The Search for New Screening Models of Pharmacoresistant Epilepsy: Is Induction of Acute Seizures in Epileptic Rodents a Suitable Approach?

The Search for New Screening Models of Pharmacoresistant Epilepsy: Is Induction of Acute Seizures in Epileptic Rodents a Suitable Approach? Neurochem Res. 2016 Aug 8; Authors: Löscher W Abstract Epilepsy, a prevalent neurological disease characterized by spontaneous recurrent seizures (SRS), is often refractory to treatment with anti-seizure drugs (ASDs), so that more effective ASDs are urgently needed. For this purpose, it would be important to develop, validate, and implement new animal models of pharmacoresistant epilepsy into drug discovery. Several chronic animal models with difficult-to-treat SRS do exist; however, most of these models are not suited for drug screening, because drug testing on SRS necessitates laborious video-EEG seizure monitoring. More recently, it was proposed that, instead of monitoring SRS, chemical or electrical induction of acute seizures in epileptic rodents may be used as a surrogate for testing the efficacy of novel ASDs against refractory SRS. Indeed, several ASDs were shown to lose their efficacy on acute seizures, when such seizures were induced by pentylenetetrazole (PTZ) in epileptic rather than nonepileptic rats, whereas this was not observed when using the maximal electroshock seizure test. Subsequent studies confirmed the loss of anti-seizure efficacy of valproate against PTZ-induced seizures in epileptic mice, but several other ASDs were more potent against PTZ in epileptic than nonepileptic...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research