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Cerebral small vessel disease (CSVD) is a group of pathologies that affect the cerebral blood vessels. CSVD accounts for 25% of strokes and contributes to 45% of dementia. However, the pathogenesis of CSVD remains unclear, involving a variety of complex mechanisms. CSVD may result from dysfunction in the glymphatic system (GS). The GS contains aquaporin-4 (AQP-4), which is in the perivascular space, at the endfeet of the astrocyte. The GS contributes to the removal of waste products from the central nervous system, occupying perivascular spaces and regulating the exchange and movement of cerebrospinal fluid and interstitial fluid. The GS involves astrocytes and aquaporin channels, which are components of the blood-brain barrier, and problems with them may constitute the pathogenesis of CSVD. Vascular risk factors, including diabetes, dilate the perivascular space, disrupting the glymphatic system and the active regulation of AQP-4. CSVD exacerbation due to disorders of the GS is associated with multiple vasculopathies. Dysfunction of the glymphatic system and AQP-4 interferes with the functioning of the blood-brain barrier, which exacerbates CSVD. In a long-term follow-up of CSVD patients with microbleeds, lacunar infarcts, and white matter hyperintensity, several vascular risk factors, including hypertension, increased the risk of ischemic stroke. Dysfunction of the GS may be the cause of CSVD; however, the underlying treatment needs to be studied further.
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Acuaporina 4 , Barrera Hematoencefálica , Enfermedades de los Pequeños Vasos Cerebrales , Sistema Glinfático , Enfermedades de los Pequeños Vasos Cerebrales/metabolismo , Enfermedades de los Pequeños Vasos Cerebrales/patología , Enfermedades de los Pequeños Vasos Cerebrales/etiología , Humanos , Sistema Glinfático/metabolismo , Sistema Glinfático/patología , Acuaporina 4/metabolismo , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , Animales , Astrocitos/metabolismo , Astrocitos/patología , Factores de RiesgoRESUMEN
The physicochemical properties of biomaterials influence cell adhesion, shape, and polarization of macrophages. In this study, we aimed to evaluate the polarization of macrophages in terms of the regulation of cell adhesion and how synthetic mimics for heparin and poly(sodium-4-styrenesulfonate) can regulate macrophage polarization by modulating cell shape, focal adhesion, cell traction force, and intracellular tension. Our initial findings showed that macrophages cultured with heparin-mimicking polymer-based hydrogel matrix showed reduced expression of cell adhesion markers such as integrins, vinculin, RhoA, and ROCK1/2 and reduced cell shape, elongation, cell-matrix traction force, and intracellular tension. Furthermore, we observed a significant decrease in cell adhesion in cells cultured on the hydrogel, resulting in the promotion of M1 polarization. These findings offer insights into the important roles of cell-matrix interactions in macrophage polarization and offer a platform for heparin-mimicking polymer-based hydrogel matrices to induce M1 polarization by inducing cell adhesion without classical activators.
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Hidrogeles , Polímeros , Adhesión Celular , Heparina/farmacología , Heparina/metabolismo , Macrófagos/metabolismo , Polímeros/farmacología , Polímeros/metabolismo , Materiales BiomiméticosRESUMEN
The low-density-lipoprotein receptor (LDLr) removes low-density lipoprotein (LDL), an endovascular transporter that carries cholesterol from the bloodstream to peripheral tissues. The maintenance of cholesterol content in the brain, which is important to protect brain function, is affected by LDLr. LDLr co-localizes with the insulin receptor and complements the internalization of LDL. In LDLr deficiency, LDL blood levels and insulin resistance increase, leading to abnormal cholesterol control and cognitive deficits in atherosclerosis. Defects in brain cholesterol metabolism lead to neuroinflammation and blood-brain-barrier (BBB) degradation. Moreover, interactions between endoplasmic reticulum stress (ER stress) and mitochondria are induced by ox-LDL accumulation, apolipoprotein E (ApoE) regulates the levels of amyloid beta (Aß) in the brain, and hypoxia is induced by apoptosis induced by the LDLr defect. This review summarizes the association between neurodegenerative brain disease and typical cognitive deficits.
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Encefalopatías Metabólicas , Disfunción Cognitiva , Péptidos beta-Amiloides , Animales , Colesterol/metabolismo , Disfunción Cognitiva/etiología , Humanos , Lipoproteínas LDL , Ratones , Ratones Noqueados , Receptores de LDL/metabolismoRESUMEN
Stroke is the leading cause of death and neurological disorders worldwide. However, diagnostic techniques and treatments for stroke patients are still limited for certain types of stroke. Intensive research has been conducted so far to find suitable diagnostic techniques and treatments, but so far there has been no success. In recent years, various studies have drawn much attention to the clinical value of utilizing the mechanism of exosomes, low toxicity, biodegradability, and the ability to cross the blood-brain barrier. Recent studies have been reported on the use of biomarkers and protective and recovery effects of exosomes derived from stem cells or various cells in the diagnostic stage after stroke. This review focuses on publications describing changes in diagnostic biomarkers of exosomes following various strokes and processes for various potential applications as therapeutics.
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Exosomas , Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular , Biomarcadores , Humanos , Células Madre , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapiaRESUMEN
PURPOSE: Few nationally representative studies have evaluated the epidemiology of PA (pituitary adenoma). This South Korean study evaluated the incidence of different PA subtypes, cardiovascular disease (CVD), and related mortality. METHODS: This population-based study evaluated 31,898 patients with PA during 2005-2015. The incidence of PA, mortality, and CVD occurrence in PA cases were evaluated during a median follow-up of 5.3 years (range: 0-10 years). Cox regression analysis was used to evaluate the associations between CVD and mortality. RESULTS: The annual incidences (per 100,000 population) were 3.5 for non-functioning pituitary adenoma (NFPA), 1.6 for prolactinoma (PRL), 0.5 for growth hormone-secreting pituitary adenoma (GH), and 0.2 for adrenocorticotropic or thyroid-stimulating hormone-secreting pituitary adenoma (ACTH + TSH). The standardized mortality ratios were 1.9 for ACTH + TSH, 1.7 for NFPA with hypopituitarism, 1.4 for NFPA without hypopituitarism, 1.3 for GH, and 1.1 for PRL. During 2005-2015, the overall incidence of CVD among PA patients was 6.6% (2106 cases), and the standardized incidence ratios were 4.1 for hemorrhagic stroke, 3.0 for ischemic stroke, and 1.7 for acute myocardial infarction. The standardized incidence ratios for stroke were significantly higher in the ACTH + TSH and NFPA groups, which also had higher risks of CVD-related mortality, relative to the PRL and GH groups. CONCLUSION: South Korea had a relatively high incidence of NFPA. The incidence of stroke was highest for ACTH + TSH and NFPA, which was directly related to mortality during long-term follow-up. Patients with these types of PA should receive stroke prevention measures to reduce their risk of mortality.
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Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Hipopituitarismo/epidemiología , Hipopituitarismo/mortalidad , Neoplasias Hipofisarias/epidemiología , Neoplasias Hipofisarias/mortalidad , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Corea (Geográfico)/epidemiología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Subarachnoid hemorrhage is a potentially devastating cerebrovascular attack with a high proportion of poor outcomes and mortality. Recent studies have reported decreased mortality with the improvement in devices and techniques for treating ruptured aneurysms and neurocritical care. This study investigated the relationship between hospital volume and short- and long-term mortality in patients treated with subarachnoid hemorrhage. METHODS: We selected subarachnoid hemorrhage patients treated with clipping and coiling from March-May 2013 to June-August 2014 using data from Acute Stroke Registry, and the selected subarachnoid hemorrhage (SAH) patients were tracked in connection with data of Health Insurance Review and Assessment Service to evaluate the short-term and long-term mortality. RESULTS: A total of 625 subarachnoid hemorrhage patients were admitted to high-volume hospitals (n = 355, 57%) and low-volume hospitals (n = 270, 43%) for six months. The mortality of SAH patients treated with clipping and coiling was 12.3%, 20.2%, 21.4%, and 24.3% at 14 days, three months, one year, and five years, respectively. The short-term and long-term mortality in high-volume hospitals was significantly lower than that in low-volume hospitals. On Cox regression analysis of death in patients with severe clinical status, low-volume hospitals had significantly higher mortality than high-volume hospitals during short-term follow-up. On Cox regression analysis in the mild clinical status group, there was no statistical difference between high-volume hospitals and low-volume hospitals. CONCLUSION: In subarachnoid hemorrhage patients treated with clipping and coiling, low-volume hospitals had higher short-term mortality than high-volume hospitals. These results from a nationwide database imply that acute SAH should be treated by a skilled neurosurgeon with adequate facilities in a high-volume hospital.
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Complicaciones Posoperatorias/epidemiología , Accidente Cerebrovascular/etiología , Hemorragia Subaracnoidea/mortalidad , Adolescente , Adulto , Anciano , Bases de Datos Factuales , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Sistema de Registros , República de Corea/epidemiología , Accidente Cerebrovascular/epidemiología , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Genetic factors have been known to play a role in the etiology of moyamoya disease (MMD); however, population-level studies quantifying familial risk estimates are unavailable. We aimed to quantify familial incidence and risk for MMD in first-degree relatives (FDR) in the general population of Korea. METHODS: By using the Korean National Health Insurance database which has complete population coverage and confirmed FDR information, we constructed a cohort of 21 940 795 study subjects constituting 12 million families with blood-related FDR and followed them for a familial occurrence of MMD from 2002 to 2017. Incidence risk ratios were calculated as MMD incidence in individuals with affected FDR compared with those without affected FDR, according to age, sex, and family relationships. RESULTS: Among total study subjects, there were 22 459 individuals with affected FDR, of whom 712 familial cases developed MMD with an incidence of 21.8/104 person-years. Overall, the familial risk for MMD was 132-fold higher in individuals with versus without affected FDR. Familial risk (incidence risk ratio; incidence/104 person-years) increased with the degree of genetic relatedness, being highest in individuals with an affected twin (1254.1; 230.0), followed by a sibling (212.4; 35.6), then mother (87.7; 14.4) and father (62.5; 10.4). Remarkably, there was no disease concordance between spouses. The risks were age-dependent and were particularly high in younger age groups. Familial risks were similar in males and females, and the risk of disease transmission was higher in same-sex parent-offspring and sibling pairs. CONCLUSIONS: Our study indicates that genetic predisposition is the predominant driver in MMD pathogenesis, with minimal contribution of environmental factors. These results could be utilized to direct future genetic studies and clinical risk counseling.
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Enfermedad de Moyamoya/epidemiología , Enfermedad de Moyamoya/genética , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Preescolar , Estudios de Cohortes , Bases de Datos Factuales , Padre , Femenino , Predisposición Genética a la Enfermedad , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Madres , República de Corea/epidemiología , Factores de Riesgo , Hermanos , Esposos , Gemelos , Adulto JovenRESUMEN
Glioblastoma (GBM) is the most aggressive and common malignant and CNS tumor, accounting for 47.7% of total cases. Glioblastoma has an incidence rate of 3.21 cases per 100,000 people. The regulation of autophagy, a conserved cellular process involved in the degradation and recycling of cellular components, has been found to play an important role in GBM pathogenesis and response to therapy. Autophagy plays a dual role in promoting tumor survival and apoptosis, and here we discuss the complex interplay between autophagy and GBM. We summarize the mechanisms underlying autophagy dysregulation in GBM, including PI3K/AKT/mTOR signaling, which is most active in brain tumors, and EGFR and mutant EGFRvIII. We also review potential therapeutic strategies that target autophagy for the treatment of GBM, such as autophagy inhibitors used in combination with the standard of care, TMZ. We discuss our current understanding of how autophagy is involved in TMZ resistance and its role in glioblastoma development and survival.
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Autofagia , Resistencia a Antineoplásicos , Glioblastoma , Temozolomida , Humanos , Autofagia/efectos de los fármacos , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Glioblastoma/genética , Glioblastoma/metabolismo , Temozolomida/farmacología , Temozolomida/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Transducción de Señal/efectos de los fármacos , AnimalesRESUMEN
Current chemical treatments for cerebrovascular disease and neurological disorders have limited efficacy in tissue repair and functional restoration. Induced pluripotent stem cells (iPSCs) present a promising avenue in regenerative medicine for addressing neurological conditions. iPSCs, which are capable of reprogramming adult cells to regain pluripotency, offer the potential for patient-specific, personalized therapies. The modulation of molecular mechanisms through specific growth factor inhibition and signaling pathways can direct iPSCs' differentiation into neural stem cells (NSCs). These include employing bone morphogenetic protein-4 (BMP-4), transforming growth factor-beta (TGFß), and Sma-and Mad-related protein (SMAD) signaling. iPSC-derived NSCs can subsequently differentiate into various neuron types, each performing distinct functions. Cell transplantation underscores the potential of iPSC-derived NSCs to treat neurodegenerative diseases such as Parkinson's disease and points to future research directions for optimizing differentiation protocols and enhancing clinical applications.
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Genotype V (GV) Japanese encephalitis virus (JEV) has been predominantly reported in the Republic of Korea (ROK) since 2010. GV JEV exhibits higher virulence and distinct antigenicity compared to other genotypes, which results in reduced efficacy of existing vaccines. Research on GV JEV is essential to minimize its clinical impact, but the only available clinical strain in the ROK is K15P38, isolated from the cerebrospinal fluid of a patient in 2015. We obtained this virus from National Culture Collection for Pathogens (NCCP) and isolated a variant forming small plaques during our research. We identified that this variant has one amino acid substitution each in the PrM and NS5 proteins compared to the reported K15P38. Additionally, we confirmed that this virus exhibits delayed propagation in vitro and an attenuated phenotype in mice. The isolation of this variant is a critical reference for researchers intending to study K15P38 obtained from NCCP, and the mutations in the small plaque-forming virus are expected to be useful for studying the pathology of GV JEV.
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Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Genotipo , Virus de la Encefalitis Japonesa (Especie)/genética , Virus de la Encefalitis Japonesa (Especie)/aislamiento & purificación , Virus de la Encefalitis Japonesa (Especie)/clasificación , Encefalitis Japonesa/virología , Animales , Humanos , Ratones , República de Corea , Virulencia , Ensayo de Placa Viral , Sustitución de Aminoácidos , Femenino , Mutación , Línea Celular , Ratones Endogámicos BALB C , Replicación ViralRESUMEN
Japanese encephalitis (JE), caused by the Japanese encephalitis virus (JEV) infection, continues to pose significant public health challenges worldwide despite efficient vaccines. The virus is classified into five genotypes, among which genotype V (GV) was not detected for a long period after its initial isolation in 1952, until reports emerged from China and the Republic of Korea (ROK) since 2009. The characteristics of the virus are crucial in estimating its potential epidemiological impact. However, characterization of GV JEVs has so far been limited to two strains: Muar, the original isolate, and XZ0934, isolated in China. Two additional ROK GV JEV isolates, NCCP 43279 and NCCP 43413, are currently available, but their characteristics have not been explored. Our phylogenetic analysis revealed that GV virus sequences from the ROK segregate into two clades. NCCP 43279 and NCCP 43413 belong to different clades and exhibit distinct in vitro phenotypes. NCCP 43279 forms larger plaques but demonstrates inefficient propagation in cell culture compared to NCCP 43413. In vivo, NCCP 43279 induces higher morbidity and mortality in mice than NCCP 43413. Notably, NCCP 43279 shows more severe blood-brain barrier damage, suggesting superior brain invasion capabilities. Consistent with its higher virulence, NCCP 43279 displays more pronounced histopathological and immunopathological outcomes. In conclusion, our study confirms that the two ROK isolates are not only classified into different clades but also exhibit distinct in vitro and in vivo characteristics.
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Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Genotipo , Filogenia , Virus de la Encefalitis Japonesa (Especie)/genética , Virus de la Encefalitis Japonesa (Especie)/aislamiento & purificación , Virus de la Encefalitis Japonesa (Especie)/clasificación , Animales , República de Corea/epidemiología , Encefalitis Japonesa/virología , Encefalitis Japonesa/veterinaria , Encefalitis Japonesa/epidemiología , Ratones , Humanos , Virulencia , Línea Celular , FemeninoRESUMEN
Evaluating cell metabolism is crucial during pluripotent stem cell (PSC) differentiation and somatic cell reprogramming as it affects cell fate. As cultured stem cells are heterogeneous, a comparative analysis of relative metabolism using existing metabolic analysis methods is difficult, resulting in inaccuracies. In this study, we measured human PSC basal metabolic levels using a Seahorse analyzer. We used fibroblasts, human induced PSCs, and human embryonic stem cells to monitor changes in basal metabolic levels according to cell number and determine the number of cells suitable for analysis. We evaluated normalization methods using glucose and selected the most suitable for the metabolic analysis of heterogeneous PSCs during the reprogramming stage. The response of fibroblasts to glucose increased with starvation time, with oxygen consumption rate and extracellular acidification rate responding most effectively to glucose 4 hours after starvation and declining after 5 hours of starvation. Fibroblasts and PSCs achieved appropriate responses to glucose without damaging their metabolism 2â¼4 and 2â¼3 hours after starvation, respectively. We developed a novel method for comparing basal metabolic rates of fibroblasts and PSCs, focusing on quantitative analysis of glycolysis and oxidative phosphorylation using glucose without enzyme inhibitors. This protocol enables efficient comparison of energy metabolism among cell types, including undifferentiated PSCs, differentiated cells, and cells undergoing cellular reprogramming, and addresses critical issues, such as differences in basal metabolic levels and sensitivity to normalization, providing valuable insights into cellular energetics.
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Objective: We aimed to examine the effectiveness and safety of a novel torque-controlled catheter for cerebral angiography. Methods: A total of 417 patients who underwent routine transfemoral cerebral angiography were enrolled in a randomized controlled study to compare the new torque-controlled and control group catheters. Device success was assessed on parameters such as the assessment of the common carotid artery, device rotation force, and success rate with the crossover group after the failed procedure. Four neurointerventionalists investigated the degree of satisfaction of using the new device. Superiority and non-inferiority tests of satisfaction scores were estimated for the new torque-controlled and the control group catheters. Results: The new torque-controlled catheter showed improved performance in terms of technical device success (92.79 vs. 98.09 %, P = 0.010), crossover after technical device failure (0 vs. 86.67 %, P = 0.004), and common carotid artery access (92.79 vs. 98.56 %, P = 0.004). The flexibility and rotational force of the new torque-controlled catheter were higher than those of the control group catheters (75.48 vs. 100 %, P < 0.001). No marked adverse cerebrovascular accidents or vessel damage occurred in either group during the procedure. The differences between the two groups in terms of the device rotational force and operator satisfaction were 1.836 (1.765-1.907) and 2.092 (2.000-2.183), respectively. The new torque-controlled catheter showed superior device rotational force satisfaction, operator satisfaction, and manufacturer satisfaction, with statistical significance. Conclusion: The new torque-controlled catheter was effective, safe, and convenient compared to the control group catheters for diagnostic cerebrovascular angiography.
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Objective: Intracerebral hemorrhage (ICH) accompanies higher mortality rates than other type of stroke. This study aimed to investigate the association between hospital volume and mortality for cases of ICH. Methods: We used nationwide data from 2013 to 2018 to compare high-volume hospitals (≥32 admissions/year) and low-volume hospitals (<32 admissions/year). We tracked patients' survival at 3-month, 1-year, 2-year, and 4-year endpoints. The survival of ICH patients was analyzed at 3-month, 1-year, 2-year, and 4-year endpoints using Kaplan-Meier survival analysis. Multivariable logistic regression analysis and Cox regression analysis were performed to determine predictive factors of poor outcomes at discharge and death. Results: Among 9,086 ICH patients who admitted to hospital during 18-month period, 6,756 (74.4%) and 2,330 (25.6%) patients were admitted to high-volume and low-volume hospitals. The mortality of total ICH patients was 18.25%, 23.87%, 27.88%, and 35.74% at the 3-month, 1-year, 2-year, and 4-year, respectively. In multivariate logistic analysis, high-volume hospitals had lower poor functional outcome at discharge than low-volume hospitals (odds ratio, 0.80; 95% confidence interval, 0.72-0.91; p < 0.001). In the Cox analysis, high-volume hospitals had significantly lower 3-month, 1-year, 2-year, and 4-year mortality than low-volume hospitals (p < 0.05). Conclusion: The poor outcome at discharge, short- and long-term mortality in ICH patients differed according to hospital volume. High-volume hospitals showed lower rates of mortality for ICH patients, particularly those with severe clinical status.
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OBJECTIVE: Carotid artery stenting (CAS) is currently widely used for the treatment of carotid artery stenosis. The objective of this study was to analyze the outcomes of CAS performed in a single institution. METHODS: We retrospectively analyzed 313 CAS cases from January 2007 to December 2020, including 206 (66%) symptomatic and 107 (34%) asymptomatic cases. Procedure-related morbidity and mortality were assessed. Rates of periprocedural (≤30 days after CAS) and postprocedural ipsilateral strokes (>30 days after CAS) were also assessed. Logistic regression analysis was used to identify risk factors for the periprocedural complication, in-stent restenosis (ISR), and ipsilateral stroke. RESULTS: The success rate of CAS was 98%. Among 313 cases, 1 patient died due to hyperperfusion-related intracerebral hemorrhage (ICH). The CAS-related mortality rate was 0.31%. The overall incidence of periprocedural complications is 5.1%. A risk factor for periprocedural complication was a symptomatic carotid artery stenosis (7.3% vs. 0.9%, p=0.016). Twenty cases of ISR occurred during 63.7±42.1 months of follow-up. The overall incidence of ISR was 10.2% (20/196). A risk factors for ISR were diabetes mellitus (17.6% vs. 5.7%, p=0.008) and patients who used Open-cell stents (19.6% vs. 6.9%, p=0.010). The overall incidence of ipsilateral stroke is 5.6%. A risk factors for ipsilateral stroke was ISR (95% CI, p=0.002). CONCLUSIONS: CAS is a safe and effective procedure for carotid artery stenosis. Although the incidence of complications is low, fatal complication such as hyperperfusion- related ICH can occur. To prevent hyperperfusion-related ICH, several methods such as strict blood pressure (BP) control, intentional less widening of stenotic segment should be used. To prevent ISR or stroke occurrence, special attention should be paid to patients who have ISR or ipsilateral stroke risk factors.
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Objective: Markers of neuroinflammation during ischemic stroke are well characterized, but additional markers of neural damage are lacking. The study identified associations of behavioral disorders after stroke with histologic neural damage and molecular biological change. Methods: 8-week-old, 25g male mice of the C57BL/6J strain were subjected to middle cerebral artery occlusion (MCAO) to induce ischemic stroke. The control group was a healthy wild type (WT), and the experimental group were designed as a low severity MCAO1 and a high severity MCAO2 based on post-stroke neurological scoring. All groups underwent behavioral tests, real-time polymerase chain reaction (rt-PCR), triphenyltetrazolium chloride (TTC) staining and hematoxylin and eosin (H&E) staining. One-way analysis of variance (ANOVA) was used to analyze statistical significance between groups. Results: In TTC staining, MCAO1 showed 29.02% and MCAO2 showed 38.94% infarct volume (p<0.0001). The pro-inflammatory cytokine interleukin (IL)-1ß was most highly expressed in MCAO2 (WT 0.44 vs MCAO1 2.69 vs MCAO2 5.02, p<0.0001). From the distance to target in the Barnes maze test, WT had a distance of 178 cm, MCAO1 had a distance of 276 cm, and MCAO2 had a distance of 1051 (p=0.0015). The latency to target was 13.3 seconds for WT, 27.9 seconds for MCAO1, and 87.9 seconds for MCAO2 (p=0.0007). Prospero homeobox 1 (Prox1) was most highly expressed in MCAO2 (p=0.0004). Doublecortin (Dcx) was most highly expressed in MCAO2 (p<0.0001). Conclusion: The study demonstrated that histological damage to neural cells and changes in brain mRNA expression were associated with behavioral impairment after ischemic stroke. Prox1 and Dcx may be biomarkers of neural damage associated with long-term cognitive decline, and increased expression at the mRNA level was consistent with neural damage and long-term cognitive dysfunction.
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BACKGROUND: Malignant glioma is among the most lethal and frequently occurring brain tumors, and the average survival period is 15 months. Existing chemotherapy has low tolerance and low blood-brain barrier (BBB) permeability; therefore, the required drug dose cannot be accurately delivered to the tumor site, resulting in an insufficient drug effect. METHODS: Herein, we demonstrate a precision photodynamic tumor therapy using a photosensitizer (ZnPcS) capable of binding to albumin in situ, which can increase the permeability of the BBB and accurately target glioma. Albumin-binding ZnPcS was designed to pass through the BBB and bind to secreted protein acidic and rich in cysteine (SPARC), which is abundant in the glioma plasma membrane. RESULTS: When the upper part of a mouse brain was irradiated using a laser (0.2 W cm- 2) after transplantation of glioma and injection of ZnPcS, tumor growth was inhibited by approximately 83.6%, and the 50% survival rate of the treatment group increased by 14 days compared to the control group. In glioma with knockout SPARC, the amount of ZnPcS entering the glioma was reduced by 63.1%, indicating that it can target glioma through the SPARC pathway. CONCLUSION: This study showed that the use of albumin-binding photosensitizers is promising for the treatment of malignant gliomas.
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OBJECTIVE: We aimed to evaluate the efficacy of EmboTrap II in terms of first-pass recanalization and to determine whether it could yield favorable outcomes. MATERIALS AND METHODS: In this multicenter, prospective study, we consecutively enrolled patients who underwent mechanical thrombectomy using EmboTrap II as a front-line device. The primary outcome was the first pass effect (FPE) rate defined by modified Thrombolysis In Cerebral Infarction (mTICI) grade 2c or 3 by the first pass of EmboTrap II. In addition, modified FPE (mFPE; mTICI grade 2b-3 by the first pass of EmboTrap II), successful recanalization (final mTICI grade 2b-3), and clinical outcomes were assessed. We also analyzed the effect of FPE on a modified Rankin Scale (mRS) score of 0-2 at 3 months. RESULTS: Two hundred-ten patients (mean age ± standard deviation, 73.3 ± 11.4 years; male, 55.7%) were included. Ninety-nine patients (47.1%) had FPE, and mFPE was achieved in 150 (71.4%) patients. Successful recanalization was achieved in 191 (91.0%) patients. Among them, 164 (85.9%) patients underwent successful recanalization by exclusively using EmboTrap II. The time from groin puncture to FPE was 25.0 minutes (interquartile range, 17.0-35.0 minutes). Procedure-related complications were observed in seven (3.3%) patients. Symptomatic intracranial hemorrhage developed in 14 (6.7%) patients. One hundred twenty-three (58.9% of 209 completely followed) patients had an mRS score of 0-2. Sixteen (7.7% of 209) patients died during the follow-up period. Patients who had successful recanalization with FPE were four times more likely to have an mRS score of 0-2 than those who had successful recanalization without FPE (adjusted odds ratio, 4.13; 95% confidence interval, 1.59-10.8; p = 0.004). CONCLUSION: Mechanical thrombectomy using the front-line EmboTrap II is effective and safe. In particular, FPE rates were high. Achieving FPE was important for an mRS score of 0-2, even in patients with successful recanalization.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Masculino , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugía , Estudios Prospectivos , Trombectomía , Resultado del Tratamiento , Infarto Cerebral , Estudios Retrospectivos , StentsRESUMEN
Cranioplasty-related reperfusion injury has rarely been reported. Although there are several hypotheses, particularly regarding the mechanisms of the event, clear evidence is lacking. Here, we report the case of an 84-year-old man with traumatic intracranial hemorrhage and subdural hematoma who underwent decompressive craniectomy and hematoma evacuation in the right hemisphere. After 45 days, cranioplasty was performed using titanium. A preoperative perfusion study with 99m-Tc-HMPAO brain single-photon emission tomography revealed diffuse hypoperfusion in the left cerebral hemisphere with decreased vascular reserve. After cranioplasty, multiple cerebral hemorrhages were observed on immediate postoperative computed tomography. Cerebral hemorrhage eventually improved without surgery. Here, we report a case with findings revealed through perfusion studies before and after surgery.
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OBJECTIVE: Endovascular treatment of large, wide-necked intracranial aneurysms by coil embolization is often complicated by low rates of complete occlusion and high rates of recurrence. A flow diverter device has been shown to be safe and effective for the treatment of not only large and giant unruptured aneurysms, but small and medium aneurysms. However, in Korea, its use has only recently been approved for aneurysms <10 mm. This study aims to compare the safety and efficacy of flow diversion and coil embolization for the treatment of unruptured aneurysms ≥7 mm. METHODS: The participants will include patients aged between 19 and 75 years to be treated for unruptured cerebral aneurysms ≥7 mm for the first time or for recurrent aneurysms after initial endovascular coil embolization. Participants assigned to a flow diversion cohort will be treated using any of the following devices : Pipeline Flex Embolization Device with Shield Technology (Medtronic, Minneapolis, MN, USA), Surpass Evolve (Stryker Neurovascular, Fremont, CA, USA), and FRED or FRED Jr. (MicroVention, Tustin, CA, USA). Participants assigned to a coil embolization cohort will undergo traditional endovascular coiling. The primary endpoint will be complete occlusion confirmed by cerebral angiography at 12 months after treatment. Secondary safety outcomes will evaluate periprocedural and post-procedural complications for up to 12 months. RESULTS: The trial will begin enrollment in 2022, and clinical data will be available after enrollment and follow-up. CONCLUSION: This article describes the aim and design of a multi-center, randomized, open-label trial to compare the safety and efficacy of flow diversion versus traditional endovascular treatment for unruptured cerebral aneurysms ≥7 mm.