Inferior temporal quadrantanopia associated with pituitary adenomas and a potential mechanism of excessive optic nerve bending.

Background: Pituitary adenomas show typical visual field defects that begin superiorly and progress inferiorly. The cause of atypical visual field defects that start inferiorly remains unclear. This study aimed to understand this phenomenon using magnetic resonance imaging (MRI). Methods: A total of 220 patients with pituitary adenomas underwent a visual field assessment of both eyes. Preoperative visual fields were assessed and classified into two types: superior quadrantanopia (typical) and inferior quadrantanopia (atypical). Several parameters related to tumor characteristics and optic nerve compression were evaluated using MRI. Results: Of the 440 eyes examined, 174 (39.5%) had visual field defects. Of these, 28 (16.1%) had typical and 11 (6.3%) had atypical visual field defects. Patient age, tumor size, degree of cavernous sinus invasion, tumor pathology, and intratumor bleeding were similar between the two groups. The angle formed by the optic nerve in the optic canal and in the intracranial subarachnoid space at the exit of the optic canal (degree of optic nerve bending) was significantly larger in the atypical group than in the typical group (42.6° vs. 23.9°, P = 0.046). Conclusion: In some pituitary adenomas, visual field defects begin inferiorly. This may be caused by optic nerve compression on the superior surface by the bony margin of the optic canal exit. Therefore, pituitary adenomas should be considered in patients with atypical visual field defects.

An Efficient Method for Isolating and Purifying Nuclei from Mice Brain for Single-Molecule Imaging Using High-Speed Atomic Force Microscopy.

Nuclear pore complexes (NPCs) on the nuclear membrane surface have a crucial function in controlling the movement of small molecules and macromolecules between the cell nucleus and cytoplasm through their intricate core channel resembling a spiderweb with several layers. Currently, there are few methods available to accurately measure the dynamics of nuclear pores on the nuclear membranes at the nanoscale. The limitation of traditional optical imaging is due to diffraction, which prevents achieving the required resolution for observing a diverse array of organelles and proteins within cells. Super-resolution techniques have effectively addressed this constraint by enabling the observation of subcellular components on the nanoscale. Nevertheless, it is crucial to acknowledge that these methods often need the use of fixed samples. This also raises the question of how closely a static image represents the real intracellular dynamic system. High-speed atomic force microscopy (HS-AFM) is a unique technique used in the field of dynamic structural biology, enabling the study of individual molecules in motion close to their native states. Establishing a reliable and repeatable technique for imaging mammalian tissue at the nanoscale using HS-AFM remains challenging due to inadequate sample preparation. This study presents the rapid strainer microfiltration (RSM) protocol for directly preparing high-quality nuclei from the mouse brain. Subsequently, we promptly utilize HS-AFM real-time imaging and cinematography approaches to record the spatiotemporal of nuclear pore nano-dynamics from the mouse brain.

Astrocyte-induced mGluR1 activates human lung cancer brain metastasis via glutamate-dependent stabilization of EGFR.

There are limited methods to stably analyze the interactions between cancer cells and glial cells in vitro, which hinders our molecular understanding. Here, we develop a simple and stable culture method of mouse glial cells, termed mixed-glial culture on/in soft substrate (MGS), which serves well as a platform to study cancer-glia interactions. Using this method, we find that human lung cancer cells become overly dependent on metabotropic glutamate receptor 1 (mGluR1) signaling in the brain microenvironment. Mechanistically, interactions with astrocytes induce mGluR1 in cancer cells through the Wnt-5a/prickle planar cell polarity protein 1 (PRICKLE1)/RE1 silencing transcription factor (REST) axis. Induced mGluR1 directly interacts with and stabilizes the epidermal growth factor receptor (EGFR) in a glutamate-dependent manner, and these cells then become responsive to mGluR1 inhibition. Our results highlight increased dependence on mGluR1 signaling as an adaptive strategy and vulnerability of human lung cancer brain metastasis.

Determination of Significant Three-Dimensional Hemodynamic Features for Postembolization Recanalization in Cerebral Aneurysms Through Explainable Artificial Intelligence.

BACKGROUND: Recanalization poses challenges after coil embolization in cerebral aneurysms. Establishing predictive models for postembolization recanalization is important for clinical decision making. However, conventional statistical and machine learning (ML) models may overlook critical parameters during the initial selection process. METHODS: In this study, we automated the identification of significant hemodynamic parameters using a PointNet-based deep neural network (DNN), leveraging their three-dimensional spatial features. Further feature analysis was conducted using saliency mapping, an explainable artificial intelligence (XAI) technique. The study encompassed the analysis of velocity, pressure, and wall shear stress in both precoiling and postcoiling models derived from computational fluid dynamics simulations for 58 aneurysms. RESULTS: Velocity was identified as the most pivotal parameter, supported by the lowest P value from statistical analysis and the highest area under the receiver operating characteristic curves/precision-recall curves values from the DNN model. Moreover, visual XAI analysis showed that robust injection flow zones, with notable impingement points in precoiling models, as well as pronounced interplay between flow dynamics and the coiling plane, were important three-dimensional features in identifying the recanalized aneurysms. CONCLUSIONS: The combination of DNN and XAI was found to be an accurate and explainable approach not only at predicting postembolization recanalization but also at discovering unknown features in the future.

Recurrence of an extracranial internal carotid artery aneurysm treated with STA-MCA bypass and trapping due to neovascularization from an ascending pharyngeal artery: illustrative case.

BACKGROUND: Extracranial internal carotid artery aneurysms (EICAs) are rare. Although a high mortality risk has been reported in nonoperated cases, the optimal treatment for EICAs remains unknown. OBSERVATIONS: A 79-year-old female presented with painless swelling in the right neck. Imaging revealed a giant EICA with a maximum diameter of 3.2 cm. Superficial temporal artery-middle cerebral artery bypass and internal carotid artery (ICA) trapping were performed. Because the distal aneurysm edge was at the C1 level, the distal portion of the aneurysm was occluded by endovascular coiling, and the proximal portion was surgically ligated. Blood flow into the aneurysm disappeared after the operation. Three years postsurgery, enlargement of the aneurysm with blood flow from the ascending pharyngeal artery (APA) was detected. The EICA was resected after coiling the APA and ligating both ends of the aneurysm. Pathologically, neovascularization within the aneurysm wall was observed. LESSONS: Even if blood flow into an EICA disappears after ICA trapping, the EICAs can enlarge due to neovascularization from the neighboring artery. From the outset, removal of the aneurysm should be considered as a radical treatment strategy for giant EICAs.

Fluid dynamic analysis in predicting the recanalization of intracranial aneurysms after coil embolization - A study of spatiotemporal characteristics.

Purpose: Hemodynamics play a key role in the management of cerebral aneurysm recanalization after coil embolization; however, the most reliable hemodynamic parameter remains unknown. Previous studies have explored the use of both spatiotemporally averaged and maximal definitions for hemodynamic parameters, based on computational fluid dynamics (CFD) analysis, to build predictive models for aneurysmal recanalization. In this study, we aimed to assess the influence of different spatiotemporal characteristics of hemodynamic parameters on predictive performance. Methods: Hemodynamics were simulated using CFD for 66 cerebral aneurysms from 65 patients. We evaluated 14 types of spatiotemporal definitions for two hemodynamic parameters in the pre-coiling model and five in virtual post-coiling model (VM) created by cutting the aneurysm from the pre-coiling model. A total of 91 spatiotemporal hemodynamic features were derived and utilized to develop univariate predictor (UP) and multivariate logistic regression (LR) models. The model's performance was assessed using two metrics: the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). Results: Different spatiotemporal hemodynamic features exhibited a wide range of AUROC values ranging from 0.224 to 0.747, with 22 feature pairs showing a significant difference in AUROC value (P-value <0.05), despite being derived from the same hemodynamic parameter. PDave,q1 was identified as the strongest UP with AUROC/AUPRC values of 0.747/0.385, yielding sensitivity and specificity value of 0.889 and 0.614 at the optimal cut-off value, respectively. The LR model further improved the prediction performance, having AUROC/AUPRC values of 0.890/0.903. At the optimal cut-off value, the LR model achieved a specificity of 0.877, sensitivity of 0.719, outperforming the UP model. Conclusion: Our research indicated that the characteristics of hemodynamic parameters in terms of space and time had a significant impact on the development of predictive model. Our findings suggest that LR model based on spatiotemporal hemodynamic features could be clinically useful in predicting recanalization after coil embolization in patients, without the need for invasive procedures.

Safety and efficacy of the endoscopic transsphenoidal transclival approach performed using direct cortical stimulation for pontine cavernous malformations.

OBJECTIVE: Surgical treatment of brainstem cavernous malformations (CMs) is challenging. Surgery using the endoscopic transsphenoidal transclival approach (eTSTCA) is reported as a useful alternative for ventral brainstem CMs. However, CMs located in the ventral midline of the brainstem are rare, and only a small number of case reports on these CMs treated with the eTSTCA exist. The efficacy and safety of the eTSTCA have not yet been fully examined. METHODS: A retrospective analysis was performed for 5 consecutive patients who underwent surgery via the eTSTCA for treating ventral pontine CMs. RESULTS: The average maximum CM diameter was 26.0 mm (18-38 mm). All patients underwent MR-diffusion tensor imaging, which confirmed that the corticospinal tract (CST) deviated posteriorly or laterally to the CM. Direct brainstem cortical stimulation was performed to localize the CST before making the cortical incision. After the excision of the CM, the cavity was filled with artificial CSF to make an aqueous surgical field (wet-field technique) for observing the tumor cavity and confirming complete hemostasis and resection. Total removal was achieved in all patients. The preoperative modified Rankin Scale score was 3 in 3 patients and 4 in 2 patients, whereas it was 1 in 2 patients and 0 in 3 patients 3 months after surgery. Postoperative CSF leakage was observed in 1 patient, and transient abducens nerve palsy was observed in 1 patient. No other intra- or postoperative complications were observed. CONCLUSIONS: MR-diffusion tensor imaging and direct brainstem cortical stimulation were useful to ascertain the proximity of the CST to the CM. The endoscope provides a clear view even underwater, and it was safe and effective to observe the entire CM cavity and confirm complete hemostasis without additional retraction of the brainstem parenchyma, including the CST. The eTSTCA provides a direct access point to the lesion and may be a safer alternative treatment for patients whose CST deviates laterally or posteriorly to the CM.

Distinct subdivisions of subcortical U-fiber regions in the gyrencephalic ferret brain.

The human cerebrum contains a large amount of cortico-cortical association fibers. Among them, U-fibers are short-range association fibers located in white matter immediately deep to gray matter. Although U-fibers are thought to be crucial for higher cognitive functions, the organization within U-fiber regions are still unclear. Here we investigated the properties of U-fiber regions in the ferret cerebrum using neurochemical, neuronal tracing, immunohistochemical and electron microscopic techniques. We found that U-fiber regions can be subdivided into two regions, which we named outer and inner U-fiber regions. We further uncovered that outer U-fiber regions have smaller-diameter axons with thinner myelin compared with inner U-fiber regions. These findings may indicate functional complexity within U-fiber regions in the cerebrum.

Periprocedural antiplatelet medication assessed by VerifyNow for neuroendovascular treatment: Comparison of prasugrel with clopidogrel.

OBJECTIVE: The maintenance dose of prasugrel (PRAS) for neuroendovascular treatment requires much research. We report the antiplatelet effect of PRAS measured by VerifyNow P2Y12 reaction units (PRUs) in patients during the perioperative period of neuroendovascular treatment. METHODS: Between January 2017 and January 2023, 230 patients who underwent endovascular treatment for unruptured intracranial aneurysms or carotid artery stenosis at our institution were retrospectively identified. Patients received dual antiplatelet therapy with 100 mg aspirin (ASA) and 75 mg clopidogrel (CLP)/day (CLP group, n = 186) or 100 mg ASA and 3.75 mg PRAS/day (PRAS group, n = 44) 2 weeks before the procedures. The PRU value was compared between the CLP and PRAS groups. In the study, we defined 95≦PRU < 208 as the optimal range. Perioperative complications within seven days of surgery were also analyzed. RESULTS: The mean value of PRU was significantly low in the PRAS group (179.13 ± 66.03 in CLP vs. 154.75 ± 54.01 in PRAS, p = 0.024). The proportion of the patients who exhibited 95≦PRU < 208 was significantly higher in the PRAS group (55.4% vs. 72.7%, p = 0.036). Ischemic and hemorrhagic complication rates were not significantly different between the CLP and PRAS groups (7.6% vs. 0%, p = 0.076; 4.7% vs. 0%, p = 0.361). The ischemic complication rate was higher in patients with a PRU > 208 than in those with PRU < 208 (12.5% vs. 3.8%, p = 0.044). The hemorrhagic complication rate was not significantly different between the PRU < 95 and 95≦PRU groups (8.4% vs. 3.2%, p = 0.224). CONCLUSIONS: Maintenance dose PRAS further decreased the PRU value and reached the optimal range in more cases than CLP during the perioperative period of neuroendovascular treatment. Ischemic complications significantly increased in the 208 < PRU group.

Mentalizing can be Impaired in Patients with Meningiomas Originating in the Anterior Skull Base.

OBJECTIVE: Mentalizing is an essential function of our social lives. Impairment of mentalizing due to meningiomas has not received attention because most patients return to their social lives after surgical treatment. We investigated the influence of meningiomas and their surgical resection on mentalizing. METHODS: Low- and high-level mentalizing were retrospectively examined in 61 patients with meningiomas and 14 healthy volunteers. Mentalizing was assessed using the facial expression recognition test and picture arrangement test of the Wechsler Adult Intelligence Scale, third edition, before and after surgery. We examined the influence of tumor localization on mentalizing and recovery from mentalizing disorders after tumor resection. Voxel-based lesion-symptom mapping was performed to investigate the relationship between impairments in mentalizing and tumor location. RESULTS: Before surgery, mentalizing was impaired significantly in patients with meningiomas compared to those in the control group (low-level: P = 0.015, high-level: P = 0.011). This impairment was associated with contact between the tumor and frontal lobe (low-level: P = 0.036, high-level: P = 0.047) and was severe in patients with tumors arising in the anterior skull base (low-level: P = 0.0045, high-level: P = 0.043). Voxel-based lesion-symptom mapping revealed that when the basal cortex of the frontal lobe was compressed by the tumor, the risk of impaired mentalizing was high. The region responsible for high-level mentalizing was located deeper than that responsible for low-level mentalizing. After the surgical removal of the tumor, the test scores significantly improved (low-level: P = 0.035, high-level: P = 0.045). CONCLUSIONS: Mentalizing was impaired by meningiomas arising from the anterior skull base, but it can improve after surgical resection of the tumors.

Retrospective Observational Study of Patients With Subdural Hematoma Treated With Idarucizumab.

Use of anticoagulants is increasing with the aging of societies. The safe first-line drug is likely to be a direct oral anticoagulant (DOAC), but outcomes of treatment of traumatic brain injury (TBI) with anticoagulants are uncertain. Therefore, we examined the clinical effect of idarucizumab as reversal therapy in elderly patients with TBI who were treated with dabigatran. A retrospective multi-center observational study was performed in patients ≥65 years of age who developed acute traumatic subdural hematoma during treatment with dabigatran and underwent reversal therapy with idarucizumab. The items examined included patient background, neurological and imaging findings at arrival, course after admission, complications, and outcomes. A total of 23 patients were enrolled in the study. The patients had a mean age of 78.9 years. Cause of TBI was fall in 60.9% of the subjects. Mean Glasgow Coma Scale score at arrival was 8.7; anisocoria was present in 31.8% of cases. Exacerbation of consciousness was found in 30.4%, but only in 13.3% of subjects treated with idarucizumab before consciousness and imaging findings worsened. Dabigatran was discontinued in 81.8% of cases after hematoma development, with a mean withdrawal period of 12.1 days. The favorable outcome rate was 21.7%, and mortality was 39.1%. In multi-variate analysis, timing of idarucizumab administration was associated with a favorable outcome. There were ischemic complications in 3 cases (13.1%), and all three events occurred ≥7 days after administration of idarucizumab. These findings suggest that in cases that develop hematoma during treatment with dabigatran, it is important to administer idarucizumab early and restart dabigatran after conditions stabilize.

Glioblastomas at the white matter of temporo-parietal junction cause a poor postoperative independence level.

INTRODUCTION: Right cerebral hemispheric glioblastomas (GBMs) often decrease the Karnofsky performance status (KPS) score postoperatively, despite the patient having sufficient patient function while performing daily living. This study aimed to evaluate the factors that could cause poor KPS scores during the postoperative chronic phase in patients with right cerebral hemispheric GBMs. METHODS: Data of 47 patients with newly diagnosed right cerebral hemispheric GBMs were analyzed. All patients were assessed preoperatively and 3 months postoperatively to determine KPS and brain function. To determine tumor location related to the postoperative KPS scores, we used voxel-based lesion symptom mapping (VLSM). The patients were divided into two groups (involvement and non-involvement groups) based on whether their lesion involved a significant region identified by VLSM. We then compared functional factors and prognosis between the groups using the chi-squared and log-rank tests, respectively. RESULTS: The KPS score significantly decreased after surgery compared to that preoperatively measured (p = 0.023). VLSM revealed that tumors in the white matter of temporo-parietal junction (WM-TPJ) caused a significant decline in the KPS score at three months postoperatively. The patients in the involvement group had a higher probability of impaired attention, visuospatial cognition, emotion recognition, and visual field than did those in the non-involvement group. In addition, tumor in the WM-TPJ were associated with shorter progression-free survival and overall survival (p = 0.039 and 0.023, respectively). CONCLUSIONS: GBMs involving the right WM-TPJ are more likely to result in poor postoperative KPS scores and prognoses. Impairments of several kinds of brain functions caused by tumor invasion to the WM-TPJ may be associated with lower KPS scores.

Epidemiological and therapeutic profiles of lung cancer patients in the Hokushin Region Japan: a retrospective hospital administrative database study.

OBJECTIVE: This study was performed to validate the epidemiology, initial treatment, and clinical practice of lung cancer patients in the Hokushin region, Japan. METHODS: We retrospectively surveyed data of 5503 newly diagnosed and registered lung cancer patients in 22 principal hospital-based cancer registries in Hokushin region linked with health insurance claims data for registered patients between 2016 and 2017. RESULTS: The patients consisted of 3677 (66.8%) men and 1826 (33.2%) women with a mean (range) age of 72.2 (27-103) years). Diagnoses were small cell lung cancer (n = 512, 9.4%), squamous cell carcinoma (n = 1083, 19.7%), and non-squamous non-small cell lung cancer (NSCLC; n = 3906, 70.9%). The population with stage I disease in Toyama prefecture (41.1%) was smaller than in the other three prefectures associated with reduced selection of initial surgical therapy and increased frequencies of stage IV disease (33.2%) and best supportive care (18.6%). Initial chemotherapy for stage IV non-squamous NSCLC consisted of tyrosine kinase inhibitors in 39.3% of cases for EGFR and 4% of cases for ALK-positive non-squamous NSCLC, followed by platinum compounds (25.9%) non-platinum compounds (12.9%), and immune checkpoint inhibitors (10.2%). Carboplatin was the commonly prescribed first-line cytotoxic chemotherapeutic agent (65.4% of patients under 75 years and in 96.7% of patients over 75 years). CONCLUSION: This study revealed real-world data on epidemiological and treatment status in lung cancer in four prefectures in Hokushin region, Japan. Simultaneous analysis of nationwide registry and insurance data could provide valuable insights for the development of lung cancer screening and medical treatment strategies. In addition, the comparative data analysis with other lesions or countries will be useful for evaluating the differences in clinical practice of cancer managements.

Nuclear transport surveillance of p53 by nuclear pores in glioblastoma.

Nuclear pore complexes (NPCs) are the central apparatus of nucleocytoplasmic transport. Disease-specific alterations of NPCs contribute to the pathogenesis of many cancers; however, the roles of NPCs in glioblastoma (GBM) are unknown. In this study, we report genomic amplification of NUP107, a component of NPCs, in GBM and show that NUP107 is overexpressed simultaneously with MDM2, a critical E3 ligase that mediates p53 degradation. Depletion of NUP107 inhibits the growth of GBM cell lines through p53 protein stabilization. Mechanistically, NPCs establish a p53 degradation platform via an export pathway coupled with 26S proteasome tethering. NUP107 is the keystone for NPC assembly; the loss of NUP107 affects the integrity of the NPC structure, and thus the proportion of 26S proteasome in the vicinity of nuclear pores significantly decreases. Together, our findings establish roles of NPCs in transport surveillance and provide insights into p53 inactivation in GBM.

Association Between Risperidone Use and Kidney Function Decline in Patients with Schizophrenia: A Retrospective Cohort Study.

PURPOSE: Several D-amino acids have been shown to be protective against kidney injury in mice. Risperidone, a currently used atypical antipsychotic agent for schizophrenia, is also known to inhibit the activity of D-amino acid oxidase, which degrades certain D-amino acids. Based on the hypothesis that risperidone would prevent kidney disease progression, this study investigated the association between risperidone use and kidney function decline in patients with schizophrenia. METHODS: This retrospective cohort study included patients who were diagnosed with schizophrenia and had data available from two or more serum creatinine measurements between April 1, 2010, and March 31, 2020. Patients who used risperidone for at least 30 days were included in the risperidone group, whereas those who had no record of risperidone use were included in the control group. Cox regression models were used to evaluate the risk for 40% decline in estimated glomerular filtration rate (eGFR) in patients treated with risperidone compared to that in the control group. FINDINGS: Overall, 212 patients used risperidone and 1468 patients had no record of risperidone use. The mean age was 55 years, 759 (45%) of the patients were male, and the mean eGFR at baseline was 88 mL/min/1.73 m2. The mean age in the risperidone group was less than that in the control group (52 vs 56 years); other baseline characteristics were comparable between the two groups. During a mean follow-up of 1.6 years, 267 patients (16%) had a 40% eGFR decline. The incidence rate of 40% eGFR decline was lower in the risperidone group than in the control group (60 vs 104 per 1000 person-years). After adjustment for baseline age, sex, and eGFR, risperidone use was associated with a decreased risk for 40% eGFR decline (hazard ratio = 0.54; 95% CI, 0.33-0.87; P = 0.01). IMPLICATIONS: Risperidone use may be associated with decreased risk for kidney function decline in patients with schizophrenia. Further studies are warranted to validate these findings.

α-SMA positive vascular mural cells suppress cyst formation in hemangioblastoma.

Approximately 60% of hemangioblastomas (HBs) have peritumoral cysts adjacent to the tumor, which can cause neurological deficits due to the mass effect, and the management of cyst formation is a clinical challenge. Vascular mural cells surrounding endothelial cells consist of vascular smooth muscle cells (vSMCs) and pericytes, which are essential elements that support blood vessels and regulate permeability. This study investigated the involvement of mural cells in cyst formation. We analyzed the expression of α-smooth muscle actin (α-SMA), platelet-derived growth factor receptor-beta (PDGFRB), and CD31 in 39 consecutive human cerebellar HBs, 20 of cystic and 19 of solid type. Solid type HBs showed stronger diffuse expression of α-SMA in precapillary arterioles and capillaries within the tumor than cystic type HBs (p = 0.001), whereas there was no difference in PDGFRB and CD31 expression. Detailed observation with immunofluorescence demonstrated that α-SMA was expressed in vascular mural cells surrounding capillaries in the solid rather than in the cystic type. Multivariate analysis including various clinical and pathological factors showed that lower α-SMA expression was significantly correlated with cyst formation (p < 0.001). Our data suggested that vascular mural cells from precapillary arterioles to capillaries expressing α-SMA may be pericytes and play a crucial role in HB cystogenesis.

Sympathetic Nervous Hyperactivity Impairs Microcirculation Leading to Early Brain Injury After Subarachnoid Hemorrhage.

BACKGROUND: Although early brain injury (EBI) is recognized as a critical step following subarachnoid hemorrhage (SAH), its pathophysiology and underlying mechanisms remain poorly understood. Herein, we investigated the role of cerebral circulation in the acute phase using patient data and a mouse SAH model and evaluated its regulation via the sympathetic nervous system. METHODS: The cerebral circulation time and neurological outcomes in the human body were retrospectively examined in 34 SAH cases with ruptured anterior circulation aneurysms and 85 cases with unruptured anterior circulation cerebral aneurysms at Kanazawa University Hospital from January 2016 to December 2021. In a mouse study, a SAH model was created via endovascular perforation, and India-ink angiography was performed over time. Additionally, bilateral superior cervical ganglionectomy was performed immediately before surgery, and neurological scores and brain water content were evaluated after SAH. RESULTS: Cerebral circulation time was prolonged in the acute phase of SAH compared with that in the unruptured cerebral aneurysm group, especially in those with electrocardiographic changes. Furthermore, it was more prolonged in the poor prognosis group (modified Rankin Scale scores 3-6) than in the good prognosis group (modified Rankin Scale scores 0-2) at discharge. In mice, cerebral perfusion was significantly reduced at 1 and 3 hours after SAH and recovered at 6 hours. superior cervical ganglionectomy improved cerebral perfusion without altering the diameter of the middle cerebral artery at 1 hour and improved neurological outcomes at 48 hours after SAH. Consistently, brain edema, quantified by brain water content, was improved by superior cervical ganglionectomy 24 hours after SAH. CONCLUSIONS: Sympathetic hyperactivity may play a critical role in the development of EBI by impairing cerebral microcirculation and edema in the acute phase following SAH.

Therapeutic potential of pentamidine for glioma-initiating cells and glioma cells through multimodal antitumor effects.

Glioma-initiating cells, which comprise a heterogeneous population of glioblastomas, contribute to resistance against aggressive chemoradiotherapy. Using drug reposition, we investigated a therapeutic drug for glioma-initiating cells. Drug screening was undertaken to select candidate agents that inhibit proliferation of two different glioma-initiating cells lines. The alteration of proliferation and stemness of the two glioma-initiating cell lines, and proliferation, migration, cell cycle, and survival of these two differentiated glioma-initiating cell lines and three different glioblastoma cell lines treated with the candidate agent were evaluated. We also used a xenograft glioma mouse model to evaluate anticancer effects of treated glioma cell lines. Among the 1301 agents, pentamidine-an antibiotic for Pneumocystis jirovecii-emerged as a successful antiglioma agent. Pentamidine treatment suppressed proliferation and stemness in glioma-initiating cell lines. Proliferation and migration were inhibited in all differentiated glioma-initiating cells and glioblastoma cell lines, with cell cycle arrest and caspase-dependent apoptosis induction. The in vivo study reproduced the same findings as the in vitro studies. Pentamidine showed a stronger antiproliferative effect on glioma-initiating cells than on differentiated cells. Western blot analysis revealed pentamidine inhibited phosphorylation of signal transducer and activator of transcription 3 in all cell lines, whereas Akt expression was suppressed in glioma-initiating cells but not in differentiated lines. In the present study, we identified pentamidine as a potential therapeutic drug for glioma. Pentamidine could be promising for the treatment of glioblastomas by targeting both glioma-initiating cells and differentiated cells through its multifaceted antiglioma effects.

Intra-Brain and Plasma Levels of L-Serine Are Associated with Cognitive Status in Patients with Chronic Kidney Disease.

Introduction: The number of patients with chronic kidney disease (CKD) is increasing worldwide. Cognitive impairment is one of the comorbidities of CKD. With the increased number of aged population, novel biomarkers of impaired cognitive function are required. Intra-body profile of amino acid (AA) is reportedly altered in patients with CKD. Although some AAs act as neurotransmitters in the brain, it is not clear whether altered AA profile are associated with cognitive function in patients with CKD. Therefore, intra-brain and plasma levels of AAs are evaluated with respect to cognitive function in patients with CKD. Methods: Plasma levels of AAs were compared between 14 patients with CKD, including 8 patients with diabetic kidney disease, and 12 healthy controls to identify the alteration of specific AAs in CKD. Then, these AAs were evaluated in the brains of 42 patients with brain tumor using non-tumor lesion of the resected brain. Cognitive function is analyzed with respect to intra-brain levels of AAs and kidney function. Moreover, plasma AAs were analyzed in 32 hemodialyzed patients with/without dementia. Results: In patients with CKD, plasma levels of asparagine (Asn), serine (Ser), alanine (Ala), and proline (Pro) were increased as compared to patients without CKD. Among these AAs, L-Ser, L-Ala, and D-Ser show higher levels than the other AAs in the brain. Intra-brain levels of L-Ser was correlated with cognitive function and kidney function. The number of D-amino acid oxidase or serine racemase-positive cells was not correlated with kidney function. Moreover, the plasma levels of L-Ser are also decreased in patients with declined cognitive function who are treated with chronic hemodialysis. Conclusion: The decreased levels of L-Ser are associated with impaired cognitive function in CKD patients. Especially, plasma L-Ser levels may have a potential for novel biomarker of impaired cognitive function in patients with hemodialysis.

Optical coherence tomography detects early optic nerve damage before visual field defect in patients with pituitary tumors.

Optical coherence tomography (OCT) is a useful tool for predicting visual recovery after the removal of pituitary tumors. However, the utility of OCT in patients with pituitary tumors and a normal visual field is unclear. We aimed to analyze OCT features in pituitary tumors without visual field defects. Pituitary tumors without visual field defects were selected. A total of 138 eyes from 69 patients, assessed by the Humphrey visual field test and OCT, were enrolled in this study. Using preoperative coronal sections of MR images, patients were divided into chiasmal compression (CC) and non-chiasmal compression (non-CC) groups, and OCT characteristics were examined. The CC and non-CC groups consisted of 40 and 29 patients, respectively. There were no differences in age, sex, tumor type, or degree of visual field testing, but the tumor size was different between the two groups. On OCT, macular thickness ganglion cell complex (mGCC) was significantly thinner in the CC group than that in the non-CC group (112.5 vs 117.4 um, P < 0.05). Based on a database of healthy participants, 24% and 2% of eyes in the CC and non-CC groups had abnormal mGCC thickness (P < 0.01), respectively. In a sub-analysis of the CC group, patients with an abnormal mGCC thickness were older than a normal one (58.2 vs 41.1 years, p < 0.01). OCT can detect early optic nerve damage due to optic CC by pituitary tumors, even in normal visual fields. The degree of mGCC thinning may provide an appropriate surgical timing for pituitary tumors that compress the optic chiasm.