Surgical Clipping of Intracranial Aneurysms Using a Transcranial Neuroendoscopic Approach.

OBJECTIVE: This retrospective study was performed to evaluate the feasibility and safety of surgically clipping intracranial aneurysms using a transcranial neuroendoscopic approach. METHODS: A total of 229 patients with cerebral aneurysms were included in our study, all of whom were treated with clamping surgery at Wuhan University People's Hospital. They were divided into neuroendoscopic and microscopic groups, according to whether or not neuroendoscopy was used for the clamping surgery. We statistically analyzed the patients' baseline data, surgical outcomes, and complications, which were then evaluated to assess the treatment effect. RESULTS: The baseline characteristics were not statistically significant, except for gender, for which the proportions of female patients in the two groups were 69 (56.1%) and 46 (43.4%). There were no patients with incomplete aneurysm clamping or parent vessel occlusion in the neuroendoscopic group, and there were 4 (3.8%) and 2 (1.9%) in the microscopic group, respectively; however, there was no statistically significant difference in the comparison of the two groups. The mean operative times of the two groups were 181 min and 154 min, respectively, and were statistically different. However, the mRS scores of the two groups showed no significant difference in patient prognosis. The differences in complications (including limb hemiplegia, hydrocephalus, vision loss, and intracranial infection) were not statistically significant, except for cerebral ischemia, for which the proportions of patients in the two groups were 8 (6.5%) and 16 (15.1%). CONCLUSIONS: Neuroendoscopy can provide clear visualization and multi-angle views during aneurysm clipping, which is helpful for ensuring adequate clipping and preventing complications.

Ursolic Acid Alleviates Neuroinflammation after Intracerebral Hemorrhage by Mediating Microglial Pyroptosis via the NF-κB/NLRP3/GSDMD Pathway.

The neuroinflammatory response after intracerebral hemorrhage (ICH) causes a large amount of neuronal loss, and inhibiting the inflammatory response can improve the prognosis. In previous laboratory studies and clinical trials, ursolic acid (UA) inhibited the inflammatory response, but whether it can be administered to inhibit the neuroinflammatory response after cerebral hemorrhage is unknown. The aim of this study was to investigate the effects of ursolic acid after cerebral hemorrhage. Online databases were used to obtain potential therapeutic targets of ursolic acid for the treatment of cerebral hemorrhage, and possible mechanisms were analyzed by KEGG, GO, and molecular docking. A rat model of cerebral hemorrhage was established using collagenase, and an in vitro cerebral hemorrhage model was constructed by adding hemin to BV2 cell culture medium. Enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), immunofluorescence, TUNEL staining, and calcein/PI staining were used to investigate the degree of microglial M1 polarization, changes in the levels of inflammatory factors, activation of the NF-κB pathway, and changes in the indicators of cellular death after ursolic acid treatment. In addition, phorbol 12-myristate 13-acetate (PMA) was used to activate the NF-κB pathway to verify that ursolic acid exerts its anti-neuroinflammatory effects by regulating the NF-κB/NLRP3/GSDMD pathway. Network pharmacology and bioinformatics analyses revealed that ursolic acid may exert its therapeutic effects on cerebral hemorrhage through multiple pathways. Together, in vivo and in vitro experiments showed that ursolic acid inhibited microglial M1 polarization and significantly reduced the levels of p-NF-κB, GSDMD-N, cleaved caspase-1, TNF-α, IL-6, and IL-1ß, which were significantly inhibited by the use of PMA. Ursolic acid inhibits microglial pyroptosis via the NF-κB/NLRP3/GSDMD pathway to alleviate neuroinflammatory responses after cerebral hemorrhage.

BCL2A1 is associated with tumor-associated macrophages and unfavorable prognosis in human gliomas.

B-cell lymphoma 2-related protein A1 (BCL2A1) is a member of the BCL-2 family. Previous studies have shown that BCL2A1 is closely related to the tumorigenesis and resistance to chemotherapy of multiple solid tumors, such as breast cancer. However, the expression pattern and potential biological function of BCL2A1 in glioma remain unknown. For the first time, we found that the expression of BCL2A1 was higher in human glioma tissues than in normal brain tissues (NBTs) in both public datasets and an in-house cohort. High BCL2A1 expression was associated with advanced WHO grade, IDH 1/2 wild type and the mesenchymal (ME) subtype, and its overexpression in glioma predicted resistance to temozolomide (TMZ) chemotherapy and unfavorable prognosis. In addition, Gene set enrichment analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that BCL2A1 was significantly correlated with the immune response and immune-related pathways, and BCL2A1 expression was positively correlated with microenvironmental parameters (immune, stromal, and ESTIMATE scores) and macrophage infiltration. Interestingly, bioinformatic prediction and immunohistochemical/immunofluorescence staining analysis revealed that BCL2A1 expression was obviously associated with the tumor-associated macrophages (TAMs) markers CD68 and CCL2. Notably, knockdown of BCL2A1 significantly inhibited cell proliferation of U87 and U251 in vitro, induced smaller tumor size and prolonged survival time of mice in vivo. Co-culture experiments of macrophages and GBM cells showed that BCL2A1 knockdown inhibited macrophage migration. Meanwhile, knockdown of BCL2A1 was associated with low expression of CD68 and CCL2 in intracranial xenograft model. This may suggest that BCL2A1 promotes the progression of glioma and influences the prognosis of patients by participating in TAMs infiltration. In conclusion, these findings suggest that BCL2A1 could serve as a promising prognostic indicator and immunotherapy target in gliomas.

Post-operative rebleeding in patients with spontaneous supratentorial intracerebral hemorrhage: factors and clinical outcomes.

OBJECTIVE: To explore factors affecting postoperative rebleeding in patients with spontaneous supratentorial intracerebral hemorrhage (SSICH). METHODS: We retrospectively analyzed data from 724 patients with SSICH treated at Renmin Hospital of Wuhan University from December 2018 to October 2021. Finally, 294 people were eligible to be included in this study. Hematoma locations were classified as basal ganglia, thalamus, subcortex, or intraventricular. Surgery was categorized as neuroendoscopic surgery, burr hole (stereotactic drilling and drainage), or open craniotomy. Postoperative rebleeding was recorded. The incidence, risk factors, and prognosis of postoperative rebleeding were evaluated. RESULTS: All procedures were successfully completed. Postoperative rebleeding occurred in 57 patients (19.83%, 57/294). Univariate logistic regression analysis identified these risk factors for rebleeding: admission Glasgow Coma Scale (GCS) score, irregular hematoma morphology by preoperative Computed Tomography (CT), postoperative hypertension, hematoma location, surgical method (P<0.05), and preoperative hematoma volume (P<0.1). Multivariate logistic regression analysis confirmed admission GCS score, irregular hematoma morphology by preoperative CT, postoperative hypertension, hematoma location, and surgical method as significant risk factors (P<0.05). Burr hole surgery and basal ganglia hematomas were associated with increased odds of rebleeding, and the mortality rates in patients with rebleeding versus no rebleeding were 7.02% versus 0.84%. CONCLUSIONS: Neuroendoscopic surgery, craniotomy, and burr hole are all effective for treating SSICH, but burr hole surgery was an important risk factor for rebleeding and an adverse outcome. Admission GCS score, irregular hematoma morphology, blood pressure control, hematoma location, and surgical method are affected the risk of postoperative rebleeding. 3D Slicer-assisted neuroendoscopic surgery may be the most effective treatment for many patients with SSICH.

Perihematomal edema after minimally invasive surgery: a matter of concern to neurosurgeons.

The purpose of this study is to explore the evolution of brain edema after minimally invasive surgery in deep spontaneous cerebral hemorrhage (DSICH) treatment and to analyze the differences in edema after different surgical methods. The clinical data of 105 patients with DSICH treated at Renmin Hospital of Wuhan University from January 2020 to June 2022 were analyzed retrospectively. Among them, 54 patients were treated with minimally invasive puncture and drainage surgery (MIPDS group), and 51 were treated with neuroendoscopic surgery (NES group). Continuous computed tomography images of patients in the hospital and 3D Slicer software were used to quantitatively calculate the edematous area to explore the changes in perihematomal edema volume in the two groups after the operation. The peak volume of postoperative edema (37.36±10.51 mL) in the MIPDS group was more extensive than that in the NES group, and its net increase in edema volume was 16.86±10.01 mL more than that in the NES group. The relative edema index (0.86±0.26) was lower in the NES group than in the MIPDS group (P < 0.05). The peak of postoperative edema in the MIPDS group was at 6-8 days after the operation, and that in the NES group was most often at 3-5 days after the operation. There are differences in perihematomal edema of DSICH treated by different minimally invasive methods. Compared with the MIPDS group, the NES group showed earlier peak of cerebral edema and lower degree of cerebral edema. The absolute regression volume of edema in the MIDPs group was greater than that in the NEs group, but there was no difference in the regression rate of edema between the two groups.

TMEM2 induces epithelial-mesenchymal transition and promotes resistance to temozolomide in GBM cells.

Glioblastoma multiforme (GBM) is the most common intracranial malignant tumor and is notorious for its poor prognosis. An important element in the short overall survival of GBM patients is the lack of understanding the pathogenesis and progression of tumor and deficiency biomarkers that can be used for early diagnosis and therapeutic sensitivity monitoring. Studies have shown that transmembrane protein 2 (TMEM2) is participated in tumorigenesis of various human tumors, including rectal and breast cancers. Although Qiuyi Jiang et al. have reported that TMEM2 combined with IDH1/2 and 1p19q can predict the survival time of glioma patients based on bioinformatics, its expression and biological role of glioma remain unclear. In our study, we investigated the effect of TMEM2 expression level on glioma malignancy in public datasets and an independent internal dataset. We revealed TEMM2 expression was higher in GBM tissues than in non-tumor brain tissues (NBT). Moreover, the increase in TMEM2 expression level was closely related to tumor malignancy. The survival analysis showed that TMEM2 high expression reduces survival time in all glioma patients, including GBM and LGG patients. Subsequent experiments demonstrated that knockdown TMEM2 inhibited proliferation of GBM cells. In addition, we analyzed TMEM2 mRNA levels in different GBM subtypes, and demonstrated that TMEM2 expression was upregulated in mesenchymal subtype. Meanwhile, bioinformatics analysis and transwell assay indicated that knockdown TMEM2 suppressed epithelial-mesenchymal transition (EMT) in GBM. Importantly, Kaplan-Meier analysis demonstrated that TMEM2 high expression reduced the treatment response to TMZ in GBM patients. Knockdown of TMEM2 alone did not reduce apoptosis GBM cells, but significant apoptotic cells were observed in the group treated with additional TMZ. These studies may contribute to improving the accuracy of early diagnosis and evaluating the effectiveness of TMZ treatment in GBM patients.

3D slicer combined with neuroendoscope in treatment of a distal segment aneurysm of the anterior choroidal artery complicated intraventricular hemorrhage: A case report and literature review.

Introduction: Pure ventricular hemorrhage is often secondary to Moyamoya disease, rarely caused by rupture of ventricular aneurysm. The surgical treatment of the latter is very challenging. 3D Slicer reconstruction technology can accurately locate small intracranial lesions and combined with minimally invasive surgery with transcranial neuroendoscope is a new attempt to treat the above diseases. Case presentation: We report a case of pure intraventricular hemorrhage secondary to rupture of a distal segment aneurysm of the anterior choroidal artery. Brain computed tomography (CT) before admission showed pure ventricular hemorrhage, and brain CT angiography (CTA) before operation showed a distal segment aneurysm of the anterior choroidal artery. We used 3D Slicer reconstruction and precise location of the focus before the operation and used the minimally invasive surgery technique with transcranial neuroendoscope to completely remove the hematoma in the ventricle, and found the responsible aneurysm located in the ventricle. Conclusion: Pure intraventricular hemorrhage requires vigilance against the distal segment aneurysm of the anterior choroidal artery. At present, conventional microscopic craniotomy and intravascular interventional therapy have limitations, and 3D Slicer reconstruction and precise positioning technology combined with transcranial neuroendoscope minimally invasive surgery may be a good choice.