Background: Perampanel is a highly selective and non-competitive α-amino-3-hydroxy- 5 -methyl-4-isoxazole propionate (AMPA) receptor (AMPAR) antagonist, which has been licensed as an orally administered antiepileptic drug in more than 55 countries. Recently, perampanel was found to exert neuroprotective effects in hemorrhagic and ischemic stroke models.
Objective: In this study, the protective effect of perampanel was investigated.
Methods: The protective effect of perampanel was investigated in an in vitro Traumatic Neuronal Injury (TNI) model in primary cultured cortical neurons.
Results: We found that perampanel significantly preserved morphological changes, attenuated lactate dehydrogenase (LDH) release and inhibited caspase-3 activation after TNI. The TNI-induced necroptosis, as evidenced by flow cytometry, was markedly reduced by perampanel treatment. The results of western blot showed that perampanel decreased the expression and phosphorylation of the necroptotic factors, receptor protein interacting kinase 1 (RIPK1) and RIPK3. In addition, treatment with perampanel increased the phosphorylation of Akt and GSK3β in a time-dependent manner up to 24 h after TNI. Treatment with the Akt inhibitor LY294002 partially reversed the protective effects of perampanel.
Conclusion: Our present data suggest that necroptosis plays a key role in the pathogenesis of neuronal death after TNI, and that perampanel might have therapeutic potential for patients with Traumatic Brain Injury (TBI).
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/1871527319666201001110937 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Investigating the Relationship Between Anti-seizure Medications and Bleeding Disorders: A Comprehensive Review of the Current Literature.
Drugs Real World Outcomes
January 2025
Kabul University of Medical Sciences, Kabul, Afghanistan.
Anti-seizure medications (ASMs) are specific types of anticonvulsants used to treat epileptic seizures. However, several studies have shown an association between ASMs and an increased risk of hematological disorders, such as thrombocytopenia, aplastic anemia, and platelet function disorders leading to prolonged bleeding times. This review explores the existing literature on this topic, investigating a wide variety of ASMs, ranging from first-generation medications to newer ones.
View Article and Find Full Text PDFBDNF/Cyclin D1 Signaling System and Cognitive Performance After Perampanel and Lacosamide Treatment Singly or in Combination in an Experimental Model of Temporal Lobe Epilepsy.
Curr Issues Mol Biol
December 2024
Department of Anatomy, Histology and Embryology, Medical Faculty, Medical University Plovdiv, 4002 Plovdiv, Bulgaria.
Epilepsy is a common brain function disorder. The present study aims to evaluate the long-term effect of perampanel (PRM) and lacosamide (LCM), administered singly in a high-dose or in a low-dose combination of both, on comorbid anxiety, cognitive impairment, BDNF, and Cyclin D1 hippocampal expression in an experimental model of temporal lobe epilepsy with lithium-pilocarpine. PRM (3 mg/kg, p.
View Article and Find Full Text PDFThe Use of Perampanel in the Treatment of Lance-Adams Syndrome.
J Epilepsy Res
December 2024
Department of Neurology, Comprehensive Epilepsy Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lance Adams syndrome (LAS) is characterized by chronic action or intention myoclonus resulting from cerebral hypoxia. Perampanel, a non-competitive antagonist of aamino-3-hydroxy-5methyl-4 isooxazoleproprionic acid glutamate receptor, has demonstrated some efficacy in myoclonic epilepsy and other types of myoclonus. We report significant benefit in a patient with LAS treated with add on perampanel and provide a review of the relevant literature.
View Article and Find Full Text PDFImpact of Perampanel for First-Episode Seizures versus Usual Care on Clinical Outcome and Safety Profile Aspects of the Thai Experience.
J Epilepsy Res
December 2024
Neurological Surgery Unit, Department of Surgery, Phramongkutklao Hospital, Bangkok, Thailand.
Background And Purpose: Epilepsy increases poor outcomes in patients with post-traumatic brain injury and brain tumor-related epilepsy, for whom early seizure control is essential. Perampanel (PER) was a known third-generation antiepileptic drug for treatment all types of seizures. The objective of the study is to compare clinical outcomes and safety of PER administration as monotherapy.
View Article and Find Full Text PDFA multi-center, open-label, randomized clinical trial evaluating the preventive effect of perampanel on craniotomy-induced epileptogenesis in seizure-naive patients with supratentorial brain tumors: study protocol for a GRAMPAS trial.
Trials
December 2024
Department of Neurosurgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, Japan.
Background: Early seizures after craniotomy are significant perioperative complications that can adversely impact patient outcomes. Despite current guidelines advising against the routine use of antiseizure drugs for seizure after craniotomy prevention due to limited efficacy data, many clinicians continue prescribing them. This discrepancy highlights the need for robust evidence to guide clinical practice.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!