Effects of levetiracetam on hippocampal kindling in Noda epileptic rats

Ishimaru, Yuji; Serikawa, Tadao; Sasa, Masashi; Inaba, Hiroko; Tamura, Yoshiyuki; Ishimoto, Takahiro; Takasaki, Hideki; Sakamoto, Kazutaka; Yamaguchi, Kazuhide

doi:10.1016/j.brainres.2009.10.056

Cited by 8 publications

(3 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ishimaru et al . reported the antiepileptic effects of LEV on hippocampal kindling in NERs [ 49 ], and Inoue et al . also showed inhibition effects of traditional AEDs, phenobarbital (PB) and valproate (VPA), against seizures evoked by strong environmental stimuli in mature NERs [ 45 ].…”

Section: Generalized Tonic-clonic Seizure Models: Ier Ner and Wermentioning

confidence: 99%

Advances on genetic rat models of epilepsy

et al. 2015

Self Cite

View full text Add to dashboard Cite

Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: ‘phenotype to gene’ and ‘gene to phenotype’. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies.

show abstract

Section: Generalized Tonic-clonic Seizure Models: Ier Ner and Wermentioning

confidence: 99%

Advances on genetic rat models of epilepsy

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…Several other studies have also shown beneficial effects of LEV treatment in acute seizure models. For example, the development of kindling (a progressive increase in seizure severity induced by repeated brain stimulation at certain intervals), and kindling-related abnormal gene expression can be considerably modulated through daily application of LEV (15, 21, 22). …”

Section: Usefulness Of Lev For Easing Epileptogenesismentioning

confidence: 99%

“…Several studies report promising outcomes such as delayed development of hippocampal hyperexcitability, restraint of electrographic seizures, diminishment in the abnormal migration of newly born neurons into the dentate hilus, and inhibition of inflammatory responses in SE models (20, 26, 27, 29). There are also reports of mitigation of synaptic potentiation and abnormal expression of IEGs, and prevention of abnormal accumulation of 7S SNARE complexes and SV2 in kindling models (15, 22–24). However, some studies report no beneficial effects of LEV treatment after SE in terms of easing epileptogenesis or cognitive dysfunction (31, 32).…”

Section: Overall Conclusionmentioning

confidence: 99%

Prospects of Levetiracetam as a Neuroprotective Drug Against Status Epilepticus, Traumatic Brain Injury, and Stroke

Shetty

2013

Front. Neurol.

View full text Add to dashboard Cite

Levetiracetam (LEV) is an anti-epileptic drug commonly used for the treatment of partial onset and generalized seizures. In addition to its neuromodulatory and neuroinhibitory effects via its binding to the synaptic vesicle protein SV2A, multiple studies have suggested neuroprotective properties for LEV in both epileptic and non-epileptic conditions. The purpose of this review is to discuss the extent of LEV-mediated protection seen in different neurological conditions, the potential of LEV for easing epileptogenesis, and the possible mechanisms that underlie the protective properties of LEV. LEV has been found to be particularly beneficial for restraining seizures in animal models of spontaneous epilepsy, acute seizures, and status epilepticus (SE). However, its ability for easing epileptogenesis and cognitive dysfunction following SE remains controversial with some studies implying favorable outcomes and others reporting no beneficial effects. Efficacy of LEV as a neuroprotective drug against traumatic brain injury (TBI) has received much attention. While animal studies in TBI models have showed significant neuroprotection and improvements in motor and memory performance with LEV treatment, clinical studies suggest that LEV has similar efficacy as phenytoin in terms of its ability to prevent post-traumatic epilepsy. LEV treatment for TBI is also reported to have fewer adverse effects and monitoring considerations but electroencephalographic recordings suggest the presence of increased seizure tendency. Studies on stroke imply that LEV is a useful alternative to carbamazepine for preventing post-stroke seizures in terms of efficacy and safety. Thus, LEV treatment has promise for restraining SE-, TBI-, or stroke-induced chronic epilepsy. Nevertheless, additional studies are needed to ascertain the most apt dose, timing of intervention, and duration of treatment after the initial precipitating injury and the mechanisms underlying LEV-mediated beneficial effects.

show abstract