BMSCs Regulate Astrocytes through TSG-6 to Protect the Blood-Brain Barrier after Subarachnoid Hemorrhage.

BACKGROUND: In patients with subarachnoid hemorrhage (SAH), the damage of the blood-brain barrier (BBB) can be life-threatening. Mesenchymal stem cells are widely used in clinical research due to their pleiotropic properties. This study is aimed at exploring the effect of BMSCs regulating astrocytes on the BBB after SAH. METHODS: The SAH model was established by perforating the blood vessels. BMSCs were transfected with TSG-6 inhibitor plasmid and cocultured with astrocytes. Intravenous transplantation of BMSCs was utilized to treat SAH rats. We performed ELISA, neurological scoring, Evans blue staining, NO measurement, immunofluorescence, BBB permeability, Western blot, HE staining, Nissl staining, and immunohistochemistry to evaluate the effect of BMSCs on astrocytes and BBB. RESULTS: SAH rats showed BBB injury, increased BBB permeability, and brain histological damage. BMSCs will secrete TSG-6 after being activated by TNF-α. Under the influence of TSG-6, the NF-κB and MAPK signaling pathways of astrocytes were inhibited. The expression of iNOS was reduced, while occludin, claudin 3, and ZO-1 expression was increased. The production of harmful substances NO and ONOO- decreased. The level of inflammatory factors decreased. The apoptosis of astrocytes was weakened. TSG-6 secreted by BMSCs can relieve inflammation caused by SAH injury. The increase in BBB permeability of SAH rats was further reduced and the risk of rebleeding was reduced. CONCLUSION: BMSCs can regulate the activation of astrocytes through secreting TSG-6 in vivo and in vitro to protect BBB.

Efficacy and Safety of Combined Endovascular Embolization and Stereotactic Radiosurgery for Patients with Intracranial Arteriovenous Malformations: A Systematic Review and Meta-Analysis.

Whether the use of endovascular embolization could provide additional benefits in patients treated with stereotactic radiosurgery (SRS) for intracranial arteriovenous malformations (IAVMs) remains controversial. The current meta-analysis was conducted to assess the efficacy and safety of SRS with and without prior endovascular embolization in patients with IAVMs. The electronic databases of PubMed, EmBase, and Cochrane Library were systematically searched for eligible studies published from inception to August 12, 2020. The pooled results for obliteration rate, rehemorrhage rate, and permanent neurological deficits were calculated by odds ratios (ORs) with 95% confidence intervals (CIs) using the random-effects model. The sensitivity analysis, subgroup analysis, and publication bias for investigated outcomes were also evaluated. Nineteen studies (two prospective and 17 retrospective studies) involving a total of 3,454 patients with IAVMs were selected for the final meta-analysis. We noted that prior embolization and SRS were associated with a lower obliteration rate compared with SRS alone (OR, 0.57; 95% CI, 0.44-0.74; P < 0.001). However, prior embolization and SRS were not associated with the risk of rehemorrhage (OR, 1.05; 95% CI, 0.81-1.34; P = 0.729) and permanent neurological deficits (OR, 0.80; 95% CI, 0.48-1.33; P = 0.385) compared with SRS alone. The sensitivity analysis suggested that prior embolization might reduce the risk of permanent neurological deficits in patients with IAVMs treated with SRS. The treatment effects of prior embolization in patients with IAVMs could be affected by nidus volume, margin dose, intervention, and follow-up duration. This study found that prior embolization was associated with a reduced risk of obliteration in patients with IAVMs treated with SRS. Moreover, prior embolization might reduce the risk of permanent neurological deficits in patients with IAVMs.

Involvement of TLR2/4­MyD88­NF­κB signaling pathway in the pathogenesis of intracranial aneurysm.

Toll­like receptor (TLR) 2/4 serves an important regulatory role in nerve tissue injury. However, the downstream and potential mechanisms remain to be elucidated. The present study was designed to investigate the roles of the TLR2/4­major myeloid differentiation response gene 88 (MyD88)­NF­κB signaling pathway in the development of intracranial aneurysm. The expression of TLR2, TLR4 and MyD88 in the blood of normal controls and patients with intracranial aneurysm were detected by quantitative PCR and ELISA. Human brain vascular smooth muscle cells were treated by Angiotensin II (Ang II) to evaluate the involvement of TLR2/4­MyD88­NF­κB signaling pathway in the process. The in vitro experiment was divided into four groups: The control group, an Ang â…¡ group, an Ang â…¡ + small interfering (si)RNA control group and an Ang â…¡ + TLR2­group. Cell viability, migration, apoptosis and expression of TLR2, TLR4, MyD88, NF­κB and phosphorylated (p­)p65 expression were detected. The results demonstrated that the expression of TLR2, TLR4, MyD88 and NF­κB at mRNA and protein levels in patients with intracranial aneurysm was significantly higher compared with corresponding protein in normal controls (P<0.05). In vitro experiments demonstrated that Ang â…¡ treatment increased the cell proliferation and migration rate but reduced the apoptotic rate compared with the control (P<0.05). The expression of TLR2, TLR4, MyD88, NF­κB and p­p65 was significantly increased in the Ang II group (vs. control; P<0.05). By contrast, TLR2­short interfering RNA reduced the cell proliferation and migration rate, and reduced the expression of TLR2, TLR4, MyD88, NF­κB and p­p65 (vs. Ang â…¡ + short interfering RNA control; P<0.05). In conclusion, the data of the present study indicated that the TLR2/4­MyD88­NF­κB signaling pathway is involved in the pathogenesis of intracranial aneurysm.

Long non-coding RNA LINC00525 regulates the proliferation and epithelial to mesenchymal transition of human glioma cells by sponging miR-338-3p.

Long non-coding RNA (LncRNA) LINC00525 has been shown to be upregulated in several human cancers and deduced to possess caner regulatory role. The regulation of molecular mechanics of human glioma by lncRNA-LINC00525 through microRNA sponging in glioma is elusive. The lncRNA-LINC00525 showed significant (P < 0.05) upregulation in glioma cancer cells. The upregulation of lncRNA-LINC00525 was upto 6.6-fold in glioma cells relative to the normal cells. Knockdown of lncRNA-LINC00525 significantly declined the proliferation of the glioma cancer cells. Additionally, the colony formation was inhibited by around 60% in glioma cells. The wound healing and transwell assays revealed significant (P < 0.05) inhibition of migration and invasion potential under lncRNA-LINC00525 knockdown. The western blotting study of biomarkers of epithelial to mesenchymal transition (EMT) revealed that lncRNA-LINC00525 gene silencing reduced the expression of mesenchymal molecular markers but increased the protein levels of epithelial markers. miR-338-3p was predicted to be interacting with lncRNA-LINC00525 in glioma and was shown to mediated the regulatory role of lncRNA-LINC00525. Taken together, the results of present study are supportive of the prognostic applicability of lncRNA-LINC00525 against human glioma together with its therapeutic potential against the said malignancy.

Neurosurgical Clipping versus Endovascular Coiling for Patients with Intracranial Aneurysms: A Systematic Review and Meta-Analysis.

OBJECTIVE: We compared the efficacy and safety of neurosurgical clipping with those of endovascular coiling for patients with intracranial aneurysm (IA) stratified by country, publication year, study design, sample size, mean age, percentage of male patients, percentage of aneurysms located in the anterior circulation, and follow-up duration. METHODS: We identified 64 studies (7 randomized controlled trials, 21 prospective cohort studies, and 36 retrospective studies) of clipping versus coiling for IA from PubMed, EmBase, and the Cochrane Library up to September 2019. RESULTS: No significant differences were found in the incidence of poor outcomes observed between clipping and coiling for patients with ruptured IAs. In contrast, the incidence of a poor outcome was significantly increased for unruptured IAs treated by clipping. Clipping was associated with a lower risk of mortality for ruptured IAs, although no significant differences were found between clipping and coiling for unruptured IAs. Clipping was associated with a lower risk of rebleeding for ruptured IAs and an increased risk of bleeding for unruptured IAs. When only randomized controlled trials were included in the analysis, patients with ruptured IAs treated by clipping had an increased incidence of poor outcomes compared with those treated by coiling. Clipping reduced the risk of hydrocephalus and incomplete occlusion and increased the rate of complete occlusion for ruptured IAs. No significant differences in the risk of ischemic infarct and vasospasm were found between clipping and coiling. CONCLUSIONS: Surgical clipping might be superior to endovascular coiling for ruptured IAs. However, clipping was associated with a greater incidence of poor outcomes and bleeding compared with coiling for unruptured IAs.