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Background@#and Purpose Previous studies have revealed the diverse neuroprotective effects of GV1001. In this study, we investigated the effects of GV1001 on focal cerebral ischemia-reperfusion injury (IRI) in rats and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in neural stem cells (NSCs) and cortical neurons. @*Methods@#Focal cerebral IRI was induced by transient middle cerebral artery occlusion (MCAO). Brain diffusion-weighted imaging (DWI) was performed 2 hours after occlusion, and a total of 37 rats were treated by reperfusion with GV1001 or saline 2 hours after occlusion. Fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging, immunohistochemistry, and neurobehavioral function analyses were performed. Additionally, OGD/R-injured NSCs and cortical neurons were treated with different GV1001 concentrations. Cell viability, proliferation, migration, and oxidative stress were determined by diverse molecular analyses. @*Results@#In the stroke model, GV1001 protected neural cells against IRI. The most effective dose of GV1001 was 60 μM/kg. The infarct volume on FLAIR 48 hours after MCAO compared to lesion volume on DWI showed a significantly smaller ratio in the GV1001-treated group. GV1001-treated rats exhibited better behavioral functions than the saline-treated rats. Treatment with GV1001 increased the viability, proliferation, and migration of the OGD/R-injured NSCs. Free radicals were significantly restored by treatment with GV1001. These neuroprotective effects of GV1001 have also been demonstrated in OGD/R-injured cortical neurons. Conclusions The results suggest that GV1001 has neuroprotective effects against IRI in NSCs, cortical neurons, and the rat brain. These effects are mediated through the induction of cellular proliferation, mitochondrial stabilization, and anti-apoptotic, anti-aging, and antioxidant effects.
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Objective@#: Hemorrhagic transformation (HT) can be occurred after acute cerebral infarction. HT can worse symptoms in severe cases and adversely affect long-term prognosis. As bone and vascular smooth muscle are composed of type 1 collagen, we aimed to identify a potential relationship between bone mineral density (BMD) and HT after acute cardioembolic stroke. @*Methods@#: As an indicator of BMD, we used mean frontal skull Hounsfield unit (HU) values on brain computed tomography (CT). Multivariative hazard ratios were calculated using Cox regression analysis to identify whether the osteoporotic condition was an independent predictor of HT after acute cardioembolic stroke. @*Results@#: This 11-year analysis enrolled 506 patients who diagnosed as acute cardioembolic infarction. The first tertile of skull HU value was an independent predictor of HT development compared to the third tertile (hazard ratio, 2.12; 95% confidence interval, 1.13–3.98; p=0.020). We observed no interactions between age and skull HU with respect to HT statistically. @*Conclusion@#: The results of this study revealed an association between osteoporotic conditions and HT development after acute cardioembolic stroke. A convenient method to measure the cancellous bone HU value of the frontal skull using brain CT images may be useful for predicting HT in patients with acute cerebral infarction.
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Background@#and Purpose: Neural stem cells (NSCs) have the ability to regenerate, proliferate, and differentiate, enabling them to play important roles in the recovery of the damaged nervous system. However, in neurodegenerative diseases such as Alzheimer's disease (AD), the NSCs are damaged as well. Glia-like cells from human mesenchymal stem cells (ghMSCs) are functionally enhanced adult stem cells. In the present study, we investigated whether ghMSCs could protect NSCs from amyloid beta (Aβ)-mediated toxicity. @*Methods@#Rat NSCs were obtained from E13–14 fetal rat cortices. NSCs were seeded in pre-coated plates, and the next day, cells were simultaneously treated with 20 μM Aβ and 0.4 μm pore insert well-seeded ghMSCs. After 48 hours of co-treatment, cell viability and proliferation were evaluated. After 2 hours of co-treatment, western blotting was performed to measure inflammasome-related factors, such as NOD-like receptor family pyrin domain containing 3, caspase-1, and interleukin-1β. @*Results@#The results showed that ghMSCs increased viability and proliferation and reduced the toxicity of NSCs injured by Aβ by reducing the NRLP3 inflammasome activation of NSCs induced by Aβ. @*Conclusions@#In this study, we confirmed that ghMSCs could protect NSCs in an in vitro model of AD through the regulation of inflammatory response.
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Background@#and Purpose Previous studies have revealed the diverse neuroprotective effects of GV1001. In this study, we investigated the effects of GV1001 on focal cerebral ischemia-reperfusion injury (IRI) in rats and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in neural stem cells (NSCs) and cortical neurons. @*Methods@#Focal cerebral IRI was induced by transient middle cerebral artery occlusion (MCAO). Brain diffusion-weighted imaging (DWI) was performed 2 hours after occlusion, and a total of 37 rats were treated by reperfusion with GV1001 or saline 2 hours after occlusion. Fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging, immunohistochemistry, and neurobehavioral function analyses were performed. Additionally, OGD/R-injured NSCs and cortical neurons were treated with different GV1001 concentrations. Cell viability, proliferation, migration, and oxidative stress were determined by diverse molecular analyses. @*Results@#In the stroke model, GV1001 protected neural cells against IRI. The most effective dose of GV1001 was 60 μM/kg. The infarct volume on FLAIR 48 hours after MCAO compared to lesion volume on DWI showed a significantly smaller ratio in the GV1001-treated group. GV1001-treated rats exhibited better behavioral functions than the saline-treated rats. Treatment with GV1001 increased the viability, proliferation, and migration of the OGD/R-injured NSCs. Free radicals were significantly restored by treatment with GV1001. These neuroprotective effects of GV1001 have also been demonstrated in OGD/R-injured cortical neurons. Conclusions The results suggest that GV1001 has neuroprotective effects against IRI in NSCs, cortical neurons, and the rat brain. These effects are mediated through the induction of cellular proliferation, mitochondrial stabilization, and anti-apoptotic, anti-aging, and antioxidant effects.
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Objective@#: Hemorrhagic transformation (HT) can be occurred after acute cerebral infarction. HT can worse symptoms in severe cases and adversely affect long-term prognosis. As bone and vascular smooth muscle are composed of type 1 collagen, we aimed to identify a potential relationship between bone mineral density (BMD) and HT after acute cardioembolic stroke. @*Methods@#: As an indicator of BMD, we used mean frontal skull Hounsfield unit (HU) values on brain computed tomography (CT). Multivariative hazard ratios were calculated using Cox regression analysis to identify whether the osteoporotic condition was an independent predictor of HT after acute cardioembolic stroke. @*Results@#: This 11-year analysis enrolled 506 patients who diagnosed as acute cardioembolic infarction. The first tertile of skull HU value was an independent predictor of HT development compared to the third tertile (hazard ratio, 2.12; 95% confidence interval, 1.13–3.98; p=0.020). We observed no interactions between age and skull HU with respect to HT statistically. @*Conclusion@#: The results of this study revealed an association between osteoporotic conditions and HT development after acute cardioembolic stroke. A convenient method to measure the cancellous bone HU value of the frontal skull using brain CT images may be useful for predicting HT in patients with acute cerebral infarction.
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Background@#and Purpose: Neural stem cells (NSCs) have the ability to regenerate, proliferate, and differentiate, enabling them to play important roles in the recovery of the damaged nervous system. However, in neurodegenerative diseases such as Alzheimer's disease (AD), the NSCs are damaged as well. Glia-like cells from human mesenchymal stem cells (ghMSCs) are functionally enhanced adult stem cells. In the present study, we investigated whether ghMSCs could protect NSCs from amyloid beta (Aβ)-mediated toxicity. @*Methods@#Rat NSCs were obtained from E13–14 fetal rat cortices. NSCs were seeded in pre-coated plates, and the next day, cells were simultaneously treated with 20 μM Aβ and 0.4 μm pore insert well-seeded ghMSCs. After 48 hours of co-treatment, cell viability and proliferation were evaluated. After 2 hours of co-treatment, western blotting was performed to measure inflammasome-related factors, such as NOD-like receptor family pyrin domain containing 3, caspase-1, and interleukin-1β. @*Results@#The results showed that ghMSCs increased viability and proliferation and reduced the toxicity of NSCs injured by Aβ by reducing the NRLP3 inflammasome activation of NSCs induced by Aβ. @*Conclusions@#In this study, we confirmed that ghMSCs could protect NSCs in an in vitro model of AD through the regulation of inflammatory response.
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Background@#and Purpose: The incidence of ischemic stroke (IS) in young adults is increasing, and the associated large socioeconomic impact makes understanding IS in young adults important. We investigated the causes of and risk factors for IS in young adults, and their impact on outcomes. @*Methods@#The Stroke in Korean Young Adults (SKY) study is a standardized multicenter prospective study involving eight medical centers of the Republic of Korea. First-ever IS patients aged 18 years to 44 years were prospectively included in this study within 7 days of stroke onset.Their outcomes at 3 months were analyzed. @*Results@#This study enrolled 270 patients from April 2014 to December 2018, most (67.8%) of whom were male. About 41.5% of the patients had one or more vascular risk factors from among hypertension, diabetes mellitus, and dyslipidemia. However, only half of them had received regular treatment. Arterial dissection was more common in males, and systemic lupus erythematosus (SLE) and Moyamoya disease were more common in females. The outcome was favorable (modified Rankin Scale score of 0 or 1) in 81.9% of the patients at 3 months after stroke onset. More severe initial symptoms, higher initial glucose level, and SLE as a comorbidity were associated with unfavorable outcomes. @*Conclusions@#Young adult IS patients in Korea exhibit low awareness and poor management of their risk factors. Although the short-term outcome was relatively favorable in those patients, having SLE was associated with unfavorable outcomes. More attention needs to be paid for improving awareness and controlling risk factors in this population.
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Background@#and Purpose: The aim of this study was to investigate the effects of multicomponent exercise on cognitive function, depression, and quality of life in elderly individuals. @*Methods@#This study prospectively recruited 605 participants, and constructed an exercise pyramid comprising even distributions of daily physical activities, aerobic exercise, musclestrengthening exercise, flexibility exercise, balance exercise, and activities that subjects could perform while sitting down. The exercise program was divided into six stages according to the participant’s level of frailty. The 12-week exercise program intervention was conducted once yearly. @*Results@#The exercise regimen was followed by 402 of the 605 enrolled participants, giving a dropout rate of 33.6%. The 27-month exercise program was completed by 60 participants.The scores for the Mini Mental State Examination for dementia screening (MMSE-DS), short form of the Geriatric Depression Scale, World Health Organization Quality of Life Assessment (WHOQOL-BREF), International Physical Activity Questionnaire (IPAQ), fear of falling, handgrip strength, and walking speed were improved after the exercise intervention. The analysis of frailty revealed that participants in the frail group showed greater improvements for the MMSE-DS, WHOQOL-BREF, IPAQ, fear of falling, handgrip strength, and walking speed. @*Conclusions@#Individually customized, multicomponent exercise programs lead to improved levels of cognitive function, depression, and quality of life, especially among those who are more frail.
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No abstract available.
Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis , Diagnostic Tests, RoutineABSTRACT
No abstract available.
Subject(s)
Asymptomatic Diseases , Carotid Artery, Internal , Carotid Stenosis , FingersABSTRACT
The authors recently found a mistake in their previously published article.
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Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) has been reported to play critical roles in the proliferation of various cancer cells. However, the roles of LGR5 in brain tumors and the specific intracellular signaling proteins directly associated with it remain unknown. Expression of LGR5 was first measured in normal brain tissue, meningioma, and pituitary adenoma of humans. To identify the downstream signaling pathways of LGR5, siRNA-mediated knockdown of LGR5 was performed in SH-SY5Y neuroblastoma cells followed by proteomics analysis with 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE). In addition, the expression of LGR5-associated proteins was evaluated in LGR5-inhibited neuroblastoma cells and in human normal brain, meningioma, and pituitary adenoma tissue. Proteomics analysis showed 12 protein spots were significantly different in expression level (more than two-fold change) and subsequently identified by peptide mass fingerprinting. A protein association network was constructed from the 12 identified proteins altered by LGR5 knockdown. Direct and indirect interactions were identified among the 12 proteins. HSP 90-beta was one of the proteins whose expression was altered by LGR5 knockdown. Likewise, we observed decreased expression of proteins in the hnRNP subfamily following LGR5 knockdown. In addition, we have for the first time identified significantly higher hnRNP family expression in meningioma and pituitary adenoma compared to normal brain tissue. Taken together, LGR5 and its downstream signaling play critical roles in neuroblastoma and brain tumors such as meningioma and pituitary adenoma.
Subject(s)
Humans , Brain , Brain Neoplasms , Cell Proliferation , Dermatoglyphics , Electrophoresis, Polyacrylamide Gel , GTP-Binding Proteins , Heterogeneous-Nuclear Ribonucleoproteins , Intracellular Signaling Peptides and Proteins , Meningioma , Neuroblastoma , Pituitary Neoplasms , ProteomicsABSTRACT
Leucine-rich G protein-coupled receptor-5 (LGR5) is known to be a stem cell marker in many organs. LGR5 may have important roles in proliferative diabetic retinopathy (PDR) because LGR5 potentiate the Wnt/β-catenin pathway, which plays crucial roles in pathologic neovascularization in the retina. The association between LGR5 and retinal pathologic neovascularization has not yet been reported. In the present study, LGR5 was compared in human aqueous humor (AH) between normal control and patients with PDR to confirm the relationship between LGR5 and PDR. AH was collected from 7 naïve PDR patients and 3 control subjects before intravitreal injection and cataract surgery, respectively. LGR5 and key members of Wnt/β-catenin were assessed by western blotting. In the present study, it was confirmed for the first time that LGR5 is detected in AH and it increases in PDR patients. Key members of Wnt/β-catenin pathway were also increased in AH of PDR patients compared to control. These findings might support the hypothesis that LGR5 has important roles in PDR especially considering the roles of the Wnt/β-catenin pathway, which is activated by LGR5, contributing to retinal pathologic neovascularization.
Subject(s)
Humans , Aqueous Humor , Blotting, Western , Cataract , Diabetic Retinopathy , Intravitreal Injections , Neovascularization, Pathologic , Retina , Retinaldehyde , Stem Cells , Wnt Signaling PathwayABSTRACT
BACKGROUND AND PURPOSE: Carotid plaques are a strong risk factor for ischemic stroke, and plaque rupture poses an even higher risk. Although many studies have investigated the pathogenic mechanisms of carotid plaque formation, few have studied the differences in molecular mechanisms underlying the rupture and non-rupture of carotid plaques. In addition, since early diagnosis and treatment of carotid plaque rupture are critical for the prevention of ischemic stroke, many studies have sought to identify the important target molecules involved in the rupture. However, a target molecule critical in symptomatic ruptured plaques is yet to be identified. METHODS: A total of 79 carotid plaques were consecutively collected, and microscopically divided into ruptured and non-ruptured groups. Quantitative polymerase chain reaction array, proteomics, and immunohistochemistry were performed to compare the differences in molecular mechanisms between ruptured and non-ruptured plaques. Enzyme-linked immunosorbent assay was used to measure the differences in ATP-binding cassette subfamily A member 1 (ABCA1) levels in the serum. RESULTS: The expression of several mRNAs and proteins, including ABCA1, was higher in ruptured plaques than non-ruptured plaques. In contrast, the expression of other proteins, including β-actin, was lower in ruptured plaques than non-ruptured plaques. The increased expression of ABCA1 was consistent across several experiments, ABCA1 was positive only in the serum of patients with symptomatic ruptured plaques. CONCLUSIONS: This study introduces a plausible molecular mechanism underlying carotid plaque rupture, suggesting that ABCA1 plays a role in symptomatic rupture. Further study of ABCA1 is needed to confirm this hypothesis.
Subject(s)
Humans , Biomarkers , Carotid Arteries , Early Diagnosis , Enzyme-Linked Immunosorbent Assay , Immunohistochemistry , Polymerase Chain Reaction , Proteomics , Risk Factors , RNA, Messenger , Rupture , StrokeABSTRACT
BACKGROUND AND PURPOSE: Subclinical atherosclerotic plaques are common in patients with pontine infarctions (PIs) but without basilar artery (BA) stenosis. We hypothesized that BA plaque locations may differ by PI type and vertical location as well as vertebrobasilar artery geometry. METHODS: Ninety-six patients with PI but without BA stenosis on magnetic resonance imaging (MRI) and magnetic resonance angiography were enrolled. PIs were classified by type (paramedian, deep, or lateral) and vertical location (rostral, middle, or caudal). Patients underwent high-resolution MRI to evaluate BA plaque location (anterior, posterior, or lateral). The mid-BA angle on anteroposterior view and angle between the BA and dominant vertebral artery (BA-VA angle) on lateral view were measured. RESULTS: The PIs were paramedian (72.9%), deep (17.7%), and lateral (9.4%) type with a rostral (32.3%), middle (42.7%), and caudal (25.0%) vertical location. The BA plaque locations differed by PI type (P=0.03) and vertical location (P < 0.001); BA plaques were most frequent at the posterior wall in paramedian (37.1%) and caudal (58.3%) PIs and at the lateral wall in lateral (55.5%) and middle (34.1%) PIs. The BA-VA and mid-BA angles differed by BA plaque and PI vertical location; the greatest BA-VA angle was observed in patients with posterior plaques (P < 0.001) and caudal PIs (P<0.001). Greatest mid-BA angles were observed with lateral BA plaques (P=0.03) and middlelocated PIs (P=0.03). CONCLUSIONS: Greater mid-BA angulation may enhance lateral plaque formation, causing lateral and middle PIs, whereas greater BA-VA angulation may enhance posterior plaque formation, causing paramedian or caudal PIs.
Subject(s)
Humans , Arteries , Basilar Artery , Brain Stem Infarctions , Constriction, Pathologic , Hemodynamics , Infarction , Magnetic Resonance Angiography , Magnetic Resonance Imaging , Plaque, Atherosclerotic , Vertebral ArteryABSTRACT
BACKGROUND AND PURPOSE: The pathophysiology of post-stroke depression (PSD) is complex and may differ according to an individual’s mood immediately after stroke. Here, we compared the therapeutic response and clinical characteristics of PSD at a later stage between patients with and without depression immediately after stroke. METHODS: This study involved a post hoc analysis of data from EMOTION (ClinicalTrials.gov NCT01278498), a placebo-controlled, double-blind trial that examined the efficacy of escitalopram (10 mg/day) on PSD and other emotional disturbances among 478 patients with acute stroke. Participants were classified into the Baseline-Blue (patients with baseline depression at the time of randomization, defined per the Montgomery-Asberg Depression Rating Scale [MADRS] ≥8) or the Baseline-Pink groups (patients without baseline depression). We compared the efficacy of escitalopram and predictors of 3-month PSD (MADRS ≥8) between these groups. RESULTS: There were 203 Baseline-Pink and 275 Baseline-Blue patients. The efficacy of escitalopram in reducing PSD risk was more pronounced in the Baseline-Pink than in the Baseline-Blue group (p for interaction=0.058). Several risk factors differentially affected PSD development based on the presence of baseline depression (p for interaction < 0.10). Cognitive dysfunction was an independent predictor of PSD in the Baseline-Blue, but not in the Baseline-Pink group, whereas the non-use of escitalopram and being female were more strongly associated with PSD in the Baseline-Pink group. CONCLUSIONS: Responses to escitalopram and predictors of PSD 3 months following stroke differed based on the presence of baseline depression. Our data suggest that PSD pathophysiology is heterogeneous; therefore, different therapeutic strategies may be needed to prevent PSD emergence following stroke.
Subject(s)
Female , Humans , Affective Symptoms , Anger , Citalopram , Depression , Random Allocation , Risk Factors , StrokeABSTRACT
No abstract available.
Subject(s)
Physical Phenomena , Prostatitis , Helicobacter Infections , Helicobacter pylori , Central Serous Chorioretinopathy , Diabetes, Gestational , Ophthalmologists , Phosphatidylinositol 3-Kinases , Diagnosis, Differential , Physicians , Writing , Speech , Thinking , Prognosis , Otolaryngology , Internal Medicine , Pelvic Pain , Polyneuropathies , KoreaABSTRACT
Alzheimer's disease (AD) is the most common form of dementia. Although uncountable clinical trials have been done to develop the treatment of AD, there are a couple of drugs that can be used only for symptomatic treatment. Therefore, many studies based on the amyloid cascade hypothesis and the tauopathy hypothesis are still ongoing. After the failure of numerous huge Phase III clinical trials, arguments on those hypotheses have arisen and efforts to establish other possible therapeutic strategies based on diverse plausible mechanisms associated with AD have been done as well. One of the new therapeutic targets for AD is the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. In this review, questions on the two hypotheses, the definition of the PI3K/AKT pathway, the relationship between the pathway and AD, and the possibility of the modulation of the pathway as a new therapeutic strategy for AD will be discussed briefly.