A novel animal model of acquired human temporal lobe epilepsy based on the simultaneous administration of kainic acid and lorazepam

Kienzler-Norwood, Friederike; Costard, Lara S.; Sadangi, Chinmaya; Müller, Philipp; Neubert, Valentin; Bauer, Sebastian; Rosenow, Felix; Norwood, Braxton A.

doi:10.1111/epi.13579

Cited by 22 publications

(26 citation statements)

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“…The KaL model also recapitulates essential characteristics of human TLE, such as hippocampal sclerosis and hippocampal‐onset epilepsy after a discreet seizure‐free period (Kienzler‐Norwood et al, ). Animals received 15 mg/kg kainic acid monohydrate (10 mg/ml in phosphate‐buffered saline, K0250, Sigma‐Aldrich, Germany) and 0.75 mg/kg lorazepam (2 mg/ml, Pfizer, Germany) that was administered subcutaneously, while the control animals received 15 mg/kg kainic acid monohydrate and 3 mg/kg lorazepam.…”

Section: Methodsmentioning

confidence: 99%

“…The aim of this study was to discover reference genes for two rat models of epilepsy: 8‐hr perforant pathway stimulation (PPS) (Norwood et al, ) and systemic kainate‐lorazepam (KaL) during epileptogenesis and/or chronic epilepsy, and after acute, noninjurious seizures (30‐min PPS) (Norwood et al, ). The mRNA expression levels of 15 (Kienzler‐Norwood et al, ) potential reference genes were determined in hippocampi from treated and control animals. Four different validated and established methods to determine expression stability were used: geNorm (Vandesompele et al, ), NormFinder (Andersen, Jensen, & Ørntoft, ), BestKeeper (Pfaffl, Tichopad, Prgomet, & Neuvians, ), and Delta‐Ct (ΔCt) (Silver, Best, Jiang, & Thein, ).…”

Section: Introductionmentioning

confidence: 99%

“…The mRNA expression levels of 15 (Kienzler-Norwood et al, 2017) potential reference genes were determined in hippocampi from treated and control animals. Four different validated and established methods to determine expression stability were used: geNorm (Vandesompele et al, 2002), NormFinder (Andersen, Jensen, & Ørntoft, 2004), Best-Keeper (Pfaffl, Tichopad, Prgomet, & Neuvians, 2004), and Delta-Ct (DCt) (Silver, Best, Jiang, & Thein, 2006).…”

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confidence: 99%

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Validation of reference genes for quantitative gene expression analysis in experimental epilepsy

Sadangi

Rosenow

Norwood

2017

J of Neuroscience Research

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To grasp the molecular mechanisms and pathophysiology underlying epilepsy development (epileptogenesis) and epilepsy itself, it is important to understand the gene expression changes that occur during these phases. Quantitative real-time polymerase chain reaction (qPCR) is a technique that rapidly and accurately determines gene expression changes. It is crucial, however, that stable reference genes are selected for each experimental condition to ensure that accurate values are obtained for genes of interest. If reference genes are unstably expressed, this can lead to inaccurate data and erroneous conclusions. To date, epilepsy studies have used mostly single, nonvalidated reference genes. This is the first study to systematically evaluate reference genes in male Sprague-Dawley rat models of epilepsy. We assessed 15 potential reference genes in hippocampal tissue obtained from 2 different models during epileptogenesis, 1 model during chronic epilepsy, and a model of noninjurious seizures. Reference gene ranking varied between models and also differed between epileptogenesis and chronic epilepsy time points. There was also some variance between the four mathematical models used to rank reference genes. Notably, we found novel reference genes to be more stably expressed than those most often used in experimental epilepsy studies. The consequence of these findings is that reference genes suitable for one epilepsy model may not be appropriate for others and that reference genes can change over time. It is, therefore, critically important to validate potential reference genes before using them as normalizing factors in expression analysis in order to ensure accurate, valid results.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Validation of reference genes for quantitative gene expression analysis in experimental epilepsy

Sadangi

Rosenow

Norwood

2017

J of Neuroscience Research

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“…Many available animal models of Mesial Temporal lobe epilepsy (mTLE), and in particular systemic KA administration, are induced by acute treatments that often are associated with high mortality and experimental variability rates (Hellier et al, 1998; McLin and Steward, 2006; Kienzler-Norwood et al, 2017). Modeling mTLE using experimental animals comprises, in general, three well-defined stages: First, an initiating insult to the brain, such as febrile seizures, head trauma, stroke, or strong seizures leading to status epilepticus (SE).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, several of the above-mentioned models induce varying mortality rates and are accompanied by severe animal welfare issues (Curia et al, 2008; Lévesque and Avoli, 2013; Lidster et al, 2016). Therefore, preclinical epilepsy research would benefit from more detailed and standardized protocols, with lower mortality rates and improved animal welfare, which could increase intra- and inter-laboratory reproducibility (Lidster et al, 2016; Kienzler-Norwood et al, 2017). …”

Section: Introductionmentioning

confidence: 99%

A Standardized Protocol for Stereotaxic Intrahippocampal Administration of Kainic Acid Combined with Electroencephalographic Seizure Monitoring in Mice

et al. 2017

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Lack of scientific reproducibility is a growing concern and weak experimental practices may contribute to irreproducibility. Here, we describe an optimized and versatile protocol for stereotaxic intrahippocampal administration of Kainic Acid (KA) in mice with a C57Bl6 background. In this protocol, KA administration is combined with in vivo recording of neuronal activity with wired and wireless setups. Following our protocol, KA administration results in a robust dose-dependent induction of low-level epileptiform activity or Status Epilepticus (SE) and induces previously characterized hallmarks of seizure-associated pathology. The procedure consists of three main steps: Craniotomy, stereotaxic administration of KA, and placement of recording electrodes in intrahippocampal, and subdural locations. This protocol offers extended possibilities compared to the systemic administration of KA, as it allows the researcher to accurately regulate the local dose of KA and resulting seizure activity, and permits the use and study of convulsive and non-convulsive KA doses, resulting in higher reproducibility and lower inter-individual variability and mortality rates. Caution should be taken when translating this procedure to different strains of mice as inter-strain sensitivity to KA has been described before. The procedure can be performed in ~1 h by a trained researcher, while intrahippocampal administration of KA without placing recording electrodes can be done in 25 min, and can be easily adapted to the titrated intrahippocampal administration of other drugs.

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Envisioning the role of inwardly rectifying potassium (Kir) channel in epilepsy

Akyüz

Köklü

Uner

et al. 2021

J of Neuroscience Research

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Epilepsy is a neurological disease characterized by two spontaneous seizures occurring within 24 hr, or two spontaneous seizures within 10 years after an unprovoked seizure (Fisher et al., 2014). The disease occurs by an increased tendency to generate seizures attributed to abnormal brain activity, caused by the disruption of the dynamic excitatory and inhibitory neuronal balance in the central nervous system (CNS) (Navidhamidi et al., 2017). Aberrant connectivity between neuronal networks may result in pathologically synchronized discharges and subsequently recurrent seizures (Aronica & Muhlebner, 2017). Epilepsy not only poses a significant burden on the patients and their families, but is also associated with significant social, behavioral, and economic effects (Tatum et al., 2009).Epilepsy affects people of all ages and has emerged as a global health concern affecting more than 70 million patients worldwide.Despite the recent advances in pre-clinical and clinical research, the

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A novel animal model of acquired human temporal lobe epilepsy based on the simultaneous administration of kainic acid and lorazepam

Cited by 22 publications

References 46 publications

Validation of reference genes for quantitative gene expression analysis in experimental epilepsy

Validation of reference genes for quantitative gene expression analysis in experimental epilepsy

A Standardized Protocol for Stereotaxic Intrahippocampal Administration of Kainic Acid Combined with Electroencephalographic Seizure Monitoring in Mice

Envisioning the role of inwardly rectifying potassium (Kir) channel in epilepsy

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