The World Health Organization estimates that globally 2.4 million people are diagnosed with
epilepsy each year. In nearly 30% of these cases,
epilepsy cannot be properly controlled by
antiepileptic drugs. More importantly, treatments to prevent or modify epileptogenesis do not exist. Therefore, novel
therapies are urgently needed. In this respect, it is important to identify which patients will develop
epilepsy and which individually tailored treatment is needed. However, currently, we have no tools to identify the patients at risk, and diagnosis of epileptogenesis remains as a major unmet medical need, which relates to lack of diagnostic
biomarkers for epileptogenesis. As the epileptogenic process in humans is typically slow, the use of animal models is justified to speed up
biomarker discovery. We aim to summarize recommendations for molecular
biomarker research and propose a standardized procedure for
biomarker discovery in rat models of epileptogenesis. The potential of many phylogenetically conserved circulating noncoding small RNAs, including
microRNAs (
miRNAs), as
biomarkers has been explored in various
brain diseases, including
epilepsy. Recent studies show the feasibility of detecting
miRNAs in blood in both experimental models and human
epilepsy. However, the analysis of circulating
miRNAs in rodent models is challenging, which relates both to the lack of standardized sampling protocols and to analysis of
miRNAs. We will discuss the issues critical for preclinical plasma
biomarker discovery, such as documentation, blood and brain tissue sampling and collection, plasma separation and storage,
RNA extraction, quality control, and
RNA detection. We propose a protocol for standardization of procedures for discovery of circulating
miRNA biomarkers in rat models of epileptogenesis. Ultimately, we hope that the preclinical standardization will facilitate clinical
biomarker discovery for epileptogenesis in man.