Inhibition of microRNA-129-2-3p protects against refractory temporal lobe epilepsy by regulating GABRA1.

BACKGROUND: Accumulating evidence demonstrates that certain microRNAs play critical roles in epileptogenesis. Our previous studies found microRNA (miR)-129-2-3p was induced in patients with refractory temporal lobe epilepsy (TLE). In this study, we aimed to explore the role of miR-129-2-3p in TLE pathogenesis. METHOD: By bioinformatics, we predicted miR-129-2-3p may target the gene GABRA1 encoding the GABA type A receptor subunit alpha 1. Luciferase assay was used to investigate the regulation of miR-129-2-3p on GABRA1 3'UTR. The dynamic expression of miR-129-2-3p and GABRA1 mRNA and protein levels were measured in primary hippocampal neurons and a rat kainic acid (KA)-induced seizure model by quantitative reverse transcription-polymerase chain reaction (qPCR), Western blotting, and immunostaining. MiR-129-2-3p agomir and antagomir were utilized to explore their role in determining GABRA1 expression. The effects of targeting miR-129-2-3p and GABRA1 on epilepsy were assessed by electroencephalography (EEG) and immunostaining. RESULTS: Luciferase assay, qPCR, and Western blot results suggested GABRA1 as a direct target of miR-129-2-3p. MiR-129-2-3p level was significantly upregulated, whereas GABRA1 expression downregulated in KA-treated rat primary hippocampal neurons and KA-induced seizure model. In vivo knockdown of miR-129-2-3p by antagomir alleviated the seizure-like EEG findings in accordance with the upregulation of GABRA1. Furthermore, the seizure-suppressing effect of the antagomir was partly GABRA1 dependent. CONCLUSIONS: The results suggested GABRA1 as a target of miR-129-2-3p in rat primary hippocampal neurons and a rat kainic acid (KA) seizure model. Silencing of miR-129-2-3p exerted a seizure-suppressing effect in rats. MiR-129-2-3p/GABRA1 pathway may represent a potential target for the prevention and treatment of refractory epilepsy.

Delayed Anastomotic Occlusion after Direct Revascularization in Adult Hemorrhagic Moyamoya Disease.

Delayed anastomotic occlusion occurred in a considerable proportion of hemorrhagic moyamoya disease (MMD) patients undergoing direct revascularization. This study aimed to investigate the predictors and outcomes of delayed anastomotic occlusion in adult hemorrhagic MMD. The authors retrospectively reviewed 87 adult hemorrhagic MMD patients. Univariate and multivariate logistic regression analyses were performed. After an average of 9.1 ± 6.9 months of angiographic follow-up, the long-term graft patency rates were 79.8%. The occluded group had significantly worse angiogenesis than the non-occluded group (p < 0.001). However, the improvement of dilated anterior choroidal artery-posterior communicating artery was similar (p = 0.090). After an average of 4.0 ± 2.5 years of clinical follow-up, the neurological statues and postoperative annualized rupture risk were similar between the occluded and non-occluded groups (p = 0.750; p = 0.679; respectively). In the multivariate logistic regression analysis, collateral circulation Grade III (OR, 4.772; 95% CI, 1.184-19.230; p = 0.028) and preoperative computed tomography perfusion (CTP) Grade I-II (OR, 4.129; 95% CI, 1.294-13.175; p = 0.017) were independent predictors of delayed anastomotic occlusion. Delayed anastomotic occlusion in adult hemorrhagic MMD might be a benign phenomenon. Good collateral circulation (Grade III) and compensable preoperative intracranial perfusion (CTP Grade I-II) are independent predictors for this phenomenon. Moreover, the delayed anastomotic occlusion has no significant correlations with the long-term angiographic and neurological outcomes, except neoangiogenesis.