Decreased PDLIM1 expression in endothelial cells contributes to the development of intracranial aneurysm.

INTRODUCTION: Intracranial aneurysm (IA) is a common vascular enlargement that occurs in the wall of cerebral vessels and frequently leads to fatal subarachnoid hemorrhage. PDZ and LIM domain protein 1 (PDLIM1) is a cytoskeletal protein that functions as a platform for multiple protein complex formation. However, whether PDLIM is involved in the pathogenesis of IA remains poorly understood. METHODS: Loss-of-function and gain-of-function strategies were employed to determine the in vitro roles of PDLIM1 in vascular endothelial cells (VECs). A rat model of IA was generated to study the role of PDLIM1 in vivo. Gene expression profiling, Western blotting, and dual luciferase reporter assays were performed to uncover the underlying cellular mechanism. Clinical IA samples were used to determine the expression of PDLIM1 and its downstream signaling molecules. RESULTS: PDLIM1 expression was reduced in the endothelial cells of IA and was regulated by Yes-associated protein 1 (YAP1). Genetic silencing of PDLIM1 inhibited the viability, migratory ability, and tube formation ability of VECs. Opposite results were obtained by ectopic expression of PDLIM1. Additionally, PDLIM1 overexpression mitigated IA in vivo. Mechanistic investigations revealed that PDLIM1 promoted the transcriptional activity of ß-catenin and induced the expression of v-myc myelocytomatosis viral oncogene homolog (MYC) and cyclin D1 (CCND1). In clinical settings, reduced expression of PDLIM1 and ß-catenin downstream target genes was observed in human IA samples. CONCLUSION: Our study indicates that YAP1-dependent expression of PDLIM1 can inhibit IA development by modulating the activity of the Wnt/ß-catenin signaling pathway and that PDLIM1 deficiency in VECs may represent a potential marker of aggressive disease.

Left middle cerebral artery M1-2 segment dissecting aneurysm resection and reanastomosis under double-barrel STA-MCA bypass protection.

BACKGROUND: Middle cerebral artery (MCA) M1-related dissecting aneurysms involving the M1 segment are difficult because of the involvement of M1 perforators and the short duration of ischemia tolerance during bypass. METHOD: We report a case of MCA M1-2 dissecting aneurysm resection and reanastomosis under bypass blood flow protection. Histological staining was used to show aneurysm pathological characteristics. CONCLUSION: This case demonstrates the value of distal bypass for blood flow protection in MCA M1-2 dissecting aneurysm dissection and reanastomosis. Pathological staining showed intramural thrombus, cell dysfunction, microtube formation, and obvious inflammation.

How I do it: left posterior cerebral artery P1-2 segment dissecting aneurysm distal clipping via an A1-RAG-P2 bypass.

BACKGROUND: Posterior cerebral artery (PCA) P1-2 segment dissecting aneurysms are difficult because regular craniectomy aneurysm clipping or intravascular interventional therapy is not applicable. METHOD: We report distal clipping of a PCA P1-2 segment dissection aneurysm with an anterior cerebral artery (ACA) A1-radial artery graft-PCA P2 bypass. CONCLUSION: This case demonstrates the value of an ACA-RAG-PCA bypass in the therapy of a PCA dissecting aneurysm.

A heparin-rosuvastatin-loaded P(LLA-CL) nanofiber-covered stent inhibits inflammatory smooth-muscle cell viability to reduce in-stent stenosis and thrombosis.

BACKGROUND: An endovascular covered-stent has unique advantages in treating complex intracranial aneurysms; however, in-stent stenosis and late thrombosis have become the main factors affecting the efficacy of covered-stent treatment. Smooth-muscle-cell phenotypic modulation plays an important role in late in-stent stenosis and thrombosis. Here, we determined the efficacy of using covered stents loaded with drugs to inhibit smooth-muscle-cell phenotypic modulation and potentially lower the incidence of long-term complications. METHODS: Nanofiber-covered stents were prepared using coaxial electrospinning, with the core solution prepared with 15% heparin and 20 µM rosuvastatin solution (400: 100 µL), and the shell solution prepared with 120 mg/mL hexafluoroisopropanol. We established a rabbit carotid-artery aneurysm model, which was treated with covered stents. Angiography and histology were performed to evaluate the therapeutic efficacy and incidence rate of in-stent stenosis and thrombosis. Phenotype, function, and inflammatory factors of smooth-muscle cells were studied to explore the mechanism of rosuvastatin action in smooth-muscle cells. RESULT: Heparin-rosuvastatin-loaded nanofiber scaffold mats inhibited the proliferation of synthetic smooth-muscle cells, and the nanofiber-covered stent effectively treated aneurysms in the absence of notable in-stent stenosis. Additionally, in vitro experiments showed that rosuvastatin inhibited the smooth-muscle-cell phenotypic modulation of platelet-derived growth factor-BB induction and decreased synthetic smooth-muscle-cell viability, as well as secretion of inflammatory cytokines. CONCLUSION: Rosuvastatin inhibited the abnormal proliferation of synthetic smooth-muscle cells, and heparin-rosuvastatin-loaded covered stents reduced the incidence of stenosis and late thrombosis, thereby improving the healing rates of stents used for aneurysm treatment.

Validation of Wall Enhancement as a New Imaging Biomarker of Unruptured Cerebral Aneurysm.

Background and Purpose- High-resolution vessel wall magnetic resonance imaging is a promising technique for assessing wall structures of unruptured intracranial aneurysms (UIAs). However, the relationship between aneurysmal high-resolution vessel wall magnetic resonance imaging features and their histopathologic mechanism remains poorly understood. Methods- From February 2016 to February 2018, a total of 19 men and 28 women with 54 UIAs treated surgically were prospectively enrolled. The intraoperative observed gross pathology of the aneurysmal wall was compared with the enhancement features on high-resolution vessel wall magnetic resonance imaging. Specimens of the UIAs were harvested for histopathologic and immunohistochemistry analysis. Results- An irregular shape and large size was significantly related to UIA wall enhancement. Both uniform and focal wall enhancement may demonstrate the inflammation processes of UIA walls, although the latter may indicate more atherosclerotic plaque formation. Conclusions- Different high-resolution vessel wall magnetic resonance imaging enhancement features may represent variable inflammation status of a UIA wall, which may provide new insights into assessing the UIA wall structure and optimizing treatment.

Cyclic Mechanical Stretch Induced Smooth Muscle Cell Changes in Cerebral Aneurysm Progress by Reducing Collagen Type IV and Collagen Type VI Levels.

BACKGROUND/AIMS: Cerebral aneurysm growth is characterized by continuous structural weakness of local smooth muscle cells, though the mechanism is unclear. In this study, we examine protein changes in cerebral aneurysm and human brain vascular smooth muscle cells after cyclic mechanical stretch. We further explore the relationship between the smooth muscle cell changes and reductions in the levels of collagen types IV and VI. METHODS: Saccular cerebral aneurysms (n=10) were collected, and temporal artery samples were used as controls. Quantitative proteomics were analyzed and histopathological changes were examined. Smooth muscle cells were cultured in a flexible silicone chamber and subjected to 15% cyclic mechanical stretch. The effect of stretch on the cell viability, function, gene and protein expression were further studied for the understanding the molecular mechanism of aneurysm development. RESULTS: Proteomics analysis revealed 92 proteins with increased expression and 88 proteins with decreased expression compared to the controls (p<0.05). KEGG pathway analysis showed that the change in focal adhesion and extracellular matrix-receptor interaction, suggesting the involvement of collagen type IV and VI. The aneurysm tissue exhibited fewer smooth muscle cells and lower levels of collagen type IV and VI. Human brain vascular smooth muscle cell culture showed spindle-like cells and obvious smooth muscle cell layer. Cell proteomics analysis showed that decreased expression of 118 proteins and increased expression of 32 proteins in smooth muscle cells after cyclic mechanical stretch. KEGG pathway analysis indicated that focal adhesion and ECM-receptor interaction were involved. After cyclic mechanical stretch, collagen type IV and IV expression were decreased. Moreover, the stretch induced MMP-1 and MMP-3 expression elevation. CONCLUSION: We demonstrated that collagen type IV and VI were decreased in cerebral aneurysms and continuous cyclic mechanical stretch induced smooth muscle cell changes. Smooth muscle cell protection provides an additional therapeutic option to prevent the growth of cerebral aneurysms.

MicroRNA-137 and microRNA-195* inhibit vasculogenesis in brain arteriovenous malformations.

OBJECTIVE: Brain arteriovenous malformations (AVMs) are the most common cause of nontraumatic intracerebral hemorrhage in young adults. The genesis of brain AVM remains enigmatic. We investigated microRNA (miRNA) expression and its contribution to the pathogenesis of brain AVMs. METHODS: We used a large-scale miRNA analysis of 16 samples including AVMs, hemangioblastoma, and controls to identify a distinct AVM miRNA signature. AVM smooth muscle cells (AVMSMCs) were isolated and identified by flow cytometry and immunohistochemistry, and candidate miRNAs were then tested in these cells. Migration, tube formation, and CCK-8-induced proliferation assays were used to test the effect of the miRNAs on phenotypic properties of AVMSMCs. A quantitative proteomics approach was used to identify protein expression changes in AVMSMCs treated with miRNA mimics. RESULTS: A distinct AVM miRNA signature comprising a large portion of lowly expressed miRNAs was identified. Among these miRNAs, miR-137 and miR-195* levels were significantly decreased in AVMs and constituent AVMSMCs. Experimentally elevating the level of these microRNAs inhibited AVMSMC migration, tube formation, and survival in vitro and the formation of vascular rings in vivo. Proteomics showed the protein expression signature of AVMSMCs and identified downstream proteins regulated by miR-137 and miR-195* that were key signaling proteins involved in vessel development. INTERPRETATION: Our results indicate that miR-137 and miR-195* act as vasculogenic suppressors in AVMs by altering phenotypic properties of AVMSMCs, and that the absence of miR-137 and miR-195* expression leads to abnormal vasculogenesis. Ann Neurol 2017;82:371-384.

Interposition Intracranial-Intracranial Bypass Based on Anterior Cerebral Artery A1 Donor Anastomosis: Technical Advances, Outcomes, and Literature Review.

BACKGROUND: The bypass technique is important for treating complex intracranial aneurysms and is infrequently performed. Intracranial-intracranial (IC-IC) bypass has shown many advantages in recent years. OBJECTIVE: To review the techniques and outcomes of bypass based on anterior cerebral artery (ACA) A1 donor anastomosis in patients with intracranial aneurysm. METHODS: We retrospectively reviewed the clinical and imaging data, surgical strategy, and follow-up outcomes of 7 patients treated from 2019 to 2022. Neurological function was assessed by the modified Rankin Scale (mRS). A literature review was performed using PubMed. RESULTS: All 7 patients (3 male patients and 4 female patients; mean age, 50.4 ± 15.5 years) underwent aneurysm trapping or clipping using interposition IC-IC bypass based on ACA-A1 donor anastomosis. There were 6 middle cerebral artery (MCA) aneurysms and 1 posterior cerebral aneurysm in the series. One IC-IC bypass failed and was changed to extracranial-intracranial bypass. Three patients with MCA M1 aneurysm showed perforator-related infarction after the operation. The modified Rankin Scale score was 0 in 4 patients, 2 in 2 patients, and 1 in 1 patient. The long-term graft patency rate was 100%. CONCLUSION: Interposition IC-IC bypass based on ACA-A1 donor anastomosis provides an effective way to achieve blood flow reconstruction in the treatment of complex aneurysms. This technique provides better caliber and volume compatibility and diminishes neck incision. Perforator-related infarction was the main complication because of involvement of the MCA M1 aneurysm location. Proximal clipping is preferred to avoid perforator-related infarction.

The application of high-resolution vessel wall imaging in the in situ bypass surgeries for complex anterior cerebral artery aneurysms.

OBJECTIVE: Complex anterior cerebral artery (ACA) aneurysms are still technically challenging to treat. Bypass surgery is needed to achieve aneurysm obliteration and ACA territory revascularization. Severe atherosclerosis of aneurysm walls can cause clip slippage, intraoperative rupture, postoperative ischemic events. How to assess the atherosclerotic changes in vascular walls by high-resolution vessel wall magnitude resonance imaging (VWI) is the key question in complex ACA aneurysm surgical management. METHODS: This retrospective single-center study included eight patients diagnosed with complex anterior cerebral arteries admitted to our hospital for bypass surgery from January 2019 to April 2022. We discussed the application of VWI in aneurysms treated with in situ bypass and reviewed previous experience of revascularization strategies for complex ACA aneurysms. RESULTS: In this study, we treated 8 cases of complex ACA aneurysms (3 communicating aneurysms/5 postcommunicating aneurysms) over the prior one year. In situ side-to-side anastomosis (1 A2-to-A2/6 A3-to-A3) was performed in seven cases, and trapping combined with excision was performed in another case. Following bypass, complete trapping was performed in 4 cases, and proximal clipping was performed in 3 cases. No surgery-related neurological dysfunctions were observed. The final modified Rankin scale was 0 in seven of the eight cases and 2 in one case. CONCLUSION: High-resolution VWI, as a favorable preoperative assessment tool, provides insight into patient-specific anatomy and microsurgical options before operations, which can help neurosurgeons develop individualized and valuable surgical plans.

Association of Preoperative Vascular Wall Imaging Patterns and Surgical Outcomes in Patients With Unruptured Intracranial Saccular Aneurysms.

BACKGROUND: MR vascular wall imaging (VWI) may have prognostic value in patients with unruptured intracranial aneurysms (UIAs). OBJECTIVE: To evaluate the value of VWI as a predictor of surgical outcome in patients with UIAs. METHODS: This prospective cohort study evaluated surgical outcomes in consecutive patients with UIAs who underwent surgical clipping at a single center. All participants underwent high-resolution VWI and were followed for at least 6 months. The primary clinical outcome was modified Rankin scale (mRS) score 6 months after surgery. RESULTS: The number of patients in the no wall enhancement, uniform wall enhancement (UWE), and focal wall enhancement (FWE) groups was 37, 145, and 154, respectively. Incidence of postoperative complications was 15.5% in the FWE group, 12.4% in the UWE group, and 5.4% in the no wall enhancement group. The proportion of patients with mRS score >2 at the 6-month follow-up was significantly higher in the FWE group than in the UWE group (14.3% vs 6.9%; P = .0389). In the multivariate analysis, FWE (odds ratio, 2.573; 95% CI 1.001-6.612) and positive proximal artery remodeling (odds ratio, 10.56; 95% CI 2.237-49.83) were independent predictors of mRS score >2 at the 6-month follow-up. CONCLUSION: Preoperative VWI can improve the surgeon's understanding of aneurysm pathological structure. Type of aneurysmal wall enhancement on VWI is associated with clinical outcome and incidence of salvage anastomosis and surgical complications.

Resveratrol inhibits cerebral aneurysms in mice via downregulating the NF-κB pathway.

OBJECTIVES: Cerebral aneurysm (CA) is one of the most common cerebrovascular diseases. The study was conducted to investigate the effect of resveratrol (RES) on the CA formation and its possible mechanisms. MATERIALS AND METHODS: Murine model of CA was constructed by induced hypertension and fed without (model group) or with RES (RES group). A Sham group was used as a control. The CA formation and inflammatory response were examined morphologically and histochemically. The expression of nuclear factor-κB (NF-κB), matrix metalloproteinase (MMP)-2, and MMP-9 was analyzed using qRT-PCR and Western blots. RESULTS: CA was induced in mice after the left common carotid artery was ligated and fed with high sodium chloride. Compared with the model, mice fed with RES had significantly fewer CA with smaller size, normal thickness of the arterial wall (P<0.05), and fewer infiltrated macrophages in the aneurysm wall (P<0.05). qRT-PCR and Western blot analyses showed that the expression of MMP-2, MMP-9 and NF-κB was significantly elevated in the model as compared with the control and significantly decreased after RES treatments (P<0.05). CONCLUSIONS: RES can inhibit the CA formation in mice subjected to induced hypertension and this inhibition is likely mediated via downregulating the NF-κB pathway.

The Vascular Architecture of Cavernous Sinus Dural Arteriovenous Fistula and Its Impact on Endovascular Treatment Approach Selection and Outcome.

BACKGROUND: A cavernous sinus (CS) dural arteriovenous fistula (DAVF) is a form of abnormal arteriovenous communication that can be treated with endovascular embolization. Establishing an optimal access route should be based on vascular architecture. We reviewed 64 patients with CS-DAVF who underwent endovascular embolization and report the endovascular treatment approach selection and outcome. METHODS: Clinical data were obtained from 64 patients with CS-DAVF who had been surgically treated at the authors' hospital between 2009 and 2022. Patients' medical records, imaging data, and follow-up outcomes were retrospectively analyzed. RESULTS: All 64 patients (15 male, 49 female; mean age, 50 years) underwent CS-DAVF embolization. The most common symptoms were exophthalmos (39.1%), chemosis (35.9%), and headache (28.1%). On digital subtraction angiography images, 34.4% of the DAVFs were unilateral, and 82.8% were fed by both the external carotid artery and internal carotid artery. Of the patients' inferior petrosal sinuses (IPSs), 54.7% were nonopacified. The most common intravascular approaches included trans-IPS (37.5%) and trans-artery (28.1%) approaches. More than half of the CS-DAVFs were embolized by both coils and Onyx (62.5%). A total of 85.9% of the fistulas were completely embolized, and the follow-up rate was 76.6%. The modified Rankin Scale score was 0.9 ± 1.0. CONCLUSIONS: The vascular architecture of CS-DAVF is closely related to endovascular treatment approach selection and outcome. Combined with the modified IPS recanalization technique, the trans-IPS approach is the safest and most effective approach. Dual microcatheter and balloon assistance techniques ensure the safety and completeness of embolization.

Microsurgical treatment of posterior inferior cerebellar aneurysms based on angioarchitecture supplemented by high-resolution vessel wall MRI: a case series report.

BACKGROUND: Surgical treatment of posterior inferior cerebellar artery (PICA) aneurysms is challenging because many are nonsaccular and atherosclerotic. We report our tailored approach to PICA aneurysms, which is based on angioarchitecture supplemented by high-resolution vessel wall MRI (HR-VW MRI) findings. METHODS: From March 2010 to September 2020, 27 patients with 29 PICA aneurysms underwent surgical treatment in our institution. Since October 2016, HR-VW MRI has been used for aneurysmal wall assessment. Clinical characteristics, radiological data and surgical outcomes were analysed. RESULTS: Nineteen proximal PICA aneurysms (vertebral artery (VA), P1, P2 and P3) were treated using the far-lateral approach. Ten distal PICA aneurysms (P4, P5) were treated using the suboccipital midline approach. Direct clipping or clip reconstruction was achieved in 19 aneurysms. Ten were trapped in conjunction with extracranial-intracranial or intracranial-intracranial bypass, including three occipital artery-PICA reimplantations, three PICA-VA reimplantations, two PICA-PICA side-to-side anastomoses, one PICA-PICA reimplantation and one PICA-PICA reanastomosis. All aneurysms were eventually completely obliterated and all bypasses remained patent. At the last follow-up, 26 patients (96.2%) achieved a good outcome (modified Rankin Scale score <3). Eight patients underwent HR-VW MRI. Among these, the six aneurysms with focal wall enhancement required bypass and the two with negative enhancement were successfully clipped. CONCLUSION: PICA aneurysms have a higher frequency of complex features such as large or giant size and fusiform or dissecting morphology. Favourable outcomes were achieved with individualised microsurgical strategies based on angioarchitecture. HR-VW MRI may be used as a promising technique to predict aneurysmal atherosclerosis.

miR-139-5p Suppresses Proliferation and Angiogenesis of Intracranial Aneurysm via FGB.

Intracranial aneurysm (IA) is a common cerebrovascular disease. Understanding the mechanism regulating the progression of IA could help to develop novel therapeutic methods for this disease. In this study, we confirmed FGB is one of the targets of miR-139-5p. Moreover, miR-139-5p expression in intracranial aneurysm specimens was suppressed compared with normal tissues. However, we found that FGB in intracranial aneurysm samples was remarkedly enhanced compared to normal tissues. Moreover, we found miR-139-5p overexpression and FGB silencing inhibit HBMEC proliferation and tube formation and suppressed α-SMA and CXCR4 levels in HBMEC cells. Furthermore, a rescue experiment confirmed miR-139-5p affected the proliferation and angiogenesis of HBMEC through FGB. Despite further research being needed to determine the exact functions of miR-139-5p in the formation of CA, our new findings contribute to a comprehensive understanding of the treatment mechanism of IA.

Cavernoma-Associated Epilepsy Within the Mesial Temporal Lobe: Surgical Management and Seizure Outcome.

OBJECTIVE: We sought to explore a treatment protocol for patients with mesial temporal cerebral cavernoma (MTC)-associated epilepsy. METHODS: All MTC-associated epilepsy patients admitted to our center between January 2005 and December 2013 were analyzed. Seizure outcome for each presurgical epilepsy type was reported. The modified Engel classification was used to assess outcome. The neurologic outcome was scored by the modified Rankin Scale. RESULTS: Fifty-three patients admitted to the center were seen by a functional electrocortigraphy (ECoG group) or vascular (non-ECoG group) neurosurgery team. There were 21 patients with drug-resistant epilepsy (DRE), 20 patients with chronic epilepsy (CE), and 12 patients with sporadic epilepsy (SE). The neurovascular team treated 37 (69.8%) patients, and the ECoG group treated 16 (30.2%) patients. All patients underwent a mean follow-up of 106.5 ± 29.1 months. Almost all SE patients (11/12, 91.7%) in both teams achieved seizure-free status at follow-up. In the CE group, the long-term seizure-free probability among patients in the ECoG and non-ECoG groups was (66.7%) and (52.9%), respectively. DRE patients in the ECoG group had a lower seizure relapse rate after surgery than those who underwent non-ECoG surgery (P = 0.042). Fifty-two patients (98.1%) complained of postsurgery memory loss. Seizure outcome in the first postoperative year was a reasonable predictor of long-term outcome. CONCLUSIONS: A comprehensive preoperative and intraoperative assessment could help the patient with MTC-associated epilepsy choose a suitable surgical time and maximize the benefit between seizure control and cognition protection. The characters of intraoperative ECoG and postoperative seizure outcome at 1-year follow-up can predict a long-term epilepsy prognosis.

Pathology and Protein Changes of the Spinal Dural Arteriovenous Fistula Arterial Draining Vein Under Sustained High Vascular Pressure.

Object: Spinal dural arteriovenous fistula (SDAVF) is the most common spinal vascular shunt lesion. Although pathological changes in the SDAVF draining vein (SDAVF-DV) have been elucidated, protein changes remain enigmatic. We investigated the pathology and protein changes in the SDAVF-DV under sustained high vascular pressure. Methods: Three SDAVF-DV samples were compared with superficial temporal artery (STA) and superficial temporal vein (STV) samples as controls. Vascular structure was revealed by hematoxylin and eosin (H&E) and Masson staining; and cell distribution, extracellular matrix, and inflammation infiltration were observed by immunohistochemistry. Label-free quantitative proteomics was performed, and the peptide mixture was fractionated and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins. Bioinformatics analysis of the differentially expressed proteins was performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) networks. Results: H&E and Masson staining showed an artery-like structure of the SDAVF-DV. Immunostaining showed that vWF+ cells were not continuous in the SDAVF-DV. Although α-SMA+ and AT1+ cells were more abundant in the STV than in the SDAVF-DV, piezo-1 expression was lower in the SDAVF-DV. The SDAVF-DV showed different distributions of elastin, COL I, and COL III. COL IV and COL VI were decreased in the SDAVF-DV, while CD45+ cells and COX-1 were increased compared with those in the controls. No differences in CD68 expression and COX-2 staining were observed between the SDAVF-DV and controls. Compared with the STA, 95 proteins were upregulated and 303 proteins were downregulated in the SDAVF-DV. The most differential GO terms in each category were the adenylate cyclase-modulating G protein-coupled receptor signaling pathway, U6 snRNP, and SH3 domain binding. The most differentially expressed KEGG protein pathway was focal adhesion. Compared with the STV, the SDAVF-DV had 158 upregulated proteins and 362 downregulated proteins. The most differential GO terms in each category were lamellipodium assembly, U6 snRNP, and SH3 domain binding; and the most differentially expressed KEGG protein pathway was dilated cardiomyopathy. PPI analysis revealed PPIs among the top 300 proteins. Conclusions: The SDAVF-DV exhibits specific pathology and protein expression changes under sustained high vascular pressure. The results of the present study provide insights into the pathogenesis of SDAVF formation at the protein level as well as a scientific foundation for further exploration of the pathophysiological mechanism of the SDAVF.

Changes in the Small RNA Expression in Endothelial Cells in Response to Inflammatory Stimulation.

OBJECTIVE: Endothelial cell inflammation is a common pathophysiological process in many cardiovascular and cerebrovascular diseases. Small RNA is a kind of short nonprotein coding RNA molecule. Changes in the small RNA expression in endothelial cells have been linked to the development of cardiovascular and cerebrovascular diseases. We investigated and verified differentially expressed small RNAs in endothelial cells in response to inflammatory stimulation. METHODS: Primary rat endothelial cells were obtained from Sprague-Dawley rats and treated with 10 ng/ml TNF-α for 24 hours. Small RNA sequencing was used to generate extensive small RNA data. Significantly differentially expressed small RNAs identified in the analysis were further confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Then, we investigated the tissue-specific small RNA expression after RNA extraction from different tissues. RESULTS: Small RNA sequencing demonstrated that 17 miRNAs, 1 piRNA, 10 snoRNAs, and 7 snRNAs were significantly differentially expressed. qRT-PCR identified 3 miRNAs, 2 snoRNAs, and 2 snRNAs with significantly different expression. Analysis of the tissue-specific expression showed that rno-miR-126a-5p was predominantly expressed in the lung, rno-miR-146a-5p in the intestines, and rno-novel-178 in the heart. Rno-piR-017330 was mainly expressed in the muscle. snoR-8966.1 was predominantly expressed in the bone. snoR-6253.1 was mostly expressed in the vessels and bone. snR-29469.1 was mainly expressed in the bone, and snR-85806.1 was predominantly expressed in the vessels and bone. CONCLUSIONS: We report for the first time the expression of small RNAs in endothelial cells under inflammatory conditions. TNF-α can regulate the expression of small RNAs in endothelial cells, and their expression is tissue-specific.

Predicting the Poor Recovery Risk of Aneurysmal Subarachnoid Hemorrhage: Clinical Evaluation and Management Based on a New Predictive Nomogram.

PURPOSE: To develop and validate a model for identifying the risk factors of poor recovery in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: A prediction model was developed using training data obtained from 1577 aSAH patients from multiple centers. The patients were followed for 6 months on average and assessed using the modified Rankin Scale; patient information was collected with a prospective case report form. The least absolute shrinkage and selection operator regression were applied to optimize factor selection for the poor recovery risk model. Multivariable logistic regression, incorporating the factors selected in the previous step, was used for model predictions. Predictive ability and clinical effectiveness of the model were evaluated using C-index, receiver operating characteristic curve, and decision curve analysis. Internal validation was performed using the C-index, taking advantage of bootstrapping validation. RESULTS: The predictors included household income per capita, hypertension, smoking, migraine within a week before onset, Glasgow Coma Scale at admission, average blood pressure at admission, modified Fisher score at admission, treatment method, and complications. Our newly developed model made satisfactory predictions; it had a C-index of 0.796 and an area under the receiver operating characteristic curve of 0.784. The decision curve analysis showed that the poor recovery nomogram was of clinical benefit when an intervention was decided at a poor recovery threshold between 2% and 50%. Internal validation revealed a C-index of 0.760. CONCLUSION: Our findings indicate that the novel poor recovery nomogram may be conveniently used for risk prediction in aSAH patients. For patients with intracranial aneurysms, migraine needs to be vigilant. Quitting smoking and blood pressure management are also beneficial.

Comparative bioinformatics analysis between proteomes of rabbit aneurysm model and human intracranial aneurysm with label-free quantitative proteomics.

AIMS: This study aimed to find critical proteins involved in the development of intracranial aneurysm by comparing proteomes of rabbit aneurysm model and human aneurysms. METHODS: Five human intracranial aneurysm samples and 5 superficial temporal artery samples, and 4 rabbit aneurysm samples and 4 control samples were collected for protein mass spectrometry. Four human intracranial aneurysm samples and 4 superficial temporal artery samples, and 6 rabbit aneurysm samples and 6 control samples were used for immunochemistry. RESULTS: Proteomic analysis revealed 180 significantly differentially expressed proteins in human intracranial aneurysms and 716 significantly differentially expressed proteins in rabbit aneurysms. Among them, 57 proteins were differentially expressed in both species, in which 24 were increased and 33 were decreased in aneurysms compared to the control groups. Proteins were involved in focal adhesion and extracellular matrix-receptor interaction pathways. We found that COL4A2, MYLK, VCL, and TAGLN may be related to aneurysm development. CONCLUSION: Proteomics analysis provided fundamental insights into the pathogenesis of aneurysm. Proteins related to focal adhesion and extracellular matrix-receptor interaction pathways play an important role in the occurrence and development of intracranial aneurysm.

One-Stage Treatment in a Hybrid Operation Room to Cure Brain Arteriovenous Malformation: A Single-Center Experience.

OBJECTIVE: To report the principles and techniques of using a hybrid operation room in the treatment of brain arteriovenous malformation (BAVM). METHODS: From October 1, 2016 to December 31, 2018, we treated 54 consecutive patients with nonemergent BAVM in a hybrid operation room. The clinical data, radiologic images, and outcomes were collected to establish a prospective database for evaluation. RESULTS: Thirty-two male and 22 female patients were enrolled with a mean age of 32.6 ± 13.1 years (range, 10-61 years). Bleeding (n = 32, 59.3%) was the main clinical presentation, followed by headache (n = 27, 50.0%), seizures (n = 14, 25.9%), neurofunctional deficits (n = 16, 29.6%), and no symptoms (n = 2, 3.7%). Thirty-one patients (57.4%) accepted resection without intraoperative embolization, 18 (33.3%) were treated with combined embolization and resection, and 5 (9.3%) were cured with intraoperative embolization and resection was cancelled. All patients achieved total BAVM obliteration confirmed with intraoperative angiography. There were no significant differences in outcomes between low-grade (Spetzler-Martin grades I, II, and modified grade III-) and high-grade (Spetzler-Martin grades ≥IV and modified grade III+) groups, except that the high-grade group had more blood loss (667.9 ± 647.5 vs. 284.3 ± 148.6 mL; P = 0.046) and longer postoperative hospitalization (17.1 ± 9.1 vs. 10.8 ± 5.4 days; P = 0.026). At discharge, 52 patients (96.3%) had favorable outcomes (Glasgow Outcome Scale score ≥4). Forty-three patients (79.6%) received 1 year follow-up after treatment; 97.7% (n = 42) of these had ongoing favorable outcomes. However, 4 patients with low-grade BAVM had recurrence. CONCLUSIONS: The hybrid operation room can ensure safe, comprehensive treatment of BAVM, offering the opportunity for a favorable curative treatment in 1 stage.