Cancer stem‐like cells, which have been described as tumor‐initiating cells or tumor‐propagating cells, play a crucial role in our fundamental understanding of glioblastoma multiforme (GBM) and its recurrence. GBM is a lethal cancer, characterized by florid vascularization and aberrantly elevated vascular endothelial growth factor (VEGF). VEGF promotes tumorigenesis and angiogenesis of human GBM stem‐like cells (GBSCs). However, whether and how VEGF contributes to GBSCs proliferation remain largely uncertain. In this study, human GBSCs were isolated from surgical specimens of glioblastoma and cultured in medium favored for stem cell growth. Neural Colony‐Forming Cell Assay and ATP assay were performed to measure GBSC proliferation under normoxia (20% O₂) and hypoxia (1% O₂). Our observations demonstrate that exogenous VEGF stimulates GBSC proliferation in a dose‐dependent manner via VEGF Receptor 2 (VEGFR2); while VEGF Receptor 1 (VEGFR1) has a negative feedback effect on VEGFR2 when cells were exposed to higher concentration of VEGF. These results suggest that suppressing VEGFR2‐dependent GBSC proliferation is a potentially therapeutic strategy in GBM.

Melatonin, a well-known antioxidant, has been shown to possess anti-invasive properties for glioma. However, little is known about the effect of melatonin on glioma cell migration and invasion under hypoxia, which is a crucial microenvironment for tumor progress. In addition, focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2) are closely associated with cell migration and invasion. Therefore, we investigated the possible role of these kinases and its related signaling in the regulation of human U251 glioma cells behavior by melatonin under hypoxia. The abilities of migration and invasion of U251 glioma cells were determined by wound healing and transwell assay in vitro. The intracellular production of reactive oxygen species (ROS) was measured by using the fluorescent probe 6-carboxy-2′, 7′-dichorodihydrofluorescein diacetate (DCFH-DA). Immunofluorescence experiments and western blotting analysis were used to detect the expression level of protein. Small interfering RNAs (siRNA) was used to silence specific gene expression. The pharmacologic concentration (1 mM) of melatonin significantly inhibited the migration and invasion of human U251 glioma cells under hypoxia. The inhibitory effect of melatonin was accompanied with the reduced phosphorylation of FAK and Pyk2, and decreased expression of alpha v beta 3 (αvβ3) integrin. Additionally, inhibition of αvβ3 integrin by siRNA reduced the phosphorylation of FAK/Pyk2 and demonstrated the similar anti-tumor effects as melatonin, suggesting the involvement of αvβ3 integrin- FAK/Pyk2 pathway in the anti-migratory and anti-invasive effect of melatonin. It was also found that melatonin treatment decreased the ROS levels in U251 glioma cells cultured under hypoxia. ROS inhibitor apocynin not only inhibited αvβ3 integrin expression and the phosphorylation levels of FAK and Pyk2, but also suppressed the migratory and invasive capacity of U251 glioma cells under hypoxia. These results suggest that melatonin exerts anti-migratory and anti-invasive effects on glioma cells in response to hypoxia via ROS-αvβ3 integrin-FAK/Pyk2 signaling pathways. This provides evidence that melatonin may be a potential therapeutic molecule targeting the hypoxic microenvironment of glioma.

Background: Sex differences in the outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) remain controversial. The aim of this study was to evaluate sex differences in the outcomes of patients with aSAH.Method: This study retrospectively analyzed the clinical data of consecutive patients with aSAH, admitted to the Department of Neurosurgery, Wuhan University Zhongnan Hospital, from May 1, 2020 to December 31, 2020. The modified Rankin Scale (mRS) score was used to evaluate the prognosis of patients at discharge. Outcome indicators included cerebral ischemia, hydrocephalus, and mRS ≥ 2 at discharge.Results: The majority (65%) of the 287 patients with aSAH included in the study were females. Patients were divided into female (n = 184) and male (n = 99) groups; the female patients were significantly older than the male patients (61.3 ± 8.5 years vs. 60.0 ± 8.5 years, p = 0.032). The incidence of comorbidities (hypertension, diabetes, and heart disease) was higher in the female group than in the male group, but the difference was not statistically significant. Although more female patients than male patients underwent endovascular treatment, there was no statistical difference in the treatment approach between the two groups. Comparison of post-operative complications and mRS scores at discharge revealed that the rate of cerebral ischemia and mRS ≥ 2 at discharge were significantly higher among female patients than among male patients. Moreover, this difference persisted after propensity adjustment for age and treatment approach. Analysis of risk factors for poor prognosis at discharge in both pre- and post-adjustment patients revealed cerebral ischemia and high mFisher score (mFisher = 3/4) to be independent risk factors.Conclusion: Female patients with aSAH have a worse prognosis than male patients, and this difference may be because women are more susceptible to cerebral ischemia.

Anti-angiogenic therapy inhibits tumor growth and is considered as a potential clinical therapy for malignant glioma. However, inevitable recurrences and unexpected tumor resistance, particularly increased invasion ability of glioma cell, were observed after anti-angiogenic treatment. The underlying mechanism remains undetermined. Focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2) are closely associated with cell migration; therefore, we investigated the possible role of these kinases in rat C6 glioma cell invasion induced by bevacizumab, a recombinant monoclonal antibody against vascular endothelial growth factor (VEGF).

Meningioangiomatosis (MA) is a rare hamartomatous or meningovascular lesion involving the central nervous system, and is sometimes associated with intracranial meningiomas. Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare, slow-growing benign tumor-like lesions that can occur anywhere along the neuraxis. Here, we report a rare case of MA combined with CAPNON. A 31-year-old woman was admitted to our hospital because of a high-density mass in the left frontal lobe, detected by computed tomography (CT) during a physical examination. She had a 3-year history of obsessive–compulsive disorder. We describe the imaging, histopathological, and molecular characteristics of the patient. To our knowledge, this is the first report describing MA combined with CAPNON. We reviewed the literature on MA and CAPNON over the last decade and summarized the points for differential diagnosis and treatment. It is difficult to preoperatively distinguish between MA and CAPNON. However, this coexisting condition should be considered when intra-axial calcification lesions are observed on radiological imaging. Accurate diagnosis and appropriate treatment are likely to benefit this patient group.

Background: Capillary hemangiomas of the central nervous system are exceedingly rare. Previously documented cases have predominantly been located in the intracranial or spinal regions, with the majority presenting as solitary focal lesions. Case description: A 57-year-old woman complained back pain, urinary problems, and numbness and weakness in the lower extremities. MRI revealed thickening and enhancement of the entire spinal dura mater, anomalous enhancement signals surrounding cerebral blood vessels, and DSA revealed multiple malformed vascular clusters in the intracranial and spinal cord regions. Subsequently, a dural biopsy confirmed the pathological diagnosis of capillary hemangioma, with further whole-genome sequencing to identify potential gene mutations. Conclusions: Central nervous system capillary hemangiomas can affect the entire spinal cord and intracranial meningeal tissues simultaneously. Genetic alterations, including PDE4DIP mutations, were identified, but their clinical significance remains unclear.