The Effects of Adenosinergic Modulation on Cytokine Levels in a Pentylenetetrazole-Induced Generalized Tonic-Clonic Seizure Model

Dede, Fazilet; Karadenizli, Sabriye; Özsoy, Özgür Doğa; Eraldemir, Fatma Ceyla; Şahin, Deniz; Ateş, Nurbay

doi:10.1159/000478659

Cited by 10 publications

(4 citation statements)

References 33 publications

(32 reference statements)

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“…Numerous in ammatory mediators, including soluble polypeptides known as cytokines, play a crucial role in both the activation of innate immunity and the transition to adaptive immunity. Ils and TNFs are two of these molecules (40).Through previous studies, it was concluded that PTZ increased the level of in ammatory cytokines such as TNF-α and IL-1β in the brain via activation of microglia and astrocytes (39) (41). Our ndings were consistent with previous research.…”

Section: Discussionsupporting

confidence: 90%

Ursolic acid along with Caprylic acid Ameliorates Pentylenetetrazole Induced Seizures Like Behavior in Adult Zebrafish

Sharma

Kaur

Kapil

et al. 2022

Preprint

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Background: Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures. Despite the existence of more than 20 anti-epileptic drugs there is still a need for new treatments which could not only treat symptoms but also cure epileptogenesis. PTZ is a Chemoconvulsant that impair GABAergic and glutamatergic neurotransmission, promoting excitotoxicity and seizures. Therefore PTZ exposure has been considered a suitable protocol to assess seizure-like behaviours. UA is a triterpenoid compound having anti-inflammatory, anti-oxidant and neuro protective action. CA is one of the component of ketogenic diet and it supresses the inflammation. Objective: The objective of the present study was to investigate the effect of combination therapy of UA and CA on seizures, neuronal damage and inflammation induced by PTZ in adult zebrafish.Materials and method: Zebrafishes were pretreated with Diazepam (1.25 mg/kg), UA(50 and 150 mg/kg), CA (60 mg/kg) and combination of UA (50 mg/kg) and CA (60 mg/kg) followed by PTZ (170 mg/kg) i.p administration. Various neurobehavioral, biochemical parameters like lipid peroxidase (LPO), catalase, superoxide dismutase, glutathione-s-transferase (GSH) and acetylcholinesterase (AChEs), molecular parameters such as TNF-α, IL-10, Nrf-2 and IL-1β and mitochondrial parameters like complex I, II, IV and MTT assay, histopathological study were performed to determine the effect of therapy.Result: UA of both doses and CA decreased mean seizure score, mean seizure time . Importantly, combination of UA 50 mg/kg and CA 60 mg/kg attenuated seizure-like behavioral scores, decreased mean seizure time, mean seizure score and reduced the frequency of clonic-like seizures (score 4). Combination of UA 50 mg/kg and CA 60 mg/kg also prevented oxidative stress in PTZ-challenged fish by decreasing lipid peroxidation, acetyl cholinesterase activity and increasing catalase, glutathione-s-transferase and superoxide dismutase levels. Additionally, the combination therapy prevented inflammatory response by declining TNF-α and IL-1β levels and raising IL-10 and Nrf-2 levels. Moreover combination of UA 50 mg/kg and CA 60 mg/kg significantly improved mitochondrial complex I, II and IV activity as well as increase MTT assay. Furthermore, morphology of neuronal cell was prevented in combination of UA 50 mg/kg and CA 60 mg/kg when seen in histopathology. Similarly as observed in DZP group, combination of UA 50 mg/kg and CA 60 mg/kg affect the overall swimming activity of fish, suggesting different mechanisms of action. Collectively, we show that combination of UA 50 mg/kg and CA 60 mg/kg attenuates PTZ-induced seizure-like behaviours, brain oxidative stress, mitochondrial and morphological damage of neuronal cell in zebrafish, suggesting the involvement of antioxidant mechanisms in neuroprotection.Conclusion: The present study shows that combination of UA 50 mg/kg and CA 60 mg/kg ameliorates the seizures completely and have neuroprotective action via their anti-inflammatory, anti-oxidant properties.

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Section: Discussionsupporting

confidence: 90%

Ursolic acid along with Caprylic acid Ameliorates Pentylenetetrazole Induced Seizures Like Behavior in Adult Zebrafish

Sharma

Kaur

Kapil

et al. 2022

Preprint

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“…In this study, we show that there is increase in IL-1β levels chronic PTZ models in the cortex (Figure 2 Show that IL-1β may be associated with the both epileptic seizure and epileptogenesis. Our findings of IL-1β levels in acute and chronic PTZ models is consistent one of the previous studies which are carried out in rat and mice brain [15,20,23]. According to our findings, it may be suggested that TNF-α is assotiated with epileptogenesis, while IL-1β is related to both acute seizure and epileprogenesis.…”

Section: Proinflammatory Cytokines In Acute and Chronic Ptz Modelssupporting

confidence: 92%

“…These findings show that TNF-α raises after epileptogenesis and is not related to acute epileptic seizures. Our findings of TNF-α levels in acute PTZ model is coherent one of the previous study [15]. On the other hand, some studies have shown the increase in TNF-α levels after a single PTZ induced seizures dose in total brain and serum in contrast to our study [16,17].…”

Section: Proinflammatory Cytokines In Acute and Chronic Ptz Modelssupporting

confidence: 91%

The comparison of inflammatory markers in pentylenetetrazole-induced acute epileptic seizure model and chronic epilepsy model in rats

Taşkıran

Taştemur

2020

Cumhuriyet Science Journal

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Recent studies have provided important evidence that neuroinflammation has an effective role in epilepsy pathophysiology. However, it is not clear that the occurrence of neuroinflammation is related to one epileptic seizure or repeating seizures. Therefore, we aimed to investigate the comparison of inflammatory markers in pentylenetetrazole-induced acute epileptic seizure model and chronic epilepsy model in rats. In this study, 18 male Wistar albino rats were used. The animals divided into three groups as control, acute epileptic seizure model and chronic epilepsy model. Inflammatory markers (TNF-α, IL-1 β, COX-1, and COX-2) were measured by using ELISA methods in the cortical and hippocampal brain regions after completing the epileptic model procedure. Statistical evaluation of the data was performed by one-way ANOVA and multiple comparisons were determined by the Tukey test. Statistical significance was defined at p<0.05. Obtained data show that there was significant increase in inflamattory markers in chronic epilepsy model compared to the control and acute epileptic seizure model (p<0.05). In conlusion, this study may suggest that inflammatory sytem is related to epileptogenesis process rather than only one epileptic seizure.

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“…Elevated levels of proinflammatory cytokines have been identified in the CSF of patients with refractory SE (Wang & Chen, 2018). Generalized seizure pathogenesis has also been associated with cytokines -TNF-a, IL-1B and IL-6 (Dede et al, 2017). The increased cytokine levels suggested in COVID-19 may explain the high incidence of status epilepticus and generalized seizures in COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological management of seizures in patients with COVID-19: a systematic review

et al. 2021

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Background: Some patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported to exhibit neurological symptoms such as seizures and impaired consciousness. Our study reviews reported cases to assess the pharmacological approach to managing seizures in SARS-CoV-2 patients and associated outcomes. Methods: A systematic review of case reports on the incidence of seizures following coronavirus disease 2019 (COVID-19) among patients that reported use of antiepileptic drugs (AEDs) in management was performed by using the PRISMA (preferred reporting items for systematic reviews and meta-analysis) guidelines. Databases used included EMBASE, PubMed, SCOPUS, and Google Scholar. Data was presented as qualitative and descriptive data. Results: In total, 67 articles were selected for full-text assessment, of which 19 were included in the final review. Patients had a median age of 54 years, most of whom were male. Remdisivir, dexamethasone, Laminavir, hydroxychloroquine, azithromycin, and Lopinavir-ritonavir were common agents used in the management of COVID-19. Most patients presented with either generalized tonic-clonic seizures or status epilepticus. Most patients received levetiracetam as drug choice or as part of their regimen. Other AEDs commonly prescribed included midazolam and sodium valproate. Some patients received no antiepileptic drug therapy. Most of the patients who died had more than one comorbidity. Also, most of the patients who died received COVID-19 treatment drugs. None of the patients who received midazolam as drug choice or as part of their regimen developed recurrent seizures in contrast to patients who received levetiracetam and sodium valproate as drug choice or as part of their regimen. Interestingly, none of the patients who received no AEDs suffered recurrent seizures or died. Conclusions: Standard guidelines for managing seizures in COVID-19 patients may be required. A limitation of this review is that it involved the use of case reports with no controls and a small number of patients.

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The Effects of Adenosinergic Modulation on Cytokine Levels in a Pentylenetetrazole-Induced Generalized Tonic-Clonic Seizure Model

Cited by 10 publications

References 33 publications

Ursolic acid along with Caprylic acid Ameliorates Pentylenetetrazole Induced Seizures Like Behavior in Adult Zebrafish

Ursolic acid along with Caprylic acid Ameliorates Pentylenetetrazole Induced Seizures Like Behavior in Adult Zebrafish

The comparison of inflammatory markers in pentylenetetrazole-induced acute epileptic seizure model and chronic epilepsy model in rats

Pharmacological management of seizures in patients with COVID-19: a systematic review

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