Integrated bioinformatics and validation to construct lncRNA-miRNA-mRNA ceRNA network in status epilepticus.

Background: Status epilepticus (SE) is a neurologic emergency with characteristic of prolonged seizure activity. However, the investigation of lncRNA based competing endogenous RNAs (ceRNAs) network in SE still requires further elucidation. This study aims to construct the ceRNA network and uncover the related mechanism in SE. Methods: The C57BL/6 mice pilocarpine-induced (SE) model was established (i.p. injection, 300 mg/kg) (n = 3). RNA-Sequencing was carried out and identified the differential expressed genes (DEGs). GO annotations, KEGG, and GSEA analysis were performed to study the underlying mechanism and pathways of the DEGs. Further, the protein-protein interaction (PPI) network and ceRNA network were visualized by Cytoscape software. The expression level of differential expressed genes involved in the ceRNA network was detected by qRT-PCR. Results: A total of 345 DE-mRNAs, 84 DE-lncRNAs, and 5 DE-miRNAs were screened out. Subsequently, the functional analysis suggested that angiogenesis, inflammation, and neuron related biological processes were enriched in SE. The constructed ceRNA network-1 contained 7 up-regulated DE-mRNAs (Arid5a, Adm, Insig1, Midn, Btaf1, Per1, Slc25a25), 1 down-regulated DE-miRNA (mmu-miR-6413), and 1 up-regulated DE-lncRNA (Zmiz1os1). The ceRNA network-2 contained 2 down-regulated DE-mRNAs (Rab27a and Lrp2), 1 up-regulated DE-miRNAs (mmu-miR-139-5p), and 1 down-regulated DE-lncRNA (Gm15883). Conclusion: For the first time this study present the expression profile and potential function of lncRNAs in C57BL/6 mice with SE. These results provided novel insights into the discovery of genetic biomarkers for SE.

The Impact of Volume Factor on the Long-Term Outcome of Gamma Knife Radiosurgery for Sporadic Cerebral Cavernous Malformations.

OBJECTIVE: We aimed to evaluate the long-term outcome of gamma knife radiosurgery (GKRS) for the treatment of sporadic cerebral cavernous malformation (CCM), especially the influence of lesion volume on annual hemorrhage rate (AHR) of patients with CCM after GKRS. METHODS: Fifty-one single-lesion patients with a history of hemorrhage who underwent radiosurgery at our institution were included and divided into 2 groups (A and B), based on their lesion volume. Group A included 25 patients with lesion volumes >1 cm3, whereas group B included 26 patients with lesion volumes ≤1 cm3. The clinical data of the patients were retrospectively analyzed. RESULTS: All patients were followed up for more than 4 years after GKRS. The calculated AHR before GKRS was 18.49% in group A and 10.16% in group B. The calculated AHR after GKRS was 5.43% and 0.99% for groups A and B, respectively. Significant differences in AHR after GKRS were identified between group A and group B (P = 0.011). Thirty-seven patients with sporadic CCM (14 in group A, 23 in group B) experienced symptom improvement, and significant differences in symptom improvement were observed between group A and group B (P = 0.009). CONCLUSIONS: GKRS decreased the risk of hemorrhage and was beneficial for symptomatic improvement in patients with sporadic CCM with a history of hemorrhage. The long-term clinical outcomes for patients with sporadic CCM with small lesion volumes (≤1 cm3) were better than those of patients with sporadic CCM with large lesion volumes (>1 cm3).

LncRNA TUG1 inhibits neuronal apoptosis in status epilepticus rats via targeting the miR-421/mTOR axis.

Status epilepticus (SE) induces apoptosis of hippocampal neurons. However, the underlying mechanism in SE is not fully understood. Recently, lncRNA TUG1 is reported as a significant mediator in neuronal development. In present study, we aimed to investigate whether lncRNA TUG1 induces apoptosis of hippocampal neurons in SE rat models. TUG1 expression in serum of normal volunteers and SE patients, SE rats and neurons with epileptiform discharge was detected. SE rat model was established and intervened with TUG1 to evaluate hippocampal neuronal apoptosis. The experiments in vitro were further performed in neurons with epileptiform discharge to verify the effects of TUG1 on neuronal apoptosis of SE rats. The downstream mechanism of TUG1 was predicted and verified. miR-421 was intervened to perform the rescue experiments. Levels of oxidative stress and inflammation-related factors and mTOR pathway-related proteins in SE rats and hippocampal neurons were detected. TUG1 was highly expressed in serum of SE patients, SE rats and neurons with epileptiform discharge. Inhibition of TUG1 relieved pathological injury, oxidative stress and inflammation and reduced neuronal apoptosis in SE rats, which were further verified in hippocampal neurons. TUG1 upregulated TIMP2 expression by targeting miR-421. Overexpressed miR-421 inhibited hippocampal neuronal apoptosis. TUG1 knockout inactivated the mTOR pathway via the miR-421/TIMP2 axis to relieve neuronal apoptosis, oxidative stress and inflammation in SE rats and hippocampal neurons. Taken together, these findings showed that downregulation of lncRNA TUG1 inhibited apoptosis of hippocampal neurons in SE rats, and attenuated oxidative stress and inflammation damage through regulating the miR-421/mTOR axis.