PTZ kindling model for epileptogenesis, refractory epilepsy, and associated comorbidities: relevance and reliability

2021 ◽  
Vol 36 (7) ◽  
pp. 1573-1590
Author(s):  
Tanveer Singh ◽  
Awanish Mishra ◽  
Rajesh Kumar Goel
Keyword(s):  
Refractory Epilepsy ◽  
Kindling Model ◽  
Ptz Kindling ◽  
Relevance And Reliability

Neuroprotective mechanisms of sildenafil and selenium in PTZ-kindling model: Implications in epilepsy

2018 ◽  
Vol 833 ◽  
pp. 131-144 ◽  
Author(s):  
Karim M. Tawfik ◽  
Yasser M. Moustafa ◽  
Mona F. El-Azab
Keyword(s):  
Kindling Model ◽  
Ptz Kindling

Comparative studies on the effects of clinically used anticonvulsants on the oxidative stress biomarkers in pentylenetetrazole-induced kindling model of epileptogenesis in mice

2017 ◽  
Vol 28 (1) ◽  
Author(s):  
Faizan Mazhar ◽  
Saima M. Malhi ◽  
Shabana U. Simjee
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Protein Carbonyl ◽  
Anticonvulsant Effect ◽  
Oxidative Stress Biomarkers ◽  
Kindling Model ◽  
Stress Biomarkers ◽  
Ptz Kindling ◽  
Oxide Synthase

AbstractBackground:Oxidative stress plays a key role in the pathogenesis of epilepsy and contributes in underlying epileptogenesis process. Anticonvulsant drugs targeting the oxidative stress domain of epileptogenesis may provide better control of seizure. The present study was carried out to investigate the effect of clinically used anti-epileptic drugs (AEDs) on the course of pentylenetetrazole (PTZ)-induced kindling and oxidative stress markers in mice.Methods:Six mechanistically heterogeneous anticonvulsants: phenobarbital, phenytoin, levetiracetam, pregabalin, topiramate, and felbamate were selected and their redox profiles were determined. Diazepam was used as a drug control for comparison. Kindling was induced by repeated injections of a sub-convulsive dose of PTZ (50 mg/kg, s.c.) on alternate days until seizure score 5 was evoked in the control kindled group. Anticonvulsants were administered daily. Following PTZ kindling, oxidative stress biomarkers were assessed in homogenized whole brain samples and estimated for the levels of nitric oxide, peroxide, malondialdehyde, protein carbonyl, reduced glutathione, and activities of nitric oxide synthase and superoxide dismutase.Results:Biochemical analysis revealed a significant increase in the levels of reactive oxygen species with a parallel decrease in endogenous anti-oxidants in PTZ-kindled control animals. Daily treatment with levetiracetam and felbamate significantly decreased the PTZ-induced seizure score as well as the levels of nitric oxide (p<0.001), nitric oxide synthase activity (p<0.05), peroxide levels (p<0.05), and malondialdehyde (p<0.05). Levetiracetam and felbamate significantly decreased lipid and protein peroxidation whereas topiramate was found to reduce lipid peroxidation only.Conclusions:An AED that produces anticonvulsant effect by the diversified mechanism of action such as levetiracetam, felbamate, and topiramate exhibited superior anti-oxidative stress activity in addition to their anticonvulsant activity.

Proconvulsant effects of estriol, the third estrogen, in the mouse PTZ-kindling model

2014 ◽  
Vol 35 (10) ◽  
pp. 1561-1566 ◽  
Author(s):  
Aakifa Ahmad ◽  
Divya Vohora
Keyword(s):  
Kindling Model ◽  
The Third ◽  
Ptz Kindling

scholarly journals Expression of HIF-1α, TFRC-1 and TIM-2 Relative mRNA Levels in PTZ-Kindling Model of Epilepsy

2020 ◽  
Vol 12 (2) ◽  
pp. 947-954
Author(s):  
Hüseyin Emre DÜNDAR ◽  
Aslıhan ÖZTAŞ ◽  
Saliha Rabia ŞAHİN ◽  
Seher YİLMAZ ◽  
Furkan KOCABAŞ ◽  
...  
Keyword(s):  
Mrna Levels ◽  
Kindling Model ◽  
Ptz Kindling

scholarly journals Lacosamide Reduces Seizure Severity but Increases Seizure Frequency in PTZ-Kindled Rats

2017 ◽  
Vol 63 (4) ◽  
pp. 173-177
Author(s):  
Zsolt Gáll ◽  
Szabolcs Koncz ◽  
Orsolya Gáll ◽  
Melinda Kolcsár
Keyword(s):  
Behavioral Pattern ◽  
Anticonvulsant Action ◽  
Kindling Model ◽  
Generalized Seizures ◽  
Ptz Kindling ◽  
Male Wistar Rats ◽  
Generalized Epilepsy ◽  
Novel Drug ◽  
Saline Pretreatment ◽  
Different Doses

AbstractObjective: This study evaluated the anticonvulsant action of lacosamide (LCS), a novel drug that was recently approved for the treatment of partial or secondarily generalized seizures, using an animal model of generalized epilepsy induced by repetitive pentylenetetrazole (PTZ) administration in rats. The main goal was to evaluate the behavioral pattern of lacosamide action by classifying seizures according to a modi Racine-scale. Furthermore, the reproducibility of the win-PTZ kindling model of epilepsy, a recently described variant of the standard PTZ-kindling model, was also assessed.Methods: Adult male Wistar rats (n=16) were divided into two groups and underwent the win-PTZ-kindling protocol in two independent trials. After finishing the kindling procedure, all animals, which presented stage 5 seizures were tested for the anticonvulsant action of lacosamide at three different doses (3, 10, and 30 mg/kg).Results: The maximal severity of seizures decreased and the latency to stage 3-5 seizures increased when the animals were treated with lacosamide at a single dose of 10 mg/kg compared to saline pretreatment (p < 0.05), both parameter reflecting an anticonvulsant action of the drug. Unfortunately, the number of stage 3-5 seizures also increased, but not significantly. The win-PTZ kindling model showed an adequate reproducibility between different trials, however, the number of fully kindled rats was lower than previously reported.Conclusions: Lacosamide showed a convincing anticonvulsant action in the win-PTZ kindling model of epilepsy by preventing the generalization of seizures. The win-PTZ kindling model was proved to be useful for studying epileptogenesis and the anticonvulsant action of drugs.

scholarly journals Increased ACh-Associated Immunoreactivity in Autonomic Centers in PTZ Kindling Model of Epilepsy

Biomedicines ◽  
2020 ◽  
Vol 8 (5) ◽  
pp. 113 ◽  
Author(s):  
Enes Akyüz ◽  
Züleyha Doğanyiğit ◽  
Yam Nath Paudel ◽  
Emin Kaymak ◽  
Seher Yilmaz ◽  
...  
Keyword(s):  
Ion Channel ◽  
Resting Membrane Potential ◽  
Cardiac Pathology ◽  
Kindling Model ◽  
Cell Excitability ◽  
Ptz Kindling ◽  
Targeted Expression ◽  
Inwardly Rectifying ◽  
Histological Staining

Experimental and clinical studies of cardiac pathology associated with epilepsy have demonstrated an impact on the autonomic nervous system (ANS). However, the underlying molecular mechanism has not been fully elucidated. Molecular investigation of the neurotransmitters related receptor and ion channel directing ANS might help in understanding the associated mechanism. In this paper, we investigated the role of acetylcholine (ACh), which demonstrates both sympathetic and parasympathetic roles in targeted expression in terms of the relevant receptor and ion channel. Inwardly rectifying potassium (Kir) channels play a significant role in maintaining the resting membrane potential and controlling cell excitability and are prominently expressed in both the excitable and non-excitable tissues. The immunoreactivity of ACh-activated Kir3.1 channel and muscarinic ACh receptors (M2) in autonomic centers such as the brainstem, vagus nerve (VN) and atria of heart was confirmed by both histological staining and pathological tissue analysis. Significant upregulations of Kir3.1 and M2 receptors were observed in pentylenetetrazol (PTZ)-kindled epileptic rats for all related tissues investigated, whereas no pathological difference was observed. These findings provide proof-of-concept that changes in ACh-associated immunoreactivity might be linked to the ANS dysfunctions associated with epilepsy.

scholarly journals Alteration of Extracellular Matrix Molecules and Perineuronal Nets in the Hippocampus of Pentylenetetrazol-Kindled Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Hiroshi Ueno ◽  
Shunsuke Suemitsu ◽  
Shinji Murakami ◽  
Naoya Kitamura ◽  
Kenta Wani ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Synaptic Plasticity ◽  
Neural Circuit ◽  
Perineuronal Nets ◽  
Cellular Mechanisms ◽  
Kindling Model ◽  
Ptz Kindling ◽  
Extracellular Matrix Molecules ◽  
Model Mouse ◽  
Wisteria Floribunda

The pathophysiological processes leading to epilepsy are poorly understood. Understanding the molecular and cellular mechanisms involved in the onset of epilepsy is crucial for drug development. Epileptogenicity is thought to be associated with changes in synaptic plasticity; however, whether extracellular matrix molecules—known regulators of synaptic plasticity—are altered during epileptogenesis is unknown. To test this, we used a pentylenetetrazole- (PTZ-) kindling model mouse to investigate changes to hippocampal parvalbumin- (PV-) positive neurons, extracellular matrix molecules, and perineuronal nets (PNNs) after the last kindled seizure. We found an increase in Wisteria floribunda agglutinin- (WFA-) and Cat-315-positive PNNs and a decrease in PV-positive neurons not surrounded by PNNs, in the hippocampus of PTZ-kindled mice compared to control mice. Furthermore, the expression of WFA- and Cat-315-positive molecules increased in the extracellular space of PTZ-kindled mice. In addition, consistent with previous studies, astrocytes were activated in PTZ-kindled mice. We propose that the increase in PNNs after kindling decreases neuroplasticity in the hippocampus and helps maintain the neural circuit for recurrent seizures. This study shows that possibility of changes in extracellular matrix molecules due to astrocyte activation is associated with epilepticus in PTZ-kindled mice.

Neuropathological profile of the pentylenetetrazol (PTZ) kindling model

2018 ◽  
Vol 128 (11) ◽  
pp. 1086-1096 ◽  
Author(s):  
E. Samokhina ◽  
Alexander Samokhin
Keyword(s):  
Kindling Model ◽  
Ptz Kindling

Extraction, GC-MS evaluation and anti-epileptic potential of seeds ethanolic extract of Putranjiva roxburghii Wall

2020 ◽  
Vol 20 ◽  
Author(s):  
Chandra Kala ◽  
Syed Sarim Imam ◽  
Mohamad Taleuzzaman ◽  
Sadaf Jamal Gilani ◽  
Syed Salman Ali ◽  
...  
Keyword(s):  
Ethanolic Extract ◽  
Experimental Models ◽  
Biologically Active ◽  
Maximal Electroshock ◽  
Oral Toxicity ◽  
Kindling Model ◽  
Ms Analysis ◽  
Ptz Kindling ◽  
Putranjiva Roxburghii ◽  
Dose Dependent

Background: Putranjiva roxburghii Wall is traditionally known to cure many pathological conditions including epilepsy. Objective: The present study is aimed at determining bioactive compounds in ethanolic extract of Putranjiva roxburghii test extract (PRTE) seeds by GCMS analysis and to assess its anti-epileptic potential using various experimental models of epilepsy. Methods: The ethanolic extract of seeds of Putranjiva roxburghiiwas subjected to GC-MS analysis to detect the bioactive phytoconstituents. Acute oral toxicity of the extract was performed using OCED guideline 420. Pentylenetetrazol (PTZ) kindling model of epilepsy and Maximal electroshock epilepsy (MES) model of epilepsy were used to determine antiepileptic potential. Results: The GC-MS analysis of the extract revealed the presence of 20 phytoconstituents. The major phytoconstituents included n-Propyl heptyl ether (25.25%), 5-Ethyl hydantoin (8%), octadec-9-enoic acid (16-25%) and 1, 2-Benzene dicarboxylic acid (11.86%). The PRTE (50 mg/kg and 100 mg/kg) afforded significant and dose - dependent protection against PTZ – induced kindling epilepsy and MES induced epilepsy (p<0.001 and p<0.01). Conclusion: Based on the above finding, it is evident that Putranjiva roxburghii seeds contain biologically active compound. It can also be concluded that the extract possesses anti-epileptic potential.

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