is a neurological disease affecting more than 50 million individuals worldwide. Notwithstanding the availability of a broad array of antiseizure drugs (ASDs), 30% of patients suffer from pharmacoresistant epilepsy. This highlights the urgent need for novel therapeutic options, preferably with an emphasis on new targets, since “me too” drugs have been shown to be of no avail. One of the appealing novel targets for ASDs is the ghrelin receptor (ghrelin-R). In epilepsy patients, alterations in the plasma levels of its endogenous ligand, ghrelin, have been described, and various ghrelin-R ligands are anticonvulsant in preclinical seizure and epilepsy models. Up until now, the exact mechanism-of-action of ghrelin-R-mediated anticonvulsant effects has remained poorly understood and is further complicated by multiple downstream signaling pathways and the heteromerization properties of the receptor. This review compiles current knowledge, and discusses the potential mechanisms-of-action of the anticonvulsant effects mediated by the ghrelin-R. Full article
(This article belongs to the Special Issue Pathogenesis and Targeted Therapy of Epilepsy)
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14 pages, 1070 KiB  
Review
Rodent Brain Pathology, Audiogenic Epilepsy
by Irina B. Fedotova, Natalia M. Surina, Georgy M. Nikolaev, Alexandre V. Revishchin and Inga I. Poletaeva
Biomedicines 2021, 9(11), 1641; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9111641 - 08 Nov 2021
Cited by 12 | Viewed by 1821
Abstract
The review presents data which provides evidence for the internal relationship between the stages of rodent audiogenic seizures and post-ictal catalepsy with the general pattern of animal reaction to the dangerous stimuli and/or situation. The wild run stage of audiogenic seizure fit could [...] Read more.
The review presents data which provides evidence for the internal relationship between the stages of rodent audiogenic seizures and post-ictal catalepsy with the general pattern of animal reaction to the dangerous stimuli and/or situation. The wild run stage of audiogenic seizure fit could be regarded as an intense panic reaction, and this view found support in numerous experimental data. The phenomenon of audiogenic epilepsy probably attracted the attention of physiologists as rodents are extremely sensitive to dangerous sound stimuli. The seizure proneness in this group shares common physiological characteristics and depends on animal genotype. This concept could be the new platform for the study of epileptogenesis mechanisms. Full article
(This article belongs to the Special Issue Pathogenesis and Targeted Therapy of Epilepsy)
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16 pages, 2628 KiB  
Review
The Neuroinflammatory Role of Pericytes in Epilepsy
by Gaku Yamanaka, Fuyuko Takata, Yasufumi Kataoka, Kanako Kanou, Shinichiro Morichi, Shinya Dohgu and Hisashi Kawashima
Biomedicines 2021, 9(7), 759; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9070759 - 30 Jun 2021
Cited by 23 | Viewed by 3947
Abstract
Pericytes are a component of the blood–brain barrier (BBB) neurovascular unit, in which they play a crucial role in BBB integrity and are also implicated in neuroinflammation. The association between pericytes, BBB dysfunction, and the pathophysiology of epilepsy has been investigated, and links [...] Read more.
Pericytes are a component of the blood–brain barrier (BBB) neurovascular unit, in which they play a crucial role in BBB integrity and are also implicated in neuroinflammation. The association between pericytes, BBB dysfunction, and the pathophysiology of epilepsy has been investigated, and links between epilepsy and pericytes have been identified. Here, we review current knowledge about the role of pericytes in epilepsy. Clinical evidence has shown an accumulation of pericytes with altered morphology in the cerebral vascular territories of patients with intractable epilepsy. In vitro, proinflammatory cytokines, including IL-1β, TNFα, and IL-6, cause morphological changes in human-derived pericytes, where IL-6 leads to cell damage. Experimental studies using epileptic animal models have shown that cerebrovascular pericytes undergo redistribution and remodeling, potentially contributing to BBB permeability. These series of pericyte-related modifications are promoted by proinflammatory cytokines, of which the most pronounced alterations are caused by IL-1β, a cytokine involved in the pathogenesis of epilepsy. Furthermore, the pericyte-glial scarring process in leaky capillaries was detected in the hippocampus during seizure progression. In addition, pericytes respond more sensitively to proinflammatory cytokines than microglia and can also activate microglia. Thus, pericytes may function as sensors of the inflammatory response. Finally, both in vitro and in vivo studies have highlighted the potential of pericytes as a therapeutic target for seizure disorders. Full article
(This article belongs to the Special Issue Pathogenesis and Targeted Therapy of Epilepsy)
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