MiR-134 blockade prevents status epilepticus like-activity and is neuroprotective in cultured hippocampal neurons.

Status epilepticus (SE) is a life-threatening neurological disorder associated with significant morbidity and mortality. MicroRNAs (miRNAs) are small, non-coding RNAs that act post-transcriptionally modulating messenger RNA (mRNA) translation or stability which may have important roles in the pathogenesis of epilepsy. It has been reported that silencing microRNA-134 in vivo has significant neuroprotective and prolonged seizure-suppressive effects. However, the mechanism by which miR-134 inhibition suppressed seizures and whether miR-134 inhibition works in an in vitro model of SE, is unknown. Compared to a complex in vivo system, in vitro models of SE-like electrographic activity can be powerful tools to study this miRNA. Using a cell culture model of low Mg(2+) treatment of rat hippocampal neurons, we found SE-like electrographic activity increased expression of miR-134. Inhibiting expression of miR-134 using an inhibitor lentivirus with two miR-134 binding sites reduced SE-like electrographic activity in the hippocampal neurons and reduced neuronal death. This study provides direct evidence that inhibition of miR-134 can block status epilepticus-like discharges and is neuroprotective in hippocampal neuronal cultures and implies that inhibiting miR-134 may be a potential candidate for the clinical treatment of SE.

The anticonvulsant and neuroprotective effects of baicalin on pilocarpine-induced epileptic model in rats.

Baicalin, a flavonoid compound purified from plant Scutellaria baicalensis Georgi, has been reported to possess a wide variety of pharmacological properties including anti-oxidative, anti-apoptotic and neuroprotective properties. Oxidative stress can dramatically alter neuronal function and has been linked to status epilepticus (SE). However, the neuroprotective effect of baicalin on epilepsy is unclear. In this study we investigated whether Baicalin could exert anticonvulsant and neuroprotective effects in the pilocarpine-induced epileptic model in rats. To this end, we recorded the latency to first limbic seizure and SE and observed the incidence of SE and mortality. The changes of oxidative stress were measured 24 h after pilocarpine-induced SE. Nissl staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and Fluoro-Jade B staining were performed to detect the neuronal loss, apoptosis and degeneration in hippocampus 72 h after pilocarpine-induced seizure. Pretreatment with baicalin significantly delayed the onset of the first limbic seizures and SE, reduced the mortality rate, and attenuated the changes in the levels of lipid peroxidation, nitrite content and reduced glutathione in the hippocampus of pilocarpine-treated rats. Furthermore, we also found that baicalin attenuated the neuronal cell loss, apoptosis, and degeneration caused by pilocarpine-induced seizures in rat hippocampus. Collectively, these results indicated remarkable anticonvulsant and neuroprotective effects of baicalin and should encourage further studies to investigate baicalin as an adjuvant in epilepsy both to prevent seizures and to protect against seizure induced brain injury.