Memantine attenuates cognitive impairments after status epilepticus induced in a lithium–pilocarpine model

Kalemenev, S. V.; Зубарева, О. Е.; Sizov, V. V.; Lavrent’eva, V. V.; Lukomskaya, N. Ya.; Kim, K. Kh.; Zaitsev, Aleksey V.; Magazanik, L. G.

doi:10.1134/s0012496616050148

Cited by 8 publications

(5 citation statements)

References 14 publications

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“…In this study, memantine did provide significant reductions in FJB compared to controls in all brain regions. This is consistent with previous reports of memantine's ability to protect against OPNA and SE-related brain damage and cognitive deficits (Jia, et al, 2011;Kalemenev, et al, 2016;Zaja-Milatovic, Gupta, Aschner, & Milatovic, 2009;Zenki, et al, 2018). This suggests that FJB quantification can be used in our model to identify a drug that is neuroprotective without necessitating concurrent anticonvulsant efficacy.…”

Section: Discussionsupporting

confidence: 92%

Validating a model of benzodiazepine refractory nerve agent-induced status epilepticus by evaluating the anticonvulsant and neuroprotective effects of scopolamine, memantine, and phenobarbital

Jackson

Ardinger

Winter

et al. 2019

Journal of Pharmacological and Toxicological Methods

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Introduction: Organophosphorus nerve agents (OPNAs) irreversibly block acetylcholinesterase activity, resulting in accumulation of excess acetylcholine at neural synapses, which can lead to a state of prolonged seizures known as status epilepticus (SE). Benzodiazepines, the current standard of care for SE, become less effective as latency to treatment increases. In a mass civilian OPNA exposure, concurrent trauma and limited resources would likely cause a delay in first response time. To address this issue, we have developed a rat model to test novel anticonvulsant/ neuroprotectant adjuncts at delayed time points. Methods: For model development, adult male rats with cortical electroencephalographic (EEG) electrodes were exposed to soman and administered saline along with atropine, 2-PAM, and midazolam 5, 20, or 40 minutes after SE onset. We validated our model using three drugs: scopolamine, memantine, and phenobarbital. Using the same procedure outlined above, rats were given atropine, 2-PAM, midazolam and test treatment 20 minutes after SE onset. Results: Using gamma power, delta power, and spike rate to quantify EEG activity, we found that scopolamine was effective, memantine was minimally effective, and phenobarbital had a delayed effect on terminating SE. Fluoro-Jade B staining was used to assess neuroprotection in *

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Section: Discussionsupporting

confidence: 92%

Validating a model of benzodiazepine refractory nerve agent-induced status epilepticus by evaluating the anticonvulsant and neuroprotective effects of scopolamine, memantine, and phenobarbital

Jackson

Ardinger

Winter

et al. 2019

Journal of Pharmacological and Toxicological Methods

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“…Memantine has demonstrated the potential to prevent cognitive deficits in numerous animal seizure models and appears to have a considerable neuroprotective effect against glutamate and NMDA neurotoxicity [ 112 , 113 ]. Memantine appears to diminish neurotoxicity in pilocarpine-induced SE and convulsion duration in pentylenetetrazole (PTZ) models [ 113 , 114 ].…”

Section: Sementioning

confidence: 99%

The Roles of Glutamate Receptors and Their Antagonists in Status Epilepticus, Refractory Status Epilepticus, and Super-Refractory Status Epilepticus

et al. 2023

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Status epilepticus (SE) is a neurological emergency with a high mortality rate. When compared to chronic epilepsy, it is distinguished by the durability of seizures and frequent resistance to benzodiazepine (BZD). The Receptor Trafficking Hypothesis, which suggests that the downregulation of γ-Aminobutyric acid type A (GABAA) receptors, and upregulation of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors play major roles in the establishment of SE is the most widely accepted hypothesis underlying BZD resistance. NMDA and AMPA are ionotropic glutamate receptor families that have important excitatory roles in the central nervous system (CNS). They are both essential in maintaining the normal function of the brain and are involved in a variety of neuropsychiatric diseases, including epilepsy. Based on animal and human studies, antagonists of NMDA and AMPA receptors have a significant impact in ending SE; albeit most of them are not yet approved to be in clinically therapeutic guidelines, due to their psychomimetic adverse effects. Although there is still a dearth of randomized, prospective research, NMDA antagonists such as ketamine, magnesium sulfate, and the AMPA antagonist, perampanel, are regarded to be reasonable optional adjuvant therapies in controlling SE, refractory SE (RSE) or super-refractory SE (SRSE), though there are still a lack of randomized, prospective studies. This review seeks to summarize and update knowledge on the SE development hypothesis, as well as clinical trials using NMDA and AMPA antagonists in animal and human studies of SE investigations.

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“…In a lithium–pilocarpine mice model, memantine prevented cognitive impairments post-status epilepticus [ 122 ]. In a pentylenetetrazole (PTZ) model of seizures, memantine prevented convulsions and the development of morphological changes [ 123 ].…”

Section: Nmdar Modulators Currently In Usementioning

confidence: 99%

Targeting NMDA Receptor Complex in Management of Epilepsy

2022

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N-methyl-D-aspartate receptors (NMDARs) are widely distributed in the central nervous system (CNS) and play critical roles in neuronal excitability in the CNS. Both clinical and preclinical studies have revealed that the abnormal expression or function of these receptors can underlie the pathophysiology of seizure disorders and epilepsy. Accordingly, NMDAR modulators have been shown to exert anticonvulsive effects in various preclinical models of seizures, as well as in patients with epilepsy. In this review, we provide an update on the pathologic role of NMDARs in epilepsy and an overview of the NMDAR antagonists that have been evaluated as anticonvulsive agents in clinical studies, as well as in preclinical seizure models.

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Memantine attenuates cognitive impairments after status epilepticus induced in a lithium–pilocarpine model

Cited by 8 publications

References 14 publications

Validating a model of benzodiazepine refractory nerve agent-induced status epilepticus by evaluating the anticonvulsant and neuroprotective effects of scopolamine, memantine, and phenobarbital

Validating a model of benzodiazepine refractory nerve agent-induced status epilepticus by evaluating the anticonvulsant and neuroprotective effects of scopolamine, memantine, and phenobarbital

The Roles of Glutamate Receptors and Their Antagonists in Status Epilepticus, Refractory Status Epilepticus, and Super-Refractory Status Epilepticus

Targeting NMDA Receptor Complex in Management of Epilepsy

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