Cerebrospinal fluid microRNAs are potential biomarkers of temporal lobe epilepsy and status epilepticus

Abstract

There is a need for diagnostic biomarkers of epilepsy and status epilepticus to support clinical examination, electroencephalography and neuroimaging. Extracellular microRNAs may be potentially ideal biomarkers since some are expressed uniquely within specific brain regions and cell types. Cerebrospinal fluid offers a source of microRNA biomarkers with the advantage of being in close contact with the target tissue and sites of pathology. Here we profiled microRNA levels in cerebrospinal fluid from patients with temporal lobe epilepsy or status epilepticus, and compared findings to matched controls. Differential expression of 20 microRNAs was detected between patient groups and controls. A validation phase included an expanded cohort and samples from patients with other neurological diseases. This identified lower levels of miR-19b in temporal lobe epilepsy compared to controls, status epilepticus and other neurological diseases. Levels of miR-451a were higher in status epilepticus compared to other groups whereas miR-21-5p differed in status epilepticus compared to temporal lobe epilepsy but not to other neurological diseases. Targets of these microRNAs include proteins regulating neuronal death, tissue remodelling, gliosis and inflammation. The present study indicates cerebrospinal fluid contains microRNAs that can support differential diagnosis of temporal lobe epilepsy and status epilepticus from other neurological and non-neurological diseases.

Discovery and validation of blood microRNAs as molecular biomarkers of epilepsy: Ways to close current knowledge gaps

“…Studies in models of intracerebral hemorrhage and stroke confirm that various brain‐enriched miRNAs enter the circulation within hours of the event . Cerebrospinal fluid contains neurologic disease‐specific differences in levels of various miRNAs . In addition, there is growing evidence of controlled release and paracrine signaling that is mediated via exosomes, which occur under both physiologic and pathophysiologic conditions .…”

MicroRNA‐induced silencing in epilepsy: Opportunities and challenges for clinical application

“…Another very recent study has identified differential expression of miR‐19b‐3p, miR‐21‐5p, and miR‐451a in CSF samples from patients with TLE or status epilepticus that might be useful to distinguish between these disorders (Raoof et al, ). Notably, this study also provided some insight into how microRNAs are transported in the CSF by assessing the relative amounts of miR‐19b‐3p, miR‐21‐5p, and miR‐451a bound to Argonaute2 or packed into exosomes in CSF.…”

“…Since their discovery, microRNAs have been suggested as potential biomarkers in many diseases, including neurological disorders such as Alzheimer's disease (Femminella et al, 2015;Dangla-Valls et al, 2016), Parkinson's disease (Hoss et al, 2016;Thome et al, 2016), Multiple Sclerosis (Jr Ode et al, 2013), and epilepsy (Wang et al, 2015a;Raoof et al, 2017). MicroRNAs are expressed in various body fluids including blood, cerebrospinal fluid (CSF), urine, ascetic fluid, amniotic fluid, and tears (Cortez et al, 2011), where they demonstrate remarkable stability.…”

Altered Biogenesis and MicroRNA Content of Hippocampal Exosomes Following Experimental Status Epilepticus

“…Altered expression of miRNAs has been reported within exosomes recovered from blood samples in patients with temporal lobe epilepsy (Yan et al, 2017) and dysregulation of miRNA editing has been reported in exosomes in non-CNS disease (Nigita et al, 2018). We recently found that cerebrospinal fluid from patients who experienced status epilepticus displayed different exosome miRNA content compared to other neurological diseases (Raoof et al, 2017). Functional studies suggest exosomes from human bone marrow-derived mesenchymal stem cells may regulate a neuro-inflammatory component in epilepsy (Long et al, 2017).…”