Effects of chronic treatment with levetiracetam on hippocampal field responses after pilocarpine-induced status epilepticus in rats

Mǎrgineanu, D.; Matagne, Alain; Kamiński, Rafał M.; Klitgaard, Henrik

doi:10.1016/j.brainresbull.2008.07.006

Cited by 41 publications

(33 citation statements)

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“…To our knowledge, however, none of these measures has been shown to correlate with an effect of drug treatment on development of spontaneous seizures after SE. For instance, in the study by Margineanu et al (2008), administration of levetiracetam after a pilocarpine-induced SE was shown to prevent alterations in hippocampal field responses, but the same group (Klitgaard et al, 2001) reported that this treatment did not reduce the incidence of rats developing epilepsy, which was subsequently confirmed by our group in another SE model . Dudek et al (2008) criticized our study because we monitored the animals for only 1 week by video-EEG.…”

Section: Antiepileptogenesis After Brain Insultsmentioning

confidence: 49%

“…This negative outcome of levetiracetam studies in post-SE models was unexpected and gave rise to critical arguments on study design used for drug testing in the SE models (Dudek et al, 2008). It is noteworthy that Margineanu et al (2008) reported that, although prophylactic treatment with levetiracetam after a pilocarpine-induced SE did not seem to prevent development of spontaneous seizures, it completely prevented the development of hippocampal hyperexcitability (i.e., increased amplitude of population spike recorded in the dentate gyrus and reduced paired-pulse inhibition in the CA1 area). Furthermore, levetiracetam has been found to exert antiepileptogenic or disease-modifying effects in spontaneously epileptic rats (Yan et al, 2005;Russo et al, 2009), indicating that studies on kindling acquisition may be more predictive for such effects than data from SE models (see also discussion in section IV).…”

mentioning

confidence: 99%

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Prevention or Modification of Epileptogenesis after Brain Insults: Experimental Approaches and Translational Research

Löscher¹,

Brandt²

2010

Pharmacol Rev

361

366

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Section: Antiepileptogenesis After Brain Insultsmentioning

confidence: 49%

mentioning

confidence: 99%

Prevention or Modification of Epileptogenesis after Brain Insults: Experimental Approaches and Translational Research

Löscher¹,

Brandt²

2010

Pharmacol Rev

361

366

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“…4). Treated animals also had reduced paired-pulse inhibition in CA1 compared to untreated animals (Margineanu and others 2008) (Fig. 5).…”

Section: Poststatus Epilepticus Modelsmentioning

confidence: 87%

“…In contrast, another study that treated with valproate for 4 weeks after electrical-induced status epilepticus found that treatment did not prevent spontaneous seizures or affect seizure frequency or severity (Brandt and others 2006). A drug that has shown some promise poststatus is levetiracetam (Margineanu and others 2008). Animals treated with leviteracetam for 21 days poststatus followed by a 3-day washout showed dose-dependent reduction in the increased population spike amplitude in the dentate gyrus (Fig.…”

Section: Poststatus Epilepticus Modelsmentioning

confidence: 99%

Is Epilepsy a Preventable Disorder? New Evidence from Animal Models

Giblin

Blumenfeld

2010

Neuroscientist

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Epilepsy accounts for 0.5% of the global burden of disease, and primary prevention of epilepsy represents one of the three 2007 NINDS Epilepsy Research Benchmarks. In the past decade, efforts to understand and intervene in the process of epileptogenesis have yielded fruitful preventative strategies in animal models. This article reviews the current understanding of epileptogenesis, introduces the concept of a "critical period" for epileptogenesis, and examines strategies for epilepsy prevention in animal models of both acquired and genetic epilepsies. We discuss specific animal models, which may yield important insights into epilepsy prevention including kindling, poststatus epilepticus, prolonged febrile seizures, traumatic brain injury, hypoxia, the tuberous sclerosis mouse model, and the WAG/Rij rat model of primary generalized epilepsy. Hopefully, further investigation of antiepileptogenesis in animal models will soon enable human therapeutic trials to be initiated, leading to long-term epilepsy prevention and improved patient quality of life. Keywords epileptogenesis; prevention; activity dependent; animal models; acquired epilepsy; idiopathic generalized epilepsy Epilepsy is a disorder characterized by chronically recurring seizures without clear precipitants. The age-adjusted prevalence of epilepsy is in the range of 4 to 10 per 1000 people in most locations (Sander 2003; Forsgren and others 2005). The burden associated with epilepsy is great, both for the individual with epilepsy and for society at large. Epilepsy can negatively impact cognitive function, is a source of social stigma and legal marginalization, causes increased mortality, economically contributes 0.5% of the global burden of disease, and is associated with an increased risk of psychiatric disorder (de Boer and others 2008). As such, epilepsy prevention is one of the three 2007 NINDS Epilepsy Research Benchmarks (Kelley and others 2009).Work on epilepsy prevention can for the most part be parsed into prevention of epilepsy after a known inciting event (acquired epilepsy), and prevention of epilepsy in genetic © The Author(s) 2010Corresponding Author: Hal Blumenfeld, Yale University School of Medicine, Departments of Neurology, Neurobiology, and Neurosurgery, 333 Cedar Street, New Haven, CT 06520-8018, hal.blumenfeld@yale.edu. Declaration of Conflicting InterestsThe authors declared no potential conflicts of interests with respect to the authorship and/or publication of this article. NIH Public Access Author ManuscriptNeuroscientist. Author manuscript; available in PMC 2010 July 28. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript models where the time of epilepsy development is well characterized and may be dependent on a transient developmental milieu. Both of these approaches rest upon identification of epileptogenesis, understanding of the und erlying mechanisms of epilepsy development, and intervention targeted to these mechanisms in an appropriate time period. While prevention of epilepsy in human su...

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“…In addition, the development of hippocampal hyperexcitability, as manifested by increased population spike amplitude in the dentate gyrus and reduced paired-pulse inhibition in the CA1 area, was inhibited [62]. With the exception of one study [59], levetiracetam has also exhibited neuroprotective properties in SE studies [28,63] and an ability to suppress seizure-induced neurogenesis [62], whereas cognitive impairment induced by SE was not prevented [59,63].…”

Section: Levetiracetammentioning

confidence: 99%

The Potential of Antiseizure Drugs and Agents that Act on Novel Molecular Targets as Antiepileptogenic Treatments

2014

Self Cite

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A major goal of contemporary epilepsy research is the identification of therapies to prevent the development of recurrent seizures in individuals at risk, including those with brain injuries, infections, or neoplasms; status epilepticus; cortical dysplasias; or genetic epilepsy susceptibility. In this review we consider the evidence largely from preclinical models for the antiepileptogenic activity of a diverse range of potential therapies, including some marketed antiseizure drugs, as well as agents that act by immune and inflammatory mechanisms; reduction of oxidative stress; activation of the mammalian target of rapamycin or peroxisome proliferatoractivated receptors γ pathways; effects on factors related to thrombolysis, hematopoesis, and angiogenesis; inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reducatase; brainderived neurotrophic factor signaling; and blockade of α2 adrenergic and cannabinoid receptors. Antiepileptogenesis refers to a therapy of which the beneficial action is to reduce seizure frequency or severity outlasting the treatment period. To date, clinical trials have failed to demonstrate that antiseizure drugs have such disease-modifying activity. However, studies in animal models with levetiracetam and ethosuximide are encouraging, and clinical trials with these agents are warranted. Other promising strategies are inhibition of interleukin 1β signaling by drugs such as VX-765; modulation of sphingosine 1-phosphate signaling by drugs such as fingolimod; activation of the mammalian target of rapamycin by drugs such as rapamycin; the hormone erythropoietin; and, paradoxically, drugs such as the α2 adrenergic receptor antagonist atipamezole and the CB1 cannabinoid antagonist SR141716A (rimonabant) with proexcitatory activity. These approaches could lead to a new paradigm in epilepsy drug therapy where treatment for a limited period prevents the occurrence of spontaneous seizures, thus avoiding lifelong commitment to symptomatic treatment.

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Effects of chronic treatment with levetiracetam on hippocampal field responses after pilocarpine-induced status epilepticus in rats

Cited by 41 publications

References 23 publications

Prevention or Modification of Epileptogenesis after Brain Insults: Experimental Approaches and Translational Research

Prevention or Modification of Epileptogenesis after Brain Insults: Experimental Approaches and Translational Research

Is Epilepsy a Preventable Disorder? New Evidence from Animal Models

The Potential of Antiseizure Drugs and Agents that Act on Novel Molecular Targets as Antiepileptogenic Treatments

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