Expressions of Tumor Necrosis Factor Alpha and MicroRNA-155 in Immature Rat Model of Status Epilepticus and Children with Mesial Temporal Lobe Epilepsy

Abstract

Recently, the role of inflammation has attracted great attention in the pathogenesis of mesial temporal lobe epilepsy (MTLE), and microRNAs start to emerge as promising new players in MTLE pathogenesis. In this study, we investigated the dynamic expression patterns of tumor necrosis factor alpha (TNF-α) and microRNA-155 (miR-155) in the hippocampi of an immature rat model of status epilepticus (SE) and children with MTLE. The expressions of TNF-α and miR-155 were significantly upregulated in the seizure-related acute and chronic stages of MTLE in the immature rat model and also in children with MTLE. Modulation of TNF-α expression, either by stimulation using myeloid-related protein (MRP8) or lipopolysaccharide or inhibition using lenalidomide on astrocytes, leads to similar dynamic changes in miR-155 expression. Our study is the first to focus on the dynamic expression pattern of miR-155 in the immature rat of SE lithium-pilocarpine model and children with MTLE and to detect their relationship at the astrocyte level. TNF-α and miR-155, having similar expression patterns in the three stages of MTLE development, and their relationship at the astrocyte level may suggest a direct interactive relationship during MTLE development. Therefore, modulation of the TNF-α/miR-155 axis may be a novel therapeutic target for the treatment of MTLE.

microRNA s (9, 138, 181A, 221, and 222) and mesial temporal lobe epilepsy in developing brains

“…Kan et al (2012) profiled the miRNAs changes in human TLE [17]. Our previous experiments supported the role of inflammation-related miRNAs (miR-146a, -155, -21, and -132) and brain-specific miRNAs (miR-124 and -134) in the pathogenesis of MTLE in immature rat models and children [20,29,30].…”

“…Intra-peritoneal pilocarpine administration Clinical information on children with MTLE and controls has been described previously [20].…”

MicroRNAs as biomarkers in molecular diagnosis of refractory epilepsy

“…Up-regulated miRNAs includes miR-21, miR-23a, miR-23b, miR-24, miR-27a, miR-27b, miR-34a, miR-126, miR-132, miR-140, miR146a, miR-152, miR-210 and miR-212 while downregulated miRNAs includes miR-33, miR-138, miR-139, miR-187, miR-190, miR-218a, miR-301a, miR-551b and miR-935. Among the up-regulated miRNAs only three were mentioned in three human experiments, which are miR-21, miR-132 and miR-146a [30][31][32]. Of note, miR-134 is also an important microRNA that is up-regulated during epilepsy, which is only profiled in one human experiment of Jimenez-Manteos et al [23].…”

Inflammation-related and Brain-enriched MicroRNAs Influence the Activation of Microglia Response to In vitro Oxygen-Glucose Deprivation

“…Recent researches showed that inflammationrelated miRNAs, including miRs (146a, 21, 181a, 221, and 222), have a close relationship with multiple CNS diseases, including mesial temporal lobe epilepsy (MTLE) [13][14][15] , and ischemic injuries [16,17] . Seventy percent of experimentally-detected miRNAs are found in mamm-alian brain tissues [18] ; among these, at least seven brain-enriched miRNAs including miRs (124, 134, 9, 132, and 138) have been described.…”

“…Our research group is vigorously working to understand the mechanisms of many CNS diseases including meningitis [25][26][27] , intractable epilepsy [13,15,28] , and ischemic injuries [22] . Recent studies have shown that brain inflammation is an important factor contributing to almost all CNS diseases and activation of microglia is considered to be neuroinflammation hallmark.…”