Displacement of Gray Matter and Incidence of Seizures in Patients with Cerebral Cavernous Malformations

Seizures are the most common presentation in patients with cerebral cavernous malformations (CCMs). Based on the hypothesis that the volume or proportion of gray matter (GM) displaced by CCMs is associated with the risk of seizure, we developed an algorithm by which to quantify the volume and proportion of displaced GM and the risk of seizure. Image analysis was conducted on 111 patients with solitary CCMs (divided into seizure and nonseizure groups) from our gamma knife radiosurgery (GKRS) database from February 2005 and March 2020. The CCM algorithm proved effective in quantifying the GM and CCM using T1WI MRI images. In the seizure group, 11 of the 12 patients exhibited seizures at the initial presentation, and all CCMs in the seizure group were supratentorial. The location of the limbic lobe within the CCM was significantly associated with the risk of seizure (OR = 19.6, p = 0.02). The risk of seizure increased when the proportion of GM displaced by the CCM exceeded 31%. It was also strongly correlated with the volume of displaced GM. The volume and proportion of displaced GM were both positively correlated with the risk of seizure presentation/development and thus could be used to guide seizure prophylaxis in CCM patients

The presence of TP53 and dedifferentiation of low-grade glioma: A rare possible adverse effect of radiotherapy?

SummaryRadiotherapy and radiosurgery are important modes of treatment for benign and malignant brain tumors. Radiation-induced tumors and radiation-induced malignant transformation of tumors have been described in many reports. Radiotherapy is one of the standard treatments for intracranial glial tumors. However, there is limited discussion of radiation carcinogenesis in glioma treatment. We present a 58-year-old male who was initially diagnosed to have low-grade glioma in an eloquent area of the brain by stereotactic biopsy. The tumor progressed rapidly after radiotherapy and a second stereotactic biopsy was done. Based on the WHO classification, the diagnosis for the second specimen was high-grade glioma. Histopathology showed that the expression of TP53 had increased from 40% to 60% in the second specimen. The finding was consistent with other reports of the malignant transformation of benign tumor after radiotherapy. Radiation carcinogenesis may be one of the causes for tumor progression to high-grade within 6 months. The effect of radiotherapy on the control of glioma is well-documented. Radiation carcinogenesis, which could cause malignant transformation of benign brain tumors, could also be observed in low-grade glioma. This report clearly indicates that caution is warranted regarding the use of radiotherapy for glial tumors, especially for low-grade gliomas

Intermittent Hypoxia Inhibits Na+-H+ Exchange-Mediated Acid Extrusion Via Intracellular Na+ Accumulation in Cardiomyocytes

Background/Aims: Intermittent hypoxia (IH) has been shown to exert preconditioning-like cardioprotective effects. It also has been reported that IH preserves intracellular pH (pHi) during ischemia and protects cardiomyocytes against ischemic reperfusion injury. However, the exact mechanism is still unclear. Methods: In this study, we used proton indicator BCECF-AM to analyze the rate of pHi recovery from acidosis in the IH model of rat neonatal cardiomyocytes. Neonatal cardiomyocytes were first treated with repetitive hypoxia-normoxia cycles for 1-4 days. Cells were then acid loaded with NH4Cl, and the rate of pHi recovery from acidosis was measured. Results: We found that the pHi recovery rate from acidosis was much slower in the IH group than in the room air (RA) group. When we treated cardiomyocytes with Na+-H+ exchange (NHE) inhibitors (Amiloride and HOE642) or Na+-free Tyrode solution during the recovery, there was no difference between RA and IH groups. We also found intracellular Na+ concentration ([Na+]i) significantly increased after IH exposure for 4 days. However, the phenomenon could be abolished by pretreatment with ROS inhibitors (SOD and phenanathroline), intracellular calcium chelator or Na+-Ca2+ exchange (NCX) inhibitor. Furthermore, the pHi recovery rate from acidosis became faster in the IH group than in the RA group when inhibition of NCX activity. Conclusions: These results suggest that IH would induce the elevation of ROS production. ROS then activates Ca2+-efflux mode of NCX and results in intracellular Na+ accumulation. The rise of [Na+]i further inhibits the activity of NHE-mediated acid extrusion and retards the rate of pHi recovery from acidosis during IH

The Regulating Effect of CII-3 and Its Active Components from Periplaneta americana on M1/M2 Macrophage Polarization

CII-3 is the effective part of Periplaneta americana for application in oncotherapy. This study investigated its main chemical components for macrophage polarization regulation activity. Compounds were separated and purified, and their structures were elucidated based on NMR and HR-ESI-MS analyses. After inducing the M1 and M2 phenotype macrophages, CII-3 and testing components were added and co-incubated to evaluate their effects on the relevant markers of macrophages. Then, gradient concentrations of CII-3 and active monomers were further investigated for their effects on M2 macrophages. The effects were detected by RT-PCR, ELISA, flow cytometry, and immunofluorescence. Twelve compounds were identified from CII-3. CII-3 and pericanaside (5) had no obvious effect on M1 macrophages, while they significantly reduced the expression levels of M2 macrophage markers. Specifically, they significantly reduced the levels of TGF-β and IL-10 and the mRNA expression levels of ARG-1 and CD206 in the M2 phenotypes of RAW264.7 and Ana-1 macrophages. The conditioned medium of CII-3 and pericanaside (5) could inhibit the migration capacity of CT26.WT tumor cells. Macrophage M1/M2 polarization is a dynamic equilibrium, and the M2 phenotype, which can promote the growth of tumor cells, is relatively highly expressed in the tumor microenvironment. CII-3 and pericanaside could significantly reduce the phenotype of M2-type macrophages, indicating that the anti-tumor activity of CII-3 could be related to the inhibitory effect on M2 polarization, and pericanaside was one of the active components

Bilobulated paraclinoid aneurysm mimics double aneurysms: A comparison of endovascular coiling and surgical clipping treatments

AbstractThis report presents two cases of subarachnoid hemorrhage caused by rupture of paraclinoid aneurysms. Both aneurysms presented a bilobulated appearance upon image study. Both cases were treated successfully, the first with surgical clipping and the second with endovascular coiling. The special bilobulated feature of paraclinoid aneurysm in this particular anatomic location suggests its close relationship with the carotid dural ring. This relationship caused varying degrees of difficulty in both coiling and clipping the aneurysm. We compared the limitations and advantages of both treatments, and suggest that surgical clipping may be the treatment of choice in this region

Enhancement of Radiosurgical Treatment Outcome Prediction Using MRI Radiomics in Patients with Non-Small Cell Lung Cancer Brain Metastases

The diagnosis of brain metastasis (BM) is commonly observed in non-small cell lung cancer (NSCLC) with poor outcomes. Accordingly, developing an approach to early predict BM response to Gamma Knife radiosurgery (GKRS) may benefit the patient treatment and monitoring. A total of 237 NSCLC patients with BMs (for survival prediction) and 256 patients with 976 BMs (for prediction of local tumor control) treated with GKRS were retrospectively analyzed. All the survival data were recorded without censoring, and the status of local tumor control was determined by comparing the last MRI follow-up in patients’ lives with the pre-GKRS MRI. Overall 1763 radiomic features were extracted from pre-radiosurgical magnetic resonance images. Three prediction models were constructed, using (1) clinical data, (2) radiomic features, and (3) clinical and radiomic features. Support vector machines with a 30% hold-out validation approach were constructed. For treatment outcome predictions, the models derived from both the clinical and radiomics data achieved the best results. For local tumor control, the combined model achieved an area under the curve (AUC) of 0.95, an accuracy of 90%, a sensitivity of 91%, and a specificity of 89%. For patient survival, the combined model achieved an AUC of 0.81, an accuracy of 77%, a sensitivity of 78%, and a specificity of 80%. The pre-radiosurgical radiomics data enhanced the performance of local tumor control and survival prediction models in NSCLC patients with BMs treated with GRKS. An outcome prediction model based on radiomics combined with clinical features may guide therapy in these patients

Intermittent Hypoxia Prevents Myocardial Mitochondrial Ca2+ Overload and Cell Death during Ischemia/Reperfusion: The Role of Reactive Oxygen Species

It has been documented that reactive oxygen species (ROS) contribute to oxidative stress, leading to diseases such as ischemic heart disease. Recently, increasing evidence has indicated that short-term intermittent hypoxia (IH), similar to ischemia preconditioning, could yield cardioprotection. However, the underlying mechanism for the IH-induced cardioprotective effect remains unclear. The aim of this study was to determine whether IH exposure can enhance antioxidant capacity, which contributes to cardioprotection against oxidative stress and ischemia/reperfusion (I/R) injury in cardiomyocytes. Primary rat neonatal cardiomyocytes were cultured in IH condition with an oscillating O2 concentration between 20% and 5% every 30 min. An MTT assay was conducted to examine the cell viability. Annexin V-FITC and SYTOX green fluorescent intensity and caspase 3 activity were detected to analyze the cell death. Fluorescent images for DCFDA, Fura-2, Rhod-2, and TMRM were acquired to analyze the ROS, cytosol Ca2+, mitochondrial Ca2+, and mitochondrial membrane potential, respectively. RT-PCR, immunocytofluorescence staining, and antioxidant activity assay were conducted to detect the expression of antioxidant enzymes. Our results show that IH induced slight increases of O2−· and protected cardiomyocytes against H2O2- and I/R-induced cell death. Moreover, H2O2-induced Ca2+ imbalance and mitochondrial membrane depolarization were attenuated by IH, which also reduced the I/R-induced Ca2+ overload. Furthermore, treatment with IH increased the expression of Cu/Zn SOD and Mn SOD, the total antioxidant capacity, and the activity of catalase. Blockade of the IH-increased ROS production abolished the protective effects of IH on the Ca2+ homeostasis and antioxidant defense capacity. Taken together, our findings suggest that IH protected the cardiomyocytes against H2O2- and I/R-induced oxidative stress and cell death through maintaining Ca2+ homeostasis as well as the mitochondrial membrane potential, and upregulation of antioxidant enzymes