A model of 'epileptic tolerance' for investigating neuroprotection, epileptic susceptibility and gene...

Previous insult, for example, sustained epileptic seizures, confers a substantial temporary protection against the cellular damage induced by subsequent epileptic challenge. Here we describe a useful model of this so-called 'epileptic tolerance'. Expression of a status epilepticus was triggered by infusing the excitotoxic agent, kainate, into the right hippocampus of adult rats. An appropriate dose of kainate was used to cause brain damage in the homolateral, but not contralateral, hippocampus. At various times following this preconditioning insult, kainate was then re-administered into the lateral ventricle and neuroprotection was observed in the contralateral side between 1 and 15 days later. This model can be used to investigate the mechanisms of this endogenous neuroprotection. It is also particularly suitable for studying the epileptic susceptibility, as reflected by the modifications of the after-discharge threshold, as well as any changes in gene expression induced associated with the preconditioning episode.