Abstract
ABSTRACTFocal neocortical epilepsy is a common form of epilepsy and there is a need to develop animal models that allow the evaluation of novel therapeutic strategies to treat this type of epilepsy. Tetanus toxin (TeNT) injection into the rat visual cortex induces focal neocortical epilepsy without preceding status epilepticus. The latency to first seizure ranged from 3 to 7 days. Seizure duration was bimodal, with both short (approximately 30 s) and long-lasting (>100 s) seizures occurring in the same animals. Seizures were accompanied by non-motor features such as behavioural arrest, or motor seizures with or without evolution to generalized tonic-clonic seizures. Seizures were more common during the sleep phase of a light-dark cycle. Seizure occurrence was not random, and tended to cluster with significantly higher probability of recurrence within 24 h of a previous seizure. Across animals, the number of seizures in the first week could be used to predict the number of seizures in the following 3 weeks. The TeNT model of occipital cortical epilepsy is a model of acquired focal neocortical epilepsy that is well-suited for preclinical evaluation of novel anti-epileptic strategies. We provide here a detailed analysis of the epilepsy phenotypes, seizure activity, electrographic features and the semiology. In addition, we provide a predictive framework that can be used to reduce variation and consequently animal use in preclinical studies of potential treatments.
Highlights
Animal models of epilepsies are an invaluable tool to test novel anti-epileptic treatments
An approach to refine the model by predicting the number of seizures from early data There was a significant and notable correlation between the number of seizures in the first week and the number that occurred during the remaining recording period. We assessed this correlation for its predictive ability using a Gaussian process model with a linear kernel (Fig. 6A-C). This model of the data indicates, for example, that, if the number of seizures during the first week of seizures is between 12 and 17 for a given animal, that animal may be predicted to have between 20 and DISCUSSION In this study, we demonstrate that application of Tetanus toxin (TeNT) into the rat visual cortex produces a model of occipital cortical epilepsy
The high rate of induction of epilepsy associated with very low morbidity and mortality indicates that this is a well-tolerated and reproducible rat model of epilepsy, and may be considered a refinement of other models (Wykes et al, 2012)
Summary
Animal models of epilepsies are an invaluable tool to test novel anti-epileptic treatments. The most commonly used rodent models of epilepsy rely on chemoconvulsants such as kainic acid or pilocarpine, or on electrical stimulation, to induce status epilepticus (SE), which is followed by spontaneous recurrent seizures. Received 20 June 2018; Accepted 12 November 2018 phosphatase and tensin homolog (Pten) or related signalling molecules to generate malformations of cortical development (Wong and Roper, 2016). All these models are useful, there is a need for a model of adult-onset neocortical epilepsy with a well-defined focus. This study characterises an animal model of adult-onset focal neocortical epilepsy that can support studies of potential treatments
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