Anti-inflammatory effects of levetiracetam in experimental autoimmune encephalomyelitis

Thöne, Jan; Ellrichmann, Gisa; Faustmann, Pedro M.; Gold, Ralf; Haghikia, Aiden

doi:10.1016/j.intimp.2012.05.021

Cited by 10 publications

(5 citation statements)

References 16 publications

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“…These investigations ascribe the therapeutic effects of antiepileptic drugs to their inhibitory action of histone deacetylase. Furthermore, TPM and LEV provide additional benefits such as neuroprotection and anti-inflammation, which are involved in the pathogenesis of AD ( Belcastro et al, 2011 ; Thöne et al, 2012 ). However, it remains uncertain whether these antiepileptic drugs can reverse neuropathology and cognitive deficits via maintaining or restoring the activities of neuronal networks in AD transgenic mice.…”

Section: Introductionmentioning

confidence: 99%

Levetiracetam alleviates cognitive decline in Alzheimer’s disease animal model by ameliorating the dysfunction of the neuronal network

Zheng

Zhang

et al. 2022

Front. Aging Neurosci.

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BackgroundPatients with Alzheimer’s disease (AD) have a significantly higher risk of seizures than other individuals in an age-matched population, suggesting a close association between epilepsy and AD. We aimed to examine the effects of levetiracetam (LEV)—a drug for treating seizures—on learning and memory and the neuropathological features of AD.MethodsWe crossbred APP23 mice with microtubule-associated protein tau (MAPT) transgenic mice to generate APP23/MAPT mice. These mice were treated with different concentrations of LEV in the presence of kainic acid (KA) for 3 months.ResultsLow doses of LEV alleviated the effects of KA on memory defects in APP23/MAPT mice. Mechanistic investigations showed that low concentrations of LEV decreased tau phosphorylation by reducing the activities of cyclin-dependent kinase 5 and glycogen synthase kinase 3α/β, thus rescuing neurons from synaptic dystrophy and apoptosis. Low doses of LEV inhibited the effects of KA (i.e., inducing neuroinflammation and impairing the autophagy of amyloid β-peptide), thus improving cognitive decline. High concentrations of LEV decreased the production and deposition of amyloid β-peptide (Aβ) by reducing the expression of β-site APP-cleaving enzyme 1 and presenilin 1. However, high concentrations of LEV also induced neuronal apoptosis, decreased movement ability in mice, and did not alleviate cognitive decline in AD mice.ConclusionOur results support the hypothesis that aberrant network activity contributes to the synaptic and cognitive deficits in APP23/MAPT mice. A low concentration of LEV may help ameliorate abnormalities of AD; however, a high LEV concentration did not induce similar results.

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Section: Introductionmentioning

confidence: 99%

Levetiracetam alleviates cognitive decline in Alzheimer’s disease animal model by ameliorating the dysfunction of the neuronal network

Zheng

Zhang

et al. 2022

Front. Aging Neurosci.

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“…The activity of topiramate (TPM) and levetiracetam (LEV) as HDAC inhibitor has been demonstrated . Additionally, TPM and LEV could exert positive effects on neuroprotection and anti‐inflammation, both of which are involved in AD pathogenesis . Hence, it is significant and of interest to investigate the effects of antiepileptic drugs (TPM and LEV) on the behavioral performance and neuropathology in an AD mouse model.…”

Section: Introductionmentioning

confidence: 99%

Antiepileptics Topiramate and Levetiracetam Alleviate Behavioral Deficits and Reduce Neuropathology in APPswe/PS1dE9 Transgenic Mice

Shi

Wang²,

Tian

et al. 2013

CNS Neurosci Ther

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“…It is currently unknown whether the potency of levetiracetam in this model is related to the primary mechanism of action for levetiracetam (eg, SV2A modulation) or other potential mechanisms that reduce inflammation. 43,44 TMEV-mediated infection has been associated with innate immune system-mediated inflammation which includes a "cytokine storm". 10,13 Therefore, compounds with anti-inflammatory activity may be effective in this model.…”

Section: Discussionmentioning

confidence: 99%

Screening of prototype antiseizure and anti‐inflammatory compounds in the Theiler's murine encephalomyelitis virus model of epilepsy

et al. 2021

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Objective: Infection with Theiler's murine encephalomyelitis virus (TMEV) in C57Bl/6J mice results in handling-induced seizures and is useful for evaluating compounds effective against infection-induced seizures. However, to date only a few compounds have been evaluated in this model, and a comprehensive study of antiseizure medications (ASMs) has not yet been performed. Furthermore, as the TMEV infection produces marked neuroinflammation, an evaluation of prototype anti-inflammatory compounds is needed as well.Methods: Male C57Bl/6J mice were inoculated with TMEV (day 0) followed by daily administrations of test compounds (day 3-7) and subsequent handling sessions (day 3-7). Doses of ASMs, comprising several mechanistic classes, were selected based on previously published data demonstrating the effect of these compounds in reducing seizures in the 6 Hz model of pharmacoresistant seizures. Doses of anti-inflammatory compounds, comprising several mechanistic classes, were selected based on published evidence of reduction of inflammation or inflammation-related endpoints.Results: Several prototype ASMs reduced acute seizures following TMEV infection: lacosamide, phenytoin, ezogabine, phenobarbital, tiagabine, gabapentin, levetiracetam, topiramate, and sodium valproate. Of these, phenobarbital and sodium valproate had the greatest effect (>95% seizure burden reduction).Prototype anti-inflammatory drugs celecoxib, dexamethasone, and prednisone also moderately reduced seizure burden.

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Anti-inflammatory effects of levetiracetam in experimental autoimmune encephalomyelitis

Cited by 10 publications

References 16 publications

Levetiracetam alleviates cognitive decline in Alzheimer’s disease animal model by ameliorating the dysfunction of the neuronal network

Levetiracetam alleviates cognitive decline in Alzheimer’s disease animal model by ameliorating the dysfunction of the neuronal network

Antiepileptics Topiramate and Levetiracetam Alleviate Behavioral Deficits and Reduce Neuropathology in APPswe/PS1dE9 Transgenic Mice

Screening of prototype antiseizure and anti‐inflammatory compounds in the Theiler's murine encephalomyelitis virus model of epilepsy

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