Combined blockade of AMPA and NMDA receptors in the brain of rats prevents pentylenetetrazole-induced clonic and tonic-clonic seizures without ataxia

Гмиро, В. Е.; Serdyuk, S. E.

doi:10.1007/s10517-008-0194-3

Cited by 18 publications

(6 citation statements)

References 13 publications

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“…AMPA receptors are of primary importance in initiating seizures because inhibition of AMPA receptors is more effective than inhibition of NMDA receptors in abolishing epileptiform discharges (Hwa and Avoli, 1991; Hwa et al, 1991; Jones and Lambert, 1990; Nakamura et al, 1995; Williamson and Wheal, 1992). Combination of antiepileptic drugs targeting AMPA and NMDA receptors has been shown to prevent seizures in pentylenetetrazole-treated rats (Gmiro and Serdyuk, 2008). Immunoreactivity of AMPA and NMDA receptors subunits has been found to be increased in the hippocampus of TLE patients (Mathern et al, 1998).…”

Section: The Glutamate/gaba Hypothesis: Enhancement Of Excitation mentioning

confidence: 99%

Physiological bases of the K+ and the glutamate/GABA hypotheses of epilepsy

et al. 2014

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Epilepsy is a heterogeneous family of neurological disorders that manifest as seizures, i.e. the hypersynchronous activity of large population of neurons. About 30% of epileptic patients do not respond to currently available antiepileptic drugs. Decades of intense research have elucidated the involvement of a number of possible signaling pathways, however, at present we do not have a fundamental understanding of epileptogenesis. In this paper, we review the literature on epilepsy under a wide-angle perspective, a mandatory choice that responds to the recurrent and unanswered question about what is epiphenomenal and what is causal to the disease. While focusing on the involvement of K+ and glutamate/GABA in determining neuronal hyperexcitability, emphasis is given to astrocytic contribution to epileptogenesis, and especially to loss-of-function of astrocytic glutamine synthetase following reactive astrogliosis, a hallmark of epileptic syndromes. We finally introduce the potential involvement of abnormal glycogen synthesis induced by excess glutamate in increasing susceptibility to seizures.

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Section: The Glutamate/gaba Hypothesis: Enhancement Of Excitation mentioning

confidence: 99%

Physiological bases of the K+ and the glutamate/GABA hypotheses of epilepsy

et al. 2014

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“…We conducted experiments in the presence of three different channel blockers, including N , N , N -trimethyl-5-[(tricyclo[3.3.1.13,7]dec-1-ylmethyl)amino]-1-pentanaminium bromide hydrobromide (IEM-1460) (Magazanik et al, 1997), the Joro spider toxin analogue 1-naphthyl acetyl spermine (NASPM) (Koike et al, 1997; Takazawa et al, 1996), and AgTx-636 (Grishin et al, 1989; Herlitze et al, 1993), which we extracted and purified from the orb weaver spider Argiope lobataitalic . These channel blockers show promise for treating CP-AMPAR-related conditions; IEM-1460 (μM potency) attenuates epileptic seizure (Gmiro and Serdyuk, 2008; Szczurowska and Mares, 2015), may reduce visceral pain (Kopach et al, 2016; Liu et al, 2015) and CP-AMPAR activity related to schizophrenia (Umino et al, 2018); NASPM (sub-μM potency) reduces oxidative stress and protects neurons following ischemia (Noh et al, 2005; Zhang et al, 2003); AgTx-636 (nM potency) is an efficacious natural CP-AMPAR channel blocker with neuroprotective properties (Barygin et al, 2011; Green et al, 1996; Poulsen et al, 2013). We determine the molecular composition of the blocker binding site in AMPAR complexes, identify how different blocker moieties contribute to its inhibitory action and how the blockers can be trapped inside the ion channel.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Channel Block in Calcium-Permeable AMPA Receptors

Twomey

Yelshanskaya

Vassilevski

et al. 2018

Neuron

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AMPA receptors mediate fast excitatory neurotransmission and are critical for CNS development and function. Calcium-permeable subsets of AMPA receptors are strongly implicated in acute and chronic neurological disorders. However, despite the clinical importance, the therapeutic landscape for specifically targeting them, and not the calcium-impermeable AMPA receptors, remains largely undeveloped. To address this problem, we used cryo-electron microscopy and electrophysiology to investigate the mechanisms by which small-molecule blockers selectively inhibit ion channel conductance in calcium-permeable AMPA receptors. We determined the structures of calcium-permeable GluA2 AMPA receptor complexes with the auxiliary subunit stargazin bound to channel blockers, including the orb weaver spider toxin AgTx-636, the spider toxin analog NASPM, and the adamantane derivative IEM-1460. Our structures provide insights into the architecture of the blocker binding site and the mechanism of trapping, which are critical for development of small molecules that specifically target calcium-permeable AMPA receptors.

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“…It is well-documented that increased intracellular Ca 2+ concentration plays a significant role in epileptic activity [2223], leading to neuronal death in SE [24]. Glutamate receptors are likely involved in modulating susceptibility to seizure development [2526]. Furthermore, lithium attenuates NMDA-mediated Ca 2+ influx into neurons [27].…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effect of lithium after pilocarpine-induced status epilepticus in mice

Hong

Choi

Kim

et al. 2017

Korean J Physiol Pharmacol

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Status epilepticus is the most common serious neurological condition triggered by abnormal electrical activity, leading to severe and widespread cell loss in the brain. Lithium has been one of the main drugs used for the treatment of bipolar disorder for decades, and its anticonvulsant and neuroprotective properties have been described in several neurological disease models. However, the therapeutic mechanisms underlying lithium's actions remain poorly understood. The muscarinic receptor agonist pilocarpine is used to induce status epilepticus, which is followed by hippocampal damage. The present study was designed to investigate the effects of lithium post-treatment on seizure susceptibility and hippocampal neuropathological changes following pilocarpine-induced status epilepticus. Status epilepticus was induced by administration of pilocarpine hydrochloride (320 mg/kg, i.p.) in C57BL/6 mice at 8 weeks of age. Lithium (80 mg/kg, i.p.) was administered 15 minutes after the pilocarpine injection. After the lithium injection, status epilepticus onset time and mortality were recorded. Lithium significantly delayed the onset time of status epilepticus and reduced mortality compared to the vehicle-treated group. Moreover, lithium effectively blocked pilocarpine-induced neuronal death in the hippocampus as estimated by cresyl violet and Fluoro-Jade B staining. However, lithium did not reduce glial activation following pilocarpine-induced status epilepticus. These results suggest that lithium has a neuroprotective effect and would be useful in the treatment of neurological disorders, in particular status epilepticus.

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Combined blockade of AMPA and NMDA receptors in the brain of rats prevents pentylenetetrazole-induced clonic and tonic-clonic seizures without ataxia

Cited by 18 publications

References 13 publications

Physiological bases of the K+ and the glutamate/GABA hypotheses of epilepsy

Physiological bases of the K+ and the glutamate/GABA hypotheses of epilepsy

Mechanisms of Channel Block in Calcium-Permeable AMPA Receptors

Neuroprotective effect of lithium after pilocarpine-induced status epilepticus in mice

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