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Considerable evidence suggest that a variety of Long-non-coding RNAs (LncRNAs) are widely implicated in several neurodegenerative disorders. The present study aims to investigate the regulatory effect of LncRNA 17A in an in vitro model of Alzheimer’s disease (AD). AD cell model was established by treating the SH-SY5Y cells with amyloid β peptide 1-42, and then the cells were transfected with 17A shRNA and pcDNA-17A. Apoptosis, migration, invasion and ELISA assays were performed to investigate the effect of differentiated 17A expression level on AD cell line. It was determined that 17A-overexpressing promotes autophagy, induces neurodegenration and deactivates GABAB signaling. In conclusion, our results demonstrated that the dysregulation of LncRNA 17A was involved in cellular functions and biological processes of neuroblastoma cells in an AD cell model, shedding light on the diagnostic value and therapeutic potential of LncRNA 17A for AD intervention.

Growth/differentiation factor-5 (GDF-5), a member of the transforming growth factor-beta (TGF-β) superfamily, has been shown to protect rat dopaminergic neurons against insult both in embryonic neuronal culture and in Parkinson’s disease models. However, whether GDF-5 exerts neuroprotective effects in hippocampal neurons is unclear. Here, we show that both mRNA levels and protein levels of GDF-5 are decreased in the mouse hippocampus upon kainic acid (KA) treatment. KA induced dramatic neuronal loss specifically in the cornu ammonis 1 (CA1) and CA3 areas of the mouse hippocampus, while intracerebral infusion of GDF-5 prevented this neuronal loss. The neuroprotective effects of GDF-5 were recapitulated by constitutively active bone morphogenetic protein type IB receptor (BMPRIB-CA) and could be blocked by BMPRI kinase inhibitor LDN-193189. Furthermore, the neuroprotective effects of GDF-5 were mediated through the prevention of apoptosis, which was indicated by terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining and reduced cleaved caspase 3 expression level. Thus, we conclude that GDF-5 protects hippocampal neurons against KA-induced neurodegeneration by signaling through BMPRIB, suggesting a therapeutic potential for GDF-5 in neurodegenerative diseases.

Background miR-15b is significantly and consistently downregulated in different clinical phenotypes of myasthenia gravis (MG). However, its role in pathogenesis of MG is still not clear. This study aimed to explore the function of miR-15b in MG. Material and methods Blood samples from early-onset MG, late-onset MG, thymoma patients, and healthy participants were collected. The expression pattern of IL-15 and miR-15b was identified by qRT-PCR and ELISA in patient serum and mouse tissue samples. The regulative role of miR-15b on IL-15 expression was verified in an experimental autoimmune myasthenia gravis (EAMG) mice model. Results qRT-PCR and ELISA showed that miR-15b expression was significantly lower and IL-15 expression was significantly higher in all EMG, LMG, and thymoma cases compared to healthy controls. Based on mouse model, we confirmed that miR-15b knockdown could increase IL-15 expression in healthy mice, while miR-15b overexpression could inhibit IL-15 expression in EAMG mice. Through searching in bioinformatics databases, we identified a highly conserved consequential pairing between IL-15 and miR-15b. Subsequent dual luciferase assay further verified this match. Conclusions This study is the first to report the miR-15b-IL-15 axis can directly regulate IL15 expression, which helps to further explain the abnormal IL-15 expression in MG patients and the pathogenesis of MG.

Stroke caused by atherosclerosis remains a leading cause of morbidity and mortality worldwide, associated with carotid plaque rupture and inflammation progression. However, the inflammatory biomarkers which aid in predicting the future course of plaques are less detailed. The present study investigated the association between plaque vulnerable and inflammatory biomarkers using blood and plaque specimens. Carotid plaque specimens were obtained from 80 patients following stroke, 14 patients suffering from transient ischaemic attack and 17 asymptomatic patients that underwent carotid endarterectomy. To assess changes in plaque characteristics at histological levels, plaques were categorized by the time between the latest ischemic stroke and surgical intervention within 30, 30‑90, 90‑180 and over 180 days following stroke. Serum levels of inflammatory biomarkers interleukin (IL)‑6, IL‑10 and kinin B1 receptor (B1R) were measured by ELISA. Histological assessment of plaque was used to evaluate the plaque stability, progression and the inflammatory biomarker levels. Comparisons of histological characteristics demonstrated that plaques revealed an unstable phenotype following stroke within 30, 30‑90 days and then remodeled into more stable plaques following stroke at 90‑180 and over 180 days. By comparing the serum levels of inflammatory biomarkers, it was observed that IL‑6 and B1R levels tended to decline whereas IL‑10 levels increased in stroke patients from

There is increasing evidence showing that inflammation occurs in atherosclerosis and contributes to the formation of atherosclerotic plaques. As important inflammatory peptides, kinins are increased in inflammation, eliciting vasodilation, increasing vascular permeability and recruiting inflammatory cells to the injury sites by activating specific receptors, B1 and B2. The two receptors have been reported to increase in inflammation, but their expressions remain to be defined in human carotid atherosclerotic plaques (CAP). In order to assess the gene expression of kinin receptors in human CAP, 47 CAP specimens were collected from patients undergoing endarterectomy and classified into stable and unstable plaque groups, respectively, with 10 mesenteric arteries used as controls. Total mRNA of B1R and B2R was extracted from CAPs and their levels were determined using reverse transcription-polymerase chain reaction. The expression of B1R and B2R mRNA was significantly upregulated in human CAPs compared to the control arteries. In the unstable plaques, the ratios of B1R to the β-actin mRNA level were significantly increased relative to the stable plaques. However, no notable differences were observed in the ratios of B2R to β-actin in mRNA expression between the stable and unstable plaques. The present study suggests that kinin-mediated inflammation involves the formation of atherosclerotic plaque and B1R plays an important role in plaque instability, indicating that kinin receptors can be used as potential targets for future therapeutic interventions.

Background Whether patients presenting with mild stroke should or should not be treated with intravenous rtPA is still controversial. This systematic review aims to assess the safety and outcome of thrombolysis in these patients. Material/Methods We systematically searched PubMed and Cochrane Central Register of Controlled Trials for studies evaluating intravenous rtPA in patients with mild or rapidly improving symptoms except case reports. Excellent outcome (author reported, mainly mRS 0-1), symptomatic intracranial hemorrhage (sICH) and mortality were analyzed. Results Fourteen studies were included (n=1906 patients). Of these, 4 studies were comparative (2 randomized and 2 non-randomized). The remaining were single-arm studies. On the basis of 4 comparative studies with a total of 1006 patients, the meta-analysis did not identify a significant difference in the odds of excellent outcome (OR=0.86; 95% CI: 0.64–1.15; I2=0) between IV rtPA-treated minor stroke and those without rtPA treatment. Eleven studies involving 1083 patients showed the pooled rate of excellent outcome was 76.1% (95% CI: 69.8–81.5%, I2=42.5). Seven studies involving 378 patients showed the mortality rate was 4.5% (95% CI: 2.6–7.5%, I2=1.4). Twelve studies involving 831 patients showed the pooled rate of sICH was 2.4% (95% CI: 1.5–3.8, I2=0). Conclusions Although efficacy is not clearly established, this study reveals the adverse event rates related to thrombolysis are low in mild stroke. Intravenous rtPA should be considered in these patients until more RCT evidence is available.

Bithalamic infarctions initially presenting as a convulsive seizure are rarely reported and, to our best knowledge, have never been reported in China. Here, we present a patient with convulsive seizure at the onset of bilateral paramedian thalamic infarction. The diffusion-weighted imaging revealed that the infarct area is supplied by Percheron artery. Associated with the relationship between seizure and centrencephalic system and reticular formation as previously reported, we suggest that seizure could be the onset symptom of paramedian thalamic infarction. Physicians should recognize this condition, because both seizure control and early ischemic stroke management are required.

Ischemic edema can alter the structure and permeability of the blood-brain barrier. Recent studies have reported that progesterone reduces cerebral edema after cerebral ischemia. However, the underlying mechanism of this effect has not yet been elucidated. In the present study, progesterone effectively reduced Evans blue extravasation in the ischemic penumbra, but not in the ischemic core, 48 hours after cerebral ischemia in rats. Progesterone also inhibited the down-regulation of gene and protein levels of occludin and zonula occludens-1 in the penumbra. These results indicate that progesterone may effectively inhibit the down-regulation of tight junctions, thereby maintaining the integrity of the blood-brain barrier and reducing cerebral edema.