Transcranial direct current stimulation (tDCS) affects neuroinflammation parameters and behavioral seizure activity in pentylenetetrazole-induced kindling in rats

Regner, Gabriela Gregory; Torres, Iraci Lucena da Silva; Oliveira, Carla de; Pflüger, Pricila; Silva, Lisiane Santos da; Scarabelot, Vanessa Leal; Ströher, Roberta; Souza, Andressa de; Fregni, Felipe; Pereira, Patrı́cia

doi:10.1016/j.neulet.2020.135162

Cited by 18 publications

(15 citation statements)

References 79 publications

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“…All records included in this review used rat models of epilepsy. More precisely, the used models consisted in: cortical-ramp stimulation to induce focal epilepsy (1 record, Liebetanz et al, 2006 ); spontaneous recurring spike-wave patterns (2 records, Berényi et al, 2012 ; Kozák and Berényi, 2017 ); WAG/Rij genetically modified rats (1 record, Zobeiri and van Luijtelaar, 2013 ) as model of absence epilepsy; lithium-pilocarpine (1 record, Kamida et al, 2011 ) and kainic acid (1 record: Wu et al, 2020 ) as status epilepticus models; pentylenetetrazol (2 records: Dhamne et al, 2015 ; Regner et al, 2020 ) as a model of either acute or chronic generalized seizures.…”

Section: Resultsmentioning

confidence: 99%

“…Cathodal tDCS efficiently increased the threshold of seizure triggering and latency of the first seizure after epilepsy induction (Liebetanz et al, 2006 ; Dhamne et al, 2015 ; Regner et al, 2020 ; Wu et al, 2020 ). Other outcomes concerned decrease in seizure duration, frequency, and severity (Kamida et al, 2011 ; Dhamne et al, 2015 ; Wu et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…Despite the positive results in seizure rate and epileptiform discharges reduction when applied interictally, tES does not seem to be able to stop ongoing seizures (Dhamne et al, 2015 ). Nevertheless, some studies have shown the potential of tES combined with pharmacological treatment, demonstrating that adding either lorazepam (Dhamne et al, 2015 ) or diazepam (Regner et al, 2020 ) to the tDCS stimulation can efficiently increase the antiepileptic effects of stimulation (abortion of seizures, threshold increase for the first seizure). Therefore, association of tDCS with pharmacological treatment may potentially reduce drug doses and thus, the drug's side effects.…”

Section: Resultsmentioning

confidence: 99%

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Transcranial current stimulation in epilepsy: A systematic review of the fundamental and clinical aspects

Simula

Daoud

Ruffini³

et al. 2022

Front. Neurosci.

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PurposeTranscranial electrical current stimulation (tES or tCS, as it is sometimes referred to) has been proposed as non-invasive therapy for pharmacoresistant epilepsy. This technique, which includes direct current (tDCS) and alternating current (tACS) stimulation involves the application of weak currents across the cortex to change cortical excitability. Although clinical trials have demonstrated the therapeutic efficacy of tES, its specific effects on epileptic brain activity are poorly understood. We sought to summarize the clinical and fundamental effects underlying the application of tES in epilepsy.MethodsA systematic review was performed in accordance with the PRISMA guidelines. A database search was performed in PUBMED, MEDLINE, Web of Science and Cochrane CENTRAL for articles corresponding to the keywords “epilepsy AND (transcranial current stimulation OR transcranial electrical stimulation)”.ResultsA total of 56 studies were included in this review. Through these records, we show that tDCS and tACS epileptic patients are safe and clinically relevant techniques for epilepsy. Recent articles reported changes of functional connectivity in epileptic patients after tDCS. We argue that tDCS may act by affecting brain networks, rather than simply modifying local activity in the targeted area. To explain the mechanisms of tES, various cellular effects have been identified. Among them, reduced cell loss, mossy fiber sprouting, and hippocampal BDNF protein levels. Brain modeling and human studies highlight the influence of individual brain anatomy and physiology on the electric field distribution. Computational models may optimize the stimulation parameters and bring new therapeutic perspectives.ConclusionBoth tDCS and tACS are promising techniques for epilepsy patients. Although the clinical effects of tDCS have been repeatedly assessed, only one clinical trial has involved a consistent number of epileptic patients and little knowledge is present about the clinical outcome of tACS. To fill this gap, multicenter studies on tES in epileptic patients are needed involving novel methods such as personalized stimulation protocols based on computational modeling. Furthermore, there is a need for more in vivo studies replicating the tES parameters applied in patients. Finally, there is a lack of clinical studies investigating changes in intracranial epileptiform discharges during tES application, which could clarify the nature of tES-related local and network dynamics in epilepsy.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Transcranial current stimulation in epilepsy: A systematic review of the fundamental and clinical aspects

Simula

Daoud

Ruffini³

et al. 2022

Front. Neurosci.

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“…Benzer şekilde benzodiazepinlerin hipokampüste etki mekanizmasını araştıran bir çalışmada diazepamın BDNF seviyesini düşürdüğü gösterilmiştir [47]. Bu çalışmadan farklı olarak Regner ve arkadaşları PTZ ile oluşturulan tutuşma modelinde nöbet sonrası diazepam uygulan grubun PTZ grubuna göre kortikal ve hipokampal BDNF seviyeleri üzerine etki etmediğini belirtmişlerdir [48]. Çalışmamızda ise PTZ ile oluşturulan nöbet sonrasında korteks ve hipokampüste BDNF seviyesinin arttığı tespit edildi.…”

Section: Discussionunclassified

Pentilentetrazol ile Oluşturulan Akut Nöbet Modelinde Diazepamın Nitrik Oksit Sentaz ve Beyin Kaynaklı Nörotrofik Faktör Üzerine Etkisinin Araştırılması

Şahin

Güneş

2022

Türk Doğa Ve Fen Dergisi

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Bu çalışmanın amacı, sıçanlarda pentilentetrazol (PTZ) ile oluşturulan nöbetlerde diazepamın antikonvulzif etkinliğinde nitrik oksit sentaz (NOS) ve beyin kaynaklı nörotrofik faktör (BDNF) üzerine etkisini araştırmaktır. Çalışmada 24 adet erkek Wistar Albino sıçan kullanılmıştır. Sıçanlar kontrol grubu, salin (1 mL kg-1) + PTZ, diazepam (0,5 mg kg-1) + PTZ ve diazepam (2 mg kg-1)+PTZ grubu olarak 4 gruba ayrılmıştır (n=6). İntraperitoneal ilaç uygulamalarından 24 saat sonra biyokimyasal incelemeler için tüm sıçanların beyin dokuları çıkarılıp, korteks ve hipokampüs bölgeleri ayrılmıştır. Korteks ve hipokampüsteki NOS ve BDNF düzeyleri enzim bağlı immünosorbent analizi (ELISA) kitleri kullanılarak ölçülmüştür. Diazepam, salin+PTZ uygulanan grubuna göre istatistiksel açıdan anlamlı bir şekilde nöbet evresini azalttı ve ilk miyoklonik jerk (İMJ) süresini uzattı (p

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“…The latency, duration and intensity of each seizure were recorded, and the average values were calculated for statistical analysis. Seizure intensity scores were graded on the Racine scale [73] : Grade : generalized tonic-clonic seizures and falls; Grade : standing with forelimb clonus; Grade : forelimb clonus; Grade : rhythmic nodding; Grade : tremor, facial muscle twitching, chewing; Grade 0: no seizures. A -grade indicates successful seizure modeling.…”

Section: Establish Rat Epilepsy Modelmentioning

confidence: 99%

Genistein Protects Epilepsy-Induced Brain Injury Through Regulating The JAK2/STAT3 and Keap1/Nrf2 Signaling Pathways in The Developing Rats

Huang

Feng

et al. 2021

Preprint

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Background: Epilepsy is a common chronic neurological disease caused by the over-synchronization of neurons that lead to brain dysfunction. Recurrent seizures or status epilepticus can cause irreversible brain damage. The JAK2-STAT3 signal transduction pathway is stimulated by cytokines and involved in various pathological processes including inflammation, apoptosis and immune regulation in central system diseases. Keap1/Nrf2 is an important anti-oxidative stress pathway, which can reduce the toxic effects of oxygen free radicals and endogenous toxins on neurons. Genistein (Gen) can modulate inflammation and neuronal apoptosis, and may thereby have antiepileptic effects. This study aimed to explore the regulation of Genistein on JAK2/STAT3 and Keap1/Nrf2 signaling pathway and the protective effects on brain injury after epilepsy. Methods: Pentylenetetrazole (PTZ) was used to induce epilepsy in developing rats and Genistein was used for pretreatment of epilepsy. The seizure latency, grade scores and duration of the first generalized tonic-clonic seizure (GTCs) were recorded. Hippocampus tissue was sampled at 24 hours post-epilepsy. Immunofluorescence staining was used to observe the number of mature neurons, activated microglia and astrocytes in the hippocampal CA1 region. Western blot and qRT-PCR were used to determine the protein and mRNA levels of p-JAK2, p-STAT3, TNF-α, IL-1β, Keap1, Nrf2, HO-1, NQO1, caspase3, Bax and Bcl2 in the hippocampus. Results: Immunofluorescence showed that the number of neurons significantly decreased, and activated microglia and astrocytes significantly increased after epilepsy; Western blot and q-PCR showed that the expressions of p-JAK2, p-STAT3, TNF-α, IL-1β, Keap1, caspase3 and Bax significantly increased, while Nrf2, HO-1, NQO1 and Bcl-2 were significantly reduced after epilepsy. These effects were reversed by Genistein treatment. Moreover, Genistein was found to prolong seizure latency and reduce seizure intensity score and duration of generalized tonic-clonic seizures(GTCs). Conclusions: Genistein can activate the Keap1/Nrf2 antioxidant stress pathway and attenuate the activation of microglia and astrocytes. Genistein also inhibits the JAK2-STAT3 inflammation pathway and expression of apoptotic proteins, and increases the number of surviving neurons, thus having a protective effect on epilepsy-induced brain damage.

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Transcranial direct current stimulation (tDCS) affects neuroinflammation parameters and behavioral seizure activity in pentylenetetrazole-induced kindling in rats

Cited by 18 publications

References 79 publications

Transcranial current stimulation in epilepsy: A systematic review of the fundamental and clinical aspects

Transcranial current stimulation in epilepsy: A systematic review of the fundamental and clinical aspects

Pentilentetrazol ile Oluşturulan Akut Nöbet Modelinde Diazepamın Nitrik Oksit Sentaz ve Beyin Kaynaklı Nörotrofik Faktör Üzerine Etkisinin Araştırılması

Genistein Protects Epilepsy-Induced Brain Injury Through Regulating The JAK2/STAT3 and Keap1/Nrf2 Signaling Pathways in The Developing Rats

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