Effects of KLF11 on Vascular Smooth Muscle Cells and its Underlying Mechanisms in Intracranial Aneurysm.

Vascular smooth muscle cells (VSMCs) affect the phenotypic changes in intracranial aneurysm (IA). They exhibit enhanced dissociation and migration and play a key role in IA pathogenesis. KLF transcription factor 11 (KLF11), a member of the KLF family, significantly affects the cancer cell proliferation, differentiation, and apoptosis. However, its expression, biological functions, and latent action mechanisms in IA remain unclear. This study aimed to analyze the effects of KLF11 on H2O2-induced human brain VSMCs (HBVSMCs) in IA. We determined the mRNA levels of KLF11 in 15 paired arterial wall tissues of patients with IA and healthy volunteers. HBVSMCs were stimulated with H2O2 for 6 h to establish an IA model in vitro. Cell viability, apoptosis, and inflammatory cytokine (interleukin [IL-1ß, tumor necrosis factor-α, and IL-6) levels were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide, flow cytometry, and enzyme-linked immunosorbent assays, respectively. KLF11 expression was determined via quantitative reverse transcription-polymerase chain reaction, western blotting, and immunofluorescence analyses. Furthermore, p-p38, p38, cleaved-caspase 3, and caspase 3 levels were determined via western blotting. KLF11 levels were downregulated in the arterial wall tissues of patients with IA than in those of the control group. KLF11 upregulation by KLF11-plasmid promoted the cell viability, reduced apoptosis, decreased cleaved-caspase 3 expression, and inhibited the secretion of inflammatory factors in H2O2-induced HBVSMCs. KLF11-plasmid remarkably reduced p-p38 expression and p-p38/p-38 ratio; however, these effects were reversed by P79350 treatment. Overall, KLF11 upregulation improved the HBVSMC functions and exerted protective effects against IA, suggesting its potential for IA treatment.

Hypoxia damages endothelial cell angiogenic function by reducing the Ca2+ restoring ability of the endoplasmic reticulum.

The angiogenic function of endothelial cells (ECs) is very important to tissues and organs that suffer from hypoxic injury. Exploring the role of endoplasmic reticulum (ER) Ca2+ homeostasis in angiogenesis under hypoxic conditions may provide new insight into the development of novel therapeutic approaches. Our research project evaluated the damaging effect of hypoxia on ER Ca2+ homeostasis in ECs during angiogenesis. Human umbilical vein endothelial cells (HUVECs) were isolated from the umbilical cord. We applied cobalt (II) chloride (CoCl2) to mimic hypoxic conditions. Changes in the angiogenic function of HUVECs under hypoxic conditions were evaluated. Dynamic changes in ER and cytosolic (Cyto) Ca2+ and reactive oxygen species (ROS) signalling were detected. In addition, Western blotting (WB) was performed to evaluate the expression levels of related proteins under different conditions. Treatment of HUVECs with 100 µM CoCl2 for 4 h successfully mimicked hypoxia and induced the generation of ROS signals. Processes related to HUVEC angiogenic function, including cell viability, tube formation, and migration, were significantly inhibited under hypoxic conditions. During these processes, Ca2+ was released from the ER of HUVECs and extracellular Ca2+ entered the cells, which resulted in Cyto Ca2+ overloading. The WB results showed that mimicking hypoxia increased AMPK-pAMPK activity. Hypoxic conditions also reduced the Ca2+ restoration ability of the ER by decreasing sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) expression and PLN phosphorylation. HUVEC angiogenic function can be disrupted under hypoxic conditions by decreasing Ca2+ restoration by the ER. This may provide new insight for the future development of novel therapies. However, the detailed mechanism requires further research.

Endoscopic Lateral and Superior Cerebellar Keyhole Approach to the Anterior and Middle Incisural Space and Meckel Cave: An Anatomic Study.

OBJECTIVE: We sought to assess the feasibility of endoscopic lateral and superior cerebellar keyhole approach for exposure of the anterior and middle incisural space and Meckel cave. METHODS: The endoscopic lateral and superior cerebellar keyhole approach was performed in 6 cadaveric heads (12 sides) using 0- and 30-degree endoscopes, respectively. The anatomic structures for this approach to the anterior and middle incisural space and Meckel cave were observed. RESULTS: By grinding out the suprameatal tubercle and petrous apex and incising the tentorium, the anatomic structures in the anterior incisural space were visualized. The mean area exposed with a 0-degree endoscope in the anterior incisural space was 212.50 ± 6.04 mm2, significantly less than that exposed with a 30-degree endoscope (233.83 ± 8.72 mm2) (P < 0.05). The anatomic distance of the Meckel cave in the depth was the same between a 0-degree endoscope and a 30-degree endoscope; however, the distance in the width was 9.48 and 12.32 mm, respectively (P < 0.01). The area of petrous window grinded by a 30-degree endoscope was only increased by 5.83 mm2, compared with a 0-degree endoscope (P > 0.05). CONCLUSIONS: This approach provides access to the anterior and middle incisural space and Meckel cave, which is feasible to clearly expose the anatomic structures in those regions with minimal invasiveness. Additionally, better visualization and surgical space can be achieved under a 30-degree endoscope.

Wrap-Clipping for Patients with Ruptured Blood Blister-Like Aneurysms of the Internal Carotid Artery: Case Series and Literature Review.

OBJECTIVE: Blood blister-like aneurysms (BBAs) of the internal carotid artery (ICA) are challenging to treat. We assessed the clinical and radiologic outcomes in patients with ruptured BBAs of the ICA treated with wrap-clipping. METHODS: From November 2016 to January 2020, the clinical and radiologic data of patients with subarachnoid hemorrhage (SAH) caused by ICA BBAs who underwent wrap-clipping were retrospectively analyzed. The clinical outcomes were evaluated according to the modified Rankin Scale (mRS). Radiologic follow-up examinations included digital subtraction angiography (DSA), computed tomography angiography (CTA), and magnetic resonance angiography (MRA). RESULTS: Seven patients were enrolled in this study. All BBAs were wrap-clipped successfully, including two BBAs that exhibited intraoperative bleeding and required balloon-assistance during surgery. All patients had favorable clinical outcomes during follow-up. Among the six patients who completed the radiologic follow-up visit, one patient presented ICA occlusion at the 6-month DSA follow-up, but no neurologic dysfunction was noted. We did not observe the progression of ICA stenosis in other patients. CONCLUSION: All BBAs in this study were wrap-clipped successfully and completely occluded. Wrap-clipping is effective for BBAs of the ICA and has favorable clinical outcomes. A multicenter study with a large sample size and a longer radiologic follow-up is necessary.