Neuropathological profile of the pentylenetetrazol (PTZ) kindling model

Samokhina, Evgeniia; Samokhin, A. N.

doi:10.1080/00207454.2018.1481064

Cited by 81 publications

(75 citation statements)

References 97 publications

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“…suggested that compared with the PTZ model, different brain regions exhibit specific electrophysiological profiles in the Lithium-Pilocarpine model, which might reflect their respective roles in the occurrence and development of seizures and SE. It has been reported that the hippocampal area is more likely involved in high-stage seizures, such as clonic or tonic-clonic seizures (Szyndler et al, 2009;Samokhina and Samokhin, 2018). The hippocampus has a relatively low epileptogenic threshold, which might explain the robust EEG response in CA3 and DG compared with that observed in the other brain areas.…”

Section: Eeg Changes In Different Brain Regions In Response To Se Indmentioning

confidence: 99%

Neural Activities in Multiple Rat Brain Regions in Lithium-Pilocarpine-Induced Status Epilepticus Model

Fan

Shan

Yang

et al. 2020

Front. Mol. Neurosci.

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To clarify the different regional brain electroencephalogram (EEG) activities and biochemical responses in seizure and epilepsy models, we assessed the EEG and c-Fos immunolabeling characteristics in a lithium-pilocarpine-induced status epilepticus (SE) model and pentylenetetrazol (PTZ)-induced seizure model. The regional brain activities were evaluated by EEG and c-Fos immunolabeling. ZnT3 immunostaining was performed to observe hippocampal mossy fiber sprouting (MFS) within 7 days after the induction of SE in the lithium-pilocarpine model. The EEG recordings showed distinctive features of activation in different brain areas. With the aggravation of the behavioral manifestations of the seizures, the frequency and amplitude of the discharges on EEG gradually increased. SE was eventually induced and sustained. The labeling of c-Fos was enhanced in the cortex and hippocampal CA1, CA3, and dentate gyrus (DG); however, compared to the PTZ-induced seizure model, c-Fos staining could only be observed in the striatum and thalamus in the lithium-pilocarpine-induced epilepsy model. In each brain region, prominent c-Fos labeling was observed 2 h and 4 h after the induction of SE or seizures and diminished at 24 h. During the lithium-pilocarpineinduced chronic epilepsy phase after SE induction, MFS was observed 7 days after SE and was accompanied by the dynamic evolution of epileptic EEG activities. These findings validated the lithium-pilocarpine-induced SE model as an epilepsy model with a specific spatial-temporal profile of neural activation. The EEG characteristics and c-Fos expression patterns differ from those presented in a previous study using a PTZ-induced seizure model. Hippocampal mossy fiber spouting might be associated with spontaneous seizures during the chronic phase and can be detected at least within 1 week by ZnT3 staining after stimulation.

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Section: Eeg Changes In Different Brain Regions In Response To Se Indmentioning

confidence: 99%

Neural Activities in Multiple Rat Brain Regions in Lithium-Pilocarpine-Induced Status Epilepticus Model

Fan

Shan

Yang

et al. 2020

Front. Mol. Neurosci.

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“…It has been widely used to demonstrate stimulusinduced neuronal activation 33; 34 . Subconvulsive administration of PTZ (10-40 mg / kg) causes c-Fos immunoreactivity in the thalamus and hypothalamus regions of adult rats 35 . Similarly, in our study, c-Fos expression was significantly increased in PTZ group in DG, CA1, CA2 and CA3 areas.…”

Section: Discussionmentioning

confidence: 98%

Investigation of anti-epileptic mechanisms of 5HT1A receptor with pentylenetetrazole induced epilepsy model in rats

Şahin¹,

Özdemir

Taşkıran

et al. 2019

Cumhuriyet Medical Journal

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According to current neurophysiological evidence, the role of 5hydroxytryptamine (5-HT) receptors in epileptic seizure formation is still not fully elucidated. The aim of this study was to investigate the effects of 5-HT 1A receptor on epileptic seizure with pentylenetetrazole induced epilepsy in rats. Method: In this study, 28 male Wistar Albino rats weighing 240-260 g were used. Pentylenetetrazole (PTZ, 35 mg/kg, i.p.) was injected to the rats to induce epilepsy, and seizure stages were determined according to the Racine scale. Electrodes were placed in the skulls of the animals under stereotaxis for ECoG recording. All the experimental animals were sacrificed by decapitation after ECoG and video recordings. GABA level was measured using the Elisa kit from brain tissues, and c-Fos expression was shown immunohistochemically. Results: According to the results, it was shown that 8-OH-DPAT increased the time of the initial myoclonic jerk (FMJ (p<0.05). However, the number of epileptic spikes was reduced by 8-OH-DPAT (p<0.05). GABA levels decreased in PTZ group (p<0.05). 8-OH-DPAT and WAY-100135 decreased c-Fos expression in all hippocampal areas (p<0.05). Conclusions: In conclusion, 5-HT 1A receptor agonist 8-OH-DPAT, showed an anti-epileptic effect. The anti-epileptic effects of 5-HT 1A receptor were found to be inconsistent with changes in GABA level. the c-Fos expression is a marker of neuronal activation and may be related to the anti-convulsive effect of 5-HT 1A receptor.

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“…Therefore, drugs effective in PTZinduced seizure models are generally considered to act via GABAergic mechanisms. Kindling induced by PTZ was shown to produce not only changes in the GABA-mediated neurotransmission but also various alterations in glutamate excitatory neurotransmission, mediated by both NMDA and AMPA receptors, as well as some morphological changes in the hippocampus, glucose hypometabolism, or antioxidant defense systems [50,51]. Noteworthy, a crucial role of synaptic vesicle glycoprotein 2A (SV2A) in kindling development has been also postulated [52].…”

Section: Discussionmentioning

confidence: 99%

N-Benzyl-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) with Hybrid Structure as a Candidate for a Broad-Spectrum Antiepileptic Drug

et al. 2020

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In our recent studies, we identified compound N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) as a broad-spectrum hybrid anticonvulsant which showed potent protection across the most important animal acute seizure models such as the maximal electroshock (MES) test, the subcutaneous pentylenetetrazole (s.c. PTZ) test, and the 6-Hz (32 mA) test in mice. Therefore, AS-1 may be recognized as a candidate for new anticonvulsant effective in different types of human epilepsy with a favorable safety margin profile determined in the rotarod test in mice. In the aim of further pharmacological evaluation of AS-1, in the current study, we examined its activity in the 6-Hz (44 mA) test, which is known as the model of drug-resistant epilepsy. Furthermore, we determined also the antiseizure activity in the kindling model of epilepsy induced by repeated injection of pentylenetetrazole (PTZ) in mice. As a result, AS-1 revealed relatively potent protection in the 6-Hz (44 mA) test, as well as delayed the progression of kindling induced by repeated injection of PTZ in mice at doses of 15 mg/kg, 30 mg/kg, and 60 mg/kg. Importantly, the isobolographic analysis showed that a combination of AS-1 and valproic acid (VPA) at the fixed ratio of 1:1 displayed a supra-additive (synergistic) interaction against PTZinduced seizures in mice. Thus, AS-1 may be potentially used in an add-on therapy with VPA. Moreover, incubation of zebrafish larvae with AS-1 substantially decreased the number, cumulative but not the mean duration of epileptiform-like events in electroencephalographic assay. Finally, the in vitro ADME-Tox studies revealed that AS-1 is characterized by a very good permeability in the parallel artificial membrane permeability assay test, excellent metabolic stability on human liver microsomes (HLMs), no significant influence on CYP3A4/CYP2D6 activity, and moderate inhibition of CYP2C9 in a concentration of 10 μM, as well as no hepatotoxic properties in HepG2 cells (concentration of 10 μM).

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Neuropathological profile of the pentylenetetrazol (PTZ) kindling model

Abstract: PTZ kindling model may improve understanding of the seizures development provided that the differences existing between the phases of kindling model are taken into account.

Cited by 81 publications

References 97 publications

Neural Activities in Multiple Rat Brain Regions in Lithium-Pilocarpine-Induced Status Epilepticus Model

Neural Activities in Multiple Rat Brain Regions in Lithium-Pilocarpine-Induced Status Epilepticus Model

Investigation of anti-epileptic mechanisms of 5HT1A receptor with pentylenetetrazole induced epilepsy model in rats

N-Benzyl-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) with Hybrid Structure as a Candidate for a Broad-Spectrum Antiepileptic Drug

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