Myelination- and migration-associated genes are downregulated after phagocytosis in cultured oligodendrocyte precursor cells.

In the central nervous system, microglia are responsible for removing infectious agents, damaged/dead cells, and amyloid plaques by phagocytosis. Other cell types, such as astrocytes, are also recently recognized to show phagocytotic activity under some conditions. Oligodendrocyte precursor cells (OPCs), which belong to the same glial cell family as microglia and astrocytes, may have similar functions. However, it remains largely unknown whether OPCs exhibit phagocytic activity against foreign materials like microglia. To answer this question, we examined the phagocytosis activity of OPCs using primary rat OPC cultures. Since innate phagocytosis activity could trigger cell death pathways, we also investigated whether participating in phagocytosis activity may lead to OPC cell death. Our data shows that cultured OPCs phagocytosed myelin-debris-rich lysates prepared from rat corpus callosum, without progressing to cell death. In contrast to OPCs, mature oligodendrocytes did not show phagocytotic activity against the bait. OPCs also exhibited phagocytosis towards lysates of rat brain cortex and cell membrane debris from cultured astrocytes, but the percentage of OPCs that phagocytosed beta-amyloid was much lower than the myelin debris. We then conducted RNA-seq experiments to examine the transcriptome profile of OPC cultures and found that myelination- and migration-associated genes were downregulated 24 h after phagocytosis. On the other hand, there were a few upregulated genes in OPCs 24 h after phagocytosis. These data confirm that OPCs play a role in debris removal and suggest that OPCs may remain in a quiescent state after phagocytosis.

Renin-angiotensin-aldosterone system inhibitors as a risk factor for chronic subdural hematoma recurrence: A matter of debate.

OBJECTIVES: Chronic subdural hematoma (cSDH) is a common central nervous system condition. Recent reports indicate that cSDH affects long-term prognosis; however, its definitive risk factors remain unknown. An antihypertensive drug, renin-angiotensin-aldosterone system inhibitors (RAASi), can affect vascular permeability and cell proliferation processes, which may suppress the recurrence of cSDH. However, several studies have reported negative results to this effect. Therefore, we aimed to evaluate antihypertensive drugs, including RAASi, as risk factors for recurrent cSDH. MATERIALS AND METHODS: A total of 203 consecutive cases of surgically treated cSDH were retrospectively reviewed. Clinical and radiological parameters were compared between the groups with and without cSDH recurrence to identify risk factors. RESULTS: Of the included cases, 68 (33.5%) used RAASi and 37 (18.2%) developed recurrence within 60 days of surgery. In the multiple logistic regression analysis adjusted by composite risk score, the odds ratios (95% confidence interval) of RAASi, calcium channel blockers, diuretics, ß and α blockers, for the recurrent risk of cSDH after surgery were 2.49 (1.16, 5.42), 1.79 (0.84, 3.82), 1.83 (0.62, 4.87), 0.90 (0.28, 2.44), and 0.96 (0.21, 3.20), respectively. The Cox proportional hazard model also demonstrated that RAASi-use was an independent risk factor for cSDH recurrence. CONCLUSIONS: Present series suggests RAASi-use as a risk factor for cSDH recurrence, although the role of RAASi-use in cSDH remains debatable. Further studies for deeper understanding of the microenvironment of hematoma and the surroundings are preferable. (235 words).

Blood-Brain Barrier Mechanisms in Stroke and Trauma.

The brain microenvironment is tightly regulated. The blood-brain barrier (BBB), which is composed of cerebral endothelial cells, astrocytes, and pericytes, plays an important role in maintaining the brain homeostasis by regulating the transport of both beneficial and detrimental substances between circulating blood and brain parenchyma. After brain injury and disease, BBB tightness becomes dysregulated, thus leading to inflammation and secondary brain damage. In this chapter, we overview the fundamental mechanisms of BBB damage and repair after stroke and traumatic brain injury (TBI). Understanding these mechanisms may lead to therapeutic opportunities for brain injury.

Pineal parenchymal tumor of intermediate differentiation: a systematic review and contemporary management of 389 cases reported during the last two decades.

Pineal parenchymal tumor of intermediate differentiation (PPTID) is a WHO grade II and III tumor arising from pineal parenchymal cells. PPTID is a rare tumor accounting for less than 1% of all primary central nervous system neoplasms. Therefore, reports describing the clinical characteristics and biological features of PPTID are lacking. Moreover, the therapeutic strategy remains controversial. The current study aimed to evaluate treatment results and problems of contemporary therapeutic modalities of PPTID based on its features compared with other pineal parenchymal tumors. A comprehensive systematic literature review of 69 articles was performed, including articles on PPTID (389 patients) and similar tumors. Patient demographics, disease presentation, imaging characteristics, biological features, and current therapeutic options and their results were reviewed. We found that histopathological findings based on current WHO classification are well associated with survival; however, identifying and treating aggressive PPTID cases with uncommon features could be problematic. A molecular and genetic approach may help improve diagnostic accuracy. Therapeutic strategy, especially for grade III and aforementioned uncommon and aggressive tumors, remains controversial. A combination therapy involving maximum tumor resection, chemotherapy, and radiotherapy could be the first line of treatment. However, although challenging, a large prospective study would be required to identify ways to improve the clinical results of PPTID treatment.

Mature Adult Mice With Exercise-Preconditioning Show Better Recovery After Intracerebral Hemorrhage.

Background and Purpose: Physical exercise offers therapeutic potentials for several central nervous system disorders, including stroke and cardiovascular diseases. However, it is still mostly unknown whether and how exercise preconditioning affects the prognosis of intracerebral hemorrhage (ICH). In this study, we examined the effects of preconditioning on ICH pathology in mature adult mice using treadmill exercise. Methods: Male C57BL/6J (25-week old) mice were subjected to 6 weeks of treadmill exercise followed by ICH induction. Outcome measurements included various neurological function tests at multiple time points and the assessment of lesion volume at 8 days after ICH induction. In addition, plasma soluble factors and phagocytotic microglial numbers in the peri-lesion area were also measured to determine the mechanisms underlying the effects of exercise preconditioning. Results: The 6-week treadmill exercise preconditioning promoted recovery from ICH-induced neurological deficits in mice. In addition, mice with exercise preconditioning showed smaller lesion volumes and increased numbers of phagocytotic microglia. Furthermore, the levels of several soluble factors, including endostatin, IGFBP (insulin-like growth factor-binding protein)-2 and -3, MMP (matrix metallopeptidase)-9, osteopontin, and pentraxin-3, were increased in the plasma samples from ICH mice with exercise preconditioning compared with ICH mice without exercise. Conclusions: These results suggest that mice with exercise preconditioning may suffer less severe injury from hemorrhagic stroke, and therefore, a habit of physical exercise may improve brain health even in middle adulthood.

Microglial responses after phagocytosis: Escherichia coli bioparticles, but not cell debris or amyloid beta, induce matrix metalloproteinase-9 secretion in cultured rat primary microglial cells.

Upon infection or brain damage, microglia are activated to play roles in immune responses, including phagocytosis and soluble factor release. However, little is known whether the event of phagocytosis could be a trigger for releasing soluble factors from microglia. In this study, we tested if microglia secrete a neurovascular mediator matrix metalloproteinase-9 (MMP-9) after phagocytosis in vitro. Primary microglial cultures were prepared from neonatal rat brains. Cultured microglia phagocytosed Escherichia coli bioparticles within 2 hr after incubation and started to secrete MMP-9 at around 12 hr after the phagocytosis. A TLR4 inhibitor TAK242 suppressed the E. coli-bioparticle-induced MMP-9 secretion. However, TAK242 did not change the engulfment of E. coli bioparticles in microglial cultures. Because lipopolysaccharides (LPS), the major component of the outer membrane of E. coli, also induced MMP-9 secretion in a dose-response manner and because the response was inhibited by TAK242 treatment, we assumed that the LPS-TLR4 pathway, which was activated by adhering to the substance, but not through the engulfing process of phagocytosis, would play a role in releasing MMP-9 from microglia after E. coli bioparticle treatment. To support the finding that the engulfing step would not be a critical trigger for MMP-9 secretion after the event of phagocytosis in microglia, we confirmed that cell debris and amyloid beta were both captured into microglia via phagocytosis, but neither of them induced MMP-9 secretion from microglia. Taken together, these data demonstrate that microglial response in MMP-9 secretion after phagocytosis differs depending on the types of particles/substances that microglia encountered.

AKAP12 Supports Blood-Brain Barrier Integrity against Ischemic Stroke.

A-kinase anchor protein 12 (AKAP12) is a scaffolding protein that associates with intracellular molecules to regulate multiple signal transductions. Although the roles of AKAP12 in the central nervous system are still relatively understudied, it was previously shown that AKAP12 regulates blood-retinal barrier formation. In this study, we asked whether AKAP12 also supports the function and integrity of the blood-brain barrier (BBB). In a mouse model of focal ischemia, the expression level of AKAP12 in cerebral endothelial cells was upregulated during the acute phase of stroke. Also, in cultured cerebral endothelial cells, oxygen-glucose deprivation induced the upregulation of AKAP12. When AKAP12 expression was suppressed by an siRNA approach in cultured endothelial cells, endothelial permeability was increased along with the dysregulation of ZO-1/Claudin 5 expression. In addition, the loss of AKAP12 expression caused an upregulation/activation of the Rho kinase pathway, and treatment of Rho kinase inhibitor Y-27632 mitigated the increase of endothelial permeability in AKAP12-deficient endothelial cell cultures. These in vitro findings were confirmed by our in vivo experiments using Akap12 knockout mice. Compared to wild-type mice, Akap12 knockout mice showed a larger extent of BBB damage after stroke. However, the inhibition of rho kinase by Y-27632 tightened the BBB in Akap12 knockout mice. These data may suggest that endogenous AKAP12 works to alleviate the damage and dysfunction of the BBB caused by ischemic stress. Therefore, the AKAP12-rho-kinase signaling pathway represents a novel therapeutic target for stroke.

Endothelial Progenitor Cell Secretome and Oligovascular Repair in a Mouse Model of Prolonged Cerebral Hypoperfusion.

BACKGROUND AND PURPOSE: Endothelial progenitor cells (EPCs) have been extensively investigated as a therapeutic approach for repairing the vascular system in cerebrovascular diseases. Beyond vascular regeneration per se, EPCs may also release factors that affect the entire neurovascular unit. Here, we aim to study the effects of the EPC secretome on oligovascular remodeling in a mouse model of white matter injury after prolonged cerebral hypoperfusion. METHODS: The secretome of mouse EPCs was analyzed with a proteome array. In vitro, the effects of the EPC secretome and its factor angiogenin were assessed on primary oligodendrocyte precursor cells and mature human cerebral microvascular endothelial cells (hCMED/D3). In vivo, mice were subjected to permanent bilateral common carotid artery stenosis, then treated with EPC secretome at 24 hours and at 1 week, and cognitive outcome was evaluated with the Y maze test together with oligodendrocyte precursor cell proliferation/differentiation and vascular density in white matter at 4 weeks. RESULTS: Multiple growth factors, cytokines, and proteases were identified in the EPC secretome, including angiogenin. In vitro, the EPC secretome significantly enhanced endothelial and oligodendrocyte precursor cell proliferation and potentiated oligodendrocyte precursor cell maturation. Angiogenin was proved to be a key factor since pharmacological blockade of angiogenin signaling negated the positive effects of the EPC secretome. In vivo, treatment with the EPC secretome increased vascular density, myelin, and mature oligodendrocytes in white matter and rescued cognitive function in the mouse hypoperfusion model. CONCLUSIONS: Factors secreted by EPCs may ameliorate white matter damage in the brain by boosting oligovascular remodeling.

Three-dimensional multimodality fusion imaging as an educational and planning tool for deep-seated meningiomas.

INTRODUCTION: The utility of surgical simulation with three-dimensional multimodality fusion imaging (3D-MFI) has been demonstrated. However, its potential in deep-seated brain lesions remains unknown. The aim of this study was to investigate the impact of 3D-MFI in deep-seated meningioma operations. MATERIAL AND METHODS: Fourteen patients with deeply located meningiomas were included in this study. We constructed 3D-MFIs by fusing high-resolution magnetic resonance (MR) and computed tomography (CT) images with a rotational digital subtraction angiogram (DSA) in all patients. The surgical procedure was simulated by 3D-MFI prior to operation. To assess the impact on neurosurgical education, the objective values of surgical simulation by 3D-MFIs/virtual reality (VR) video were evaluated. To validate the quality of 3D-MFIs, intraoperative findings were compared. The identification rate (IR) and positive predictive value (PPV) for the tumor feeding arteries and involved perforating arteries and veins were also assessed for quality assessment of 3D-MFI. RESULTS: After surgical simulation by 3D-MFIs, near-total resection was achieved in 13 of 14 (92.9%) patients without neurological complications. 3D-MFIs significantly contributed to the understanding of surgical anatomy and optimal surgical view (p < .0001) and learning how to preserve critical vessels (p < .0001) and resect tumors safety and extensively (p < .0001) by neurosurgical residents/fellows. The IR of 3D-MFI for tumor-feeding arteries and perforating arteries and veins was 100% and 92.9%, respectively. The PPV of 3D-MFI for tumor-feeding arteries and perforating arteries and veins was 98.8% and 76.5%, respectively. CONCLUSIONS: 3D-MFI contributed to learn skull base meningioma surgery. Also, 3D-MFI provided high quality to identify critical anatomical structures within or adjacent to deep-seated meningiomas. Thus, 3D-MFI is promising educational and surgical planning tool for meningiomas in deep-seated regions.

Characteristics and surgical strategies for posterior clinoid process meningioma: two case reports and review of the literature.

Clinical and radiological features or characteristics of posterior clinoid process (PCP) meningiomas have rarely been described because of their extreme scarcity and terminological confusion. Therefore, the strategies in the surgical intervention for PCP meningiomas have not been well established. Moreover, the presence of deep and critical neuroanatomical structures and relatively high morbidity, which can be difficult to predict preoperatively, make their surgical excision more challenging. We report two surgical cases of PCP meningioma and discuss the appropriate assessment of preoperative features and surgical strategies with review of the literature. Our study suggests that PCP meningioma may be characterized by the anterior displacement of internal carotid artery, and infero-laterally shifted posterior communicating arteries, and homonymous hemianopsia, a distinctive clinical feature. One of the key issues in PCP meningioma surgery is preservation of the optic nerve. Unlocking the optic nerve by anterior clinoidectomy and dissection, the falciform ligament is the important step to preserve vision for larger tumors. Complication with the perforators is also hazardous of these challenging surgeries than anterior clinoid meningiomas for their specific neuroanatomical structures and might not be feasible to avoid even with additional techniques and critical monitoring. A combination and multi-staged-surgical approach can be options of tailor-made surgical strategy in cases with tumor adhesion to the perforators.

[Efficacy of Recombinant Activated Factor VII for Intractable Bleeding after Cardiovascular Surgery].

UNLABELLED: Recombinant activated factor VII (rFVIIa) has been used for the treatment of hemophilia, factor VII deficiency, and Glanzmann's thrombasthenia. We retrospectively reviewed the effectiveness of rFVIIa for the treatment of uncontrollable bleeding after cardiovascular surgery. MATERIAL AND METHODS: Eight patients received rFVIIa for the treatment of uncontrollable bleeding after admission to the intensive care unit following cardiovascular surgery between April 2009 and July 2014. RESULTS: Blood loss was significantly decreased in 7 of the 8 cases after the administration of rFVIIa (p<0.05). No adverse thromboembolic events were encountered. The quantity of blood loss and prothrombin time-international normalized ratio(PT-INR), activated partial thromboplastin time(APTT), fibrin degradation products(FDP) and D-dimer levels decreased significantly after the administration of rFVIIa (p<0.05). The blood coagulation test values were almost within the normal range at 24 hours after administration. CONCLUSION: In appropriately selected patients, rFVIIa is an effective agent for the treatment of excessive bleeding after cardiovascular surgery.

Occipitocervical fusion with relief of odontoid invagination: atlantoaxial distraction method using cylindrical titanium cage for basilar invagination--case report.

A 65-year-old woman presented with basilar invagination manifesting as neck pain, dysesthesia around the lips, and truncal ataxia. The radiological findings demonstrated invagination of the odontoid process into the medulla oblongata and vertical atlantoaxial subluxation with C1 assimilation. The clivo-axial angle was 88° and the cervicomedullary angle was 115°, indicating severe basilar invagination. We planned occipitocervical fusion with atlantoaxial distraction using a cylindrical titanium cage. C2 pedicle screws were inserted, and the atlantoaxial joint was opened to translocate the odontoid process downward. A cylindrical titanium cage packed with local bone graft was inserted into the opened facet joint space. Occipital-C2 fusion was completed by fastening the occipital bone plates with pedicle screws using titanium rods. Postoperatively, the apex of the odontoid process descended by 7 mm, and the clivo-axial and cervicomedullary angles opened to 112° and 125°, respectively. Invagination of the odontoid process into the medulla oblongata was relieved. The preoperative symptoms improved, and she remained symptom-free without requiring anterior decompression over 2 years. Bone fusion of the atlantoaxial joints was completed with sustained facet distraction 12 months after the surgery, and adequate relief of the basilar invagination was maintained. The atlantoaxial distraction method using a cylindrical titanium cage can be a useful option in posterior fusion surgery for basilar invagination.

Network Meta-Analysis of C5 Palsy After Anterior Cervical Decompression of Three to Six Levels: Comparing Three Different Procedures.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Using a network meta-analysis (NMA), this study aimed to compare the risks of C5 palsy after three different procedures of anterior cervical decompression. SUMMARY OF BACKGROUND DATA: C5 palsy is a well-known complication affecting the quality of life after anterior procedures. Due to the limited evidence on the various procedures available, we evaluate the basis for selection to prevent palsy and achieve maximal decompression in cases spanning 3-6 levels. MATERIALS AND METHODS: We conducted a comprehensive search for C5 palsy and complications after 3representative procedures, including anterior cervical discectomy and fusion (ACDF), anterior cervical corpectomy and fusion (ACCF), and their combination (hybrid), involving 3 to 6 intervertebral levels. The incidence of C5 palsy was compared using a NMA. RESULTS: We identified 1655 patients in 11 studies who met inclusion criteria. Sixty-nine patients (4.2%) developed delayed C5 palsies. The incidences among ACDF, ACCF, and hybrid cases were 2.3% (16/684, 95% CI: 1.4% to 3.8%), 6.4% (39/613, 95% CI: 4.7% to 8.6%), and 3.9% (14/358, 95% CI: 2.3% to 6.5%), respectively ( P < 0.01). A NMA was performed for 15 pairwise comparisons across the 3 procedure arms: ACDF versus hybrid, 7/232 (3.0%) versus 11/234 (4.7%); hybrid versus ACCF, 14/301 (4.3%) versus 18/224 (8.0%); ACCF versus ACDF, 38/523 (7.8%) versus 16/619 (2.6%). Compared with ACDF, the risk of C5 palsy was significantly higher in ACCF (odds ratio: 2.72, 95% CI: 1.47 to 5.01), whereas ACDF versus hybrid did not significantly differ in risk (odds ratio: 1.56, 95% CI: 0.68 to 3.60). CONCLUSION: We determined that ACCF was associated with a higher risk of postoperative C5 palsy than ACDF in cases spanning 3 to 6 intervertebral levels. If practicable, ACDF surgery may be an appropriate choice for cases requiring anterior decompression of 3 to 6 levels. LEVEL OF EVIDENCE: Level III.

Transcriptomic Profiling Reveals Neuroinflammation in the Corpus Callosum of a Transgenic Mouse Model of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is a widespread neurodegenerative disorder characterized by progressive cognitive decline, affecting a significant portion of the aging population. While the cerebral cortex and hippocampus have been the primary focus of AD research, accumulating evidence suggests that white matter lesions in the brain, particularly in the corpus callosum, play an important role in the pathogenesis of the disease. OBJECTIVE: This study aims to investigate the gene expression changes in the corpus callosum of 5xFAD transgenic mice, a widely used AD mouse model. METHODS: We conducted behavioral tests for spatial learning and memory in 5xFAD transgenic mice and performed RNA sequencing analyses on the corpus callosum to examine transcriptomic changes. RESULTS: Our results show cognitive decline and demyelination in the corpus callosum of 5xFAD transgenic mice. Transcriptomic analysis reveals a predominance of upregulated genes in AD mice, particularly those associated with immune cells, including microglia. Conversely, downregulation of genes related to chaperone function and clock genes such as Per1, Per2, and Cry1 is also observed. CONCLUSIONS: This study suggests that activation of neuroinflammation, disruption of chaperone function, and circadian dysfunction are involved in the pathogenesis of white matter lesions in AD. The findings provide insights into potential therapeutic targets and highlight the importance of addressing white matter pathology and circadian dysfunction in AD treatment strategies.

Influence on the accuracy in ChatGPT: Differences in the amount of information per medical field.

OBJECTIVES: Although ChatGPT was not developed for medical use, there is growing interest in its use in medical fields. Understanding its capabilities and precautions for its use in the medical field is an urgent matter. We hypothesized that differences in the amounts of information published in different medical fields would be proportionate to the amounts of training ChatGPT receives in those fields, and hence its accuracy in providing answers. STUDY DESIGN: A non-clinical experimental study. METHODS: We administered the Japanese National Medical Examination to GPT-3.5 and GPT-4 to examine the rates of accuracy and consistency in their responses. We counted the total number of documents in the Web of Science Core Collection per medical field and assessed the relationship with ChatGPT's accuracy. We also performed multivariate-adjusted models to investigate the risk factors for incorrect answers. RESULTS: For GPT-4, we confirmed an accuracy rate of 81.0 % and a consistency rate of 88.8 % on the exam; both showed improvement compared to those for GPT-3.5. A positive correlation was observed between the accuracy rate and consistency rate (R = 0.51, P < 0.001). The number of documents per medical field was significantly correlated with the accuracy rate in that medical field (R = 0.44, P < 0.05), with relatively few publications being an independent risk factor for incorrect answers. CONCLUSIONS: Checking consistency may help identify incorrect answers when using ChatGPT. Users should be aware that the accuracy of the answers by ChatGPT may decrease when it is asked about topics with limited published information, such as new drugs and diseases.

Differential reductions in the capillary red-blood-cell flux between retina and brain under chronic global hypoperfusion.

Significance: It has been hypothesized that abnormal microcirculation in the retina might predict the risk of ischemic damages in the brain. Direct comparison between the retinal and the cerebral microcirculation using similar animal preparation and under similar experimental conditions would help test this hypothesis. Aim: We investigated capillary red-blood-cell (RBC) flux changes under controlled conditions and bilateral-carotid-artery-stenosis (BCAS)-induced hypoperfusion, and then compared them with our previous measurements performed in the brain. Approach: We measured capillary RBC flux in mouse retina with two-photon microscopy using a fluorescence-labeled RBC-passage approach. Key physiological parameters were monitored during experiments to ensure stable physiology. Results: We found that under the controlled conditions, capillary RBC flux in the retina was much higher than in the brain (i.e., cerebral cortical gray matter and subcortical white matter), and that BCAS induced a much larger decrease in capillary RBC flux in the retina than in the brain. Conclusions: We demonstrated a two-photon microscopy-based technique to efficiently measure capillary RBC flux in the retina. Since cerebral subcortical white matter often exhibits early pathological developments due to global hypoperfusion, our results suggest that retinal microcirculation may be utilized as an early marker of brain diseases involving global hypoperfusion.

[Invalid sensors judged by the BIS A-2000 monitors may display clinically acceptable BIS values on the external equipments].

The bispectral index (BIS) is widely used to measure anesthetic levels in the perioperative period. In our hospital, the BIS monitors (A-2000) are connected to bedside monitors and display BIS values on them through outside input. All datas on the bedside monitors are transmitted to anesthesia information management system automatically. We report cases that were impossible to measure BIS values with the displays of "Invalid Sensor" on the BIS A-2000 sensor, but BIS values were measurable on the bedside monitors. One possible reason is thought that the BIS Quatro Sensor transmits both EEG signals and sensor information to the BIS A-2000 monitor separately. BIS A-2000 monitors may process EEG signals and sensor information individually, and transfer BIS parameters to the external equipments, regardless of sensor information.

Bone Invasive Meningioma: Recent Advances and Therapeutic Perspectives.

Meningioma is the most common primary neoplasm of the central nervous system (CNS). Generally, these tumors are benign and have a good prognosis. However, treatment can be challenging in cases with aggressive variants and poor prognoses. Among various prognostic factors that have been clinically investigated, bone invasion remains controversial owing to a limited number of assessments. Recent study reported that bone invasion was not associated with WHO grades, progression, or recurrence. Whereas, patients with longer-recurrence tended to have a higher incidence of bone invasion. Furthermore, bone invasion may be a primary preoperative predictor of the extent of surgical resection. Increasing such evidence highlights the potential of translational studies to understand bone invasion as a prognostic factor of meningiomas. Therefore, this mini-review summarizes recent advances in pathophysiology and diagnostic modalities and discusses future research directions and therapeutic strategies for meningiomas with bone invasion.

Antiplatelet therapy for standalone coiling of ruptured intracranial aneurysms: a systematic review and meta-analysis.

BACKGROUND: Endovascular embolization using standalone coils is the preferred treatment option for ruptured cerebral aneurysms to avoid the use of dual antiplatelet therapy with stent coiling or endoluminal flow diversion devices. However, it has been reported that patients undergoing the standalone coiling approach are at risk for periprocedural thromboembolism. Therefore, this systematic review and meta-analysis was performed to clarify the risks and benefits of antiplatelet therapy (AT) during coiling procedures performed to treat ruptured aneurysms, including the incidence of early thromboembolic events, hemorrhagic and delayed ischemic events, as well as clinical outcomes. METHODS: A comprehensive search of three databases was performed for articles from inception to June 2021. After fulfilling the inclusion criteria, five studies were included in this meta-analysis and 462 patients with aneurysmal subarachnoid hemorrhage (aSAH) were identified who underwent endovascular standalone coiling treatment. Aneurysm location, patient characteristics, and aSAH grades were comparable between the AT and non-AT groups. RESULTS: AT significantly decreased the incidence of thromboembolic events immediately after the coiling procedures compared with non-AT (OR 3.42; 95% CI 1.77 to 6.61, p<0.001). The incidences of hemorrhage, delayed ischemia, and clinical outcomes with or without AT were not significantly different between groups. CONCLUSIONS: Although this study showed no beneficial effect of AT on clinical outcomes, the results suggest that AT could be combined with standalone coiling to avoid thromboembolism during the perioperative period. A large prospective study and/or an additional meta-analysis would be required to further investigate how AT benefits standalone coil embolization in aSAH.

Effects of cerebral amyloid angiopathy on the brain vasculome.

ß-amyloid (Aß) deposits in brain blood vessel walls underlie the vascular pathology of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). Growing evidence has suggested the involvement of cerebrovascular dysfunction in the initiation and progression of cognitive impairment in AD and CAA patients. Therefore, in this study, we assessed the brain vasculome in a mouse model in order to identify cerebrovascular pathways that may be involved in AD and CAA vascular pathogenesis in the context of aging. Brain endothelial cells were isolated from young and old wild-type mice, and young and old transgenic mice expressing Swedish mutation in amyloid precursor protein and exon 9 deletion in presenilin 1 (APPswe/PSEN1dE9). Microarray profiling of these endothelial transcriptomes demonstrated that accumulation of vascular Aß in the aging APPswe/PSEN1dE9 mouse is associated with impaired endothelial expression of neurotransmitter receptors and calcium signaling transductors, while the genes involved in cell cycle and inflammation were upregulated. These results suggest that the vascular pathology of AD and CAA may involve the disruption of neurovascular coupling, reactivation of cell cycle in quiescent endothelial cells, and enhanced inflammation. Further dissection of these endothelial mechanisms may offer opportunities to pursue therapies to ameliorate vascular dysfunction in the aging brain of AD and CAA patients.