Journal of Cerebral Blood Flow and Metabolism最新文献_第6页

Periprocedural therapeutics do not impair extracellular mitochondrial viability in transplantation. 围手术期治疗不会损害移植中细胞外线粒体活力。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-14 DOI: 10.1177/0271678X251340232

Francisco Javier Miralles, Keiko Lynne Prijoles, Ashtyn Winter, Michael R Levitt, Yasemin Sancak, Melanie Walker

{"title":"Periprocedural therapeutics do not impair extracellular mitochondrial viability in transplantation.","authors":"Francisco Javier Miralles, Keiko Lynne Prijoles, Ashtyn Winter, Michael R Levitt, Yasemin Sancak, Melanie Walker","doi":"10.1177/0271678X251340232","DOIUrl":"https://doi.org/10.1177/0271678X251340232","url":null,"abstract":"Mitochondrial transplantation is an emerging therapeutic approach for ischemia-reperfusion injury, offering the potential to restore cellular function through the engraftment of extracellular mitochondria. The successful clinical application of this strategy depends on the delivery of metabolically active mitochondria, yet the impact of circulating therapeutic agents on mitochondrial viability remains poorly understood. This study evaluates the effects of five clinically relevant agents commonly used during endovascular treatment of ischemic stroke-alteplase, cefazolin, lidocaine, phenylephrine, and heparinized saline-on extracellular mitochondria using an ex vivo model. Mitochondria were isolated from human skeletal muscle and mouse liver and exposed to these agents at clinically relevant and supra-physiological concentrations. Metabolic activity was assessed using a resazurin reduction assay as an indicator of mitochondrial viability. Even at concentrations up to 8-fold above clinical exposure, none of the agents significantly impaired mitochondrial function. These findings provide critical toxicological data demonstrating the compatibility of commonly used therapeutics with mitochondrial transplantation, supporting the development of safer and more optimized clinical protocols.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251340232"},"PeriodicalIF":4.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic and diagnostic potential of extracellular vesicle (EV)-mediated intercellular transfer of mitochondria and mitochondrial components. 细胞外囊泡（EV）介导的线粒体和线粒体成分的细胞间转移的治疗和诊断潜力。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-14 DOI: 10.1177/0271678X251338971

Mingjin Wang, Weida Wang, Michael Chopp, Zheng Gang Zhang, Yi Zhang

{"title":"Therapeutic and diagnostic potential of extracellular vesicle (EV)-mediated intercellular transfer of mitochondria and mitochondrial components.","authors":"Mingjin Wang, Weida Wang, Michael Chopp, Zheng Gang Zhang, Yi Zhang","doi":"10.1177/0271678X251338971","DOIUrl":"https://doi.org/10.1177/0271678X251338971","url":null,"abstract":"Extracellular vesicles (EVs) facilitate the transfer of biological materials between cells throughout the body. Mitochondria, membrane-bound organelles present in the cytoplasm of nearly all eukaryotic cells, are vital for energy production and cellular homeostasis. Recent studies highlight the critical role of the transport of diverse mitochondrial content, such as mitochondrial DNA (mt-DNA), mitochondrial RNA (mt-RNA), mitochondrial proteins (mt-Prots), and intact mitochondria by small EVs (<200 nm) and large EVs (>200 nm) to recipient cells, where these cargos contribute to cellular and mitochondrial homeostasis. The interplay between EVs and mitochondrial components has significant implications for health, metabolic regulation, and potential as biomarkers. Despite advancements, the mechanisms governing EV-mitochondria crosstalk and the regulatory effect of mitochondrial EVs remain poorly understood. This review explores the roles of EVs and their mitochondrial cargos in health and disease, examines potential mechanisms underlying their interactions, and emphasizes the therapeutic potential of EVs for neurological and systemic conditions associated with mitochondrial dysfunction.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251338971"},"PeriodicalIF":4.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulation of synaptic mitochondria by extracellular vesicles and its implications for neuronal metabolism and synaptic plasticity. 细胞外囊泡对突触线粒体的调控及其对神经元代谢和突触可塑性的影响。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-14 DOI: 10.1177/0271678X251337630

Yuzhou Zeng, Anna Antoniou

{"title":"Regulation of synaptic mitochondria by extracellular vesicles and its implications for neuronal metabolism and synaptic plasticity.","authors":"Yuzhou Zeng, Anna Antoniou","doi":"10.1177/0271678X251337630","DOIUrl":"https://doi.org/10.1177/0271678X251337630","url":null,"abstract":"Mitochondrial metabolism in neurons is necessary for energetically costly processes like synaptic transmission and plasticity. As post-mitotic cells, neurons are therefore faced with the challenge of maintaining healthy functioning mitochondria throughout lifetime. The precise mechanisms of mitochondrial maintenance in neurons, and particularly in morphologically complex dendrites and axons, are not fully understood. Evidence from several biological systems suggests the regulation of cellular metabolism by extracellular vesicles (EVs), secretory lipid-enclosed vesicles that have emerged as important mediators of cell communication. In the nervous system, neuronal and glial EVs were shown to regulate neuronal circuit development and function, at least in part via the transfer of protein and RNA cargo. Interestingly, EVs have been implicated in diseases characterized by altered metabolism, such as cancer and neurodegenerative diseases. Furthermore, nervous system EVs were shown to contain proteins related to metabolic processes, mitochondrial proteins and even intact mitochondria. Here, we present the current knowledge of the mechanisms underlying neuronal mitochondrial maintenance, and highlight recent evidence suggesting the regulation of synaptic mitochondria by neuronal and glial cell EVs. We further discuss the potential implications of EV-mediated regulation of mitochondrial maintenance and function in neuronal circuit development and synaptic plasticity.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251337630"},"PeriodicalIF":4.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quantitation of regional distribution of antibodies in rat brain following systemic and intra-CNS administration. 全身和中枢神经系统内给药后大鼠脑内抗体区域分布的定量研究。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-13 DOI: 10.1177/0271678X251333536

Shengjia Wu, Hsien Wei Huang, Aditi Panchal, Ekram Ahmed Chowdhury, Dhaval K Shah

{"title":"Quantitation of regional distribution of antibodies in rat brain following systemic and intra-CNS administration.","authors":"Shengjia Wu, Hsien Wei Huang, Aditi Panchal, Ekram Ahmed Chowdhury, Dhaval K Shah","doi":"10.1177/0271678X251333536","DOIUrl":"10.1177/0271678X251333536","url":null,"abstract":"Antibody therapy has demonstrated great potential for treating central nervous system (CNS) disorders. Since therapeutic efficacy relies on sufficient exposure in specific brain regions, quantitative understanding of antibody distribution within the brain is crucial. Additionally, insights into antibody brain distribution help elucidate how pathological antibodies accumulate during encephalitis. Accordingly, this study investigated the regional distribution of a non-target-binding antibody (trastuzumab) and a brain-target-binding antibody (anti-NMDAR1) following systemic and intra-CNS administration in rats. After systemic administration, both antibodies showed similar distribution across brain regions, with the olfactory bulb exhibiting significantly higher concentrations. Other regions had comparable exposure, with the striatum or hippocampus showing the lowest exposure. Intra-CSF administration resulted in similar distribution patterns but achieved significantly higher concentrations than systemic administration. In contrast, intra-striatal administration led to diverse distribution, with the highest concentrations near the injection site. Calculations based on striatum and interstitial fluid (ISF) concentrations indicated antibody accumulation in the perivascular space after intra-CNS administration. Target binding influenced distribution primarily after intra-CSF administration, where anti-NMDAR1 showed lower ISF concentrations early and reduced CSF concentrations later. These findings provide valuable quantitative insights for optimizing brain-targeted antibody therapies and understanding pathological antibody distribution in CNS disorders.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251333536"},"PeriodicalIF":4.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neural and vascular contributions to sensory impairments in a human alpha-synuclein transgenic mouse model of Parkinson's disease. 在人类α -突触核蛋白转基因帕金森病小鼠模型中，神经和血管对感觉障碍的贡献。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-07 DOI: 10.1177/0271678X251338952

Ruxanda Lungu, Francisca F Fernandes, Sara Pires Monteiro, Tiago F Outeiro, Noam Shemesh

{"title":"Neural and vascular contributions to sensory impairments in a human alpha-synuclein transgenic mouse model of Parkinson's disease.","authors":"Ruxanda Lungu, Francisca F Fernandes, Sara Pires Monteiro, Tiago F Outeiro, Noam Shemesh","doi":"10.1177/0271678X251338952","DOIUrl":"https://doi.org/10.1177/0271678X251338952","url":null,"abstract":"Parkinson's disease (PD) is a complex progressive neurodegenerative disorder involving hallmarks such as <math><mi>α</mi></math>-Synuclein (<math><mi>α</mi></math>Syn) aggregation and dopaminergic dysfunction that affect brain-wide neural activity. Although movement disorders are prominent in PD, sensory impairments also occur relatively early on, mainly in olfactory and, to a lesser extent visual systems. While these deficits have been described mainly at the behavioral and molecular levels, the underlying network-level activity remains poorly understood. Here, we harnessed a human <math><mi>α</mi></math>Syn transgenic mouse model of PD with in vivo functional MRI (fMRI) to map evoked activity in the visual and olfactory pathways, along with pseudo-Continuous Arterial Spin Labeling (pCASL) and c-FOS measurements to disentangle vascular from neuronal effects. Upon stimulation with either odors or flickering lights, we found significant decreases in fMRI responses along both olfactory and visual pathways, in multiple cortical and subcortical sensory areas. Average Cerebral Blood Flow rates were decreased by ∼10% in the <math><mi>α</mi></math>Syn group, while c-FOS levels were reduced by over 50%, suggesting a strong neural driver for the dysfunction, along with more modest vascular contributions. Our study provides insight into brain-level activity in an <math><mi>α</mi></math>Syn-based model, and suggests a novel target for biomarking via quantification of simple sensory evoked responses.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251338952"},"PeriodicalIF":4.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elucidating stroke etiology through lipidomics of thrombi and plasma in acute ischemic stroke patients undergoing endovascular thrombectomy. 通过血管内取栓术急性缺血性卒中患者血栓和血浆脂质组学研究卒中病因。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-05 DOI: 10.1177/0271678X251327944

Chih-Ning Cheng, Chung-Wei Lee, Ching-Hua Lee, Sung-Chun Tang, Ching-Hua Kuo

{"title":"Elucidating stroke etiology through lipidomics of thrombi and plasma in acute ischemic stroke patients undergoing endovascular thrombectomy.","authors":"Chih-Ning Cheng, Chung-Wei Lee, Ching-Hua Lee, Sung-Chun Tang, Ching-Hua Kuo","doi":"10.1177/0271678X251327944","DOIUrl":"https://doi.org/10.1177/0271678X251327944","url":null,"abstract":"Acute ischemic stroke (AIS) requires detailed etiology information to guide optimal management. Given the pivotal role of lipids in AIS, we conducted a comprehensive lipidomics analysis of paired thrombi and plasma from AIS patients, correlating the findings with stroke etiology. Patients were recruited across four etiologies: cardioembolism (CE), large artery atherosclerosis (LAA), active cancer (Cancer), and undetermined. Plasma and thrombi were collected before and during endovascular thrombectomy and analyzed using in-house targeted lipidomics. Among 51 patients (37 CE, 7 LAA, 4 Cancer, and 3 undetermined), we identified 37 and 70 lipid species significantly different between thrombi in CE and LAA, and CE and Cancer, respectively (FDR-corrected P < 0.05). No significant differences were observed in plasma. Notably, 21 diacylglycerols and 11 polyunsaturated triacylglycerols were depleted (2.5 to 12 folds) in LAA compared to CE, while 10 ceramides and 57 glycerophospholipids were elevated in Cancer. With 80% validation accuracy, 29 and 59 lipids distinguished LAA and Cancer from CE, respectively. A neural network model using these lipids effectively classified undetermined patients. This study emphasizes the significance of thrombus lipids in distinguishing between LAA, CE, and Cancer etiologies in AIS, enhancing our understanding of stroke pathophysiology and informing future clinical managements.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251327944"},"PeriodicalIF":4.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cerebral small vessel disease: The impact of glymphopathy and sleep disorders. 脑血管疾病：淋巴病变与睡眠障碍的影响。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-05 DOI: 10.1177/0271678X251333933

Zaw Myo Hein, Che Mohd Nasril Che Mohd Nassir, Muhammad Danial Che Ramli, Usman Jaffer, Muhammad Zulfadli Mehat, Muzaimi Mustapha, Hafizah Abdul Hamid

{"title":"Cerebral small vessel disease: The impact of glymphopathy and sleep disorders.","authors":"Zaw Myo Hein, Che Mohd Nasril Che Mohd Nassir, Muhammad Danial Che Ramli, Usman Jaffer, Muhammad Zulfadli Mehat, Muzaimi Mustapha, Hafizah Abdul Hamid","doi":"10.1177/0271678X251333933","DOIUrl":"https://doi.org/10.1177/0271678X251333933","url":null,"abstract":"The glymphatic system, a vital brain perivascular network for waste clearance, hinges on the functionality of the aquaporin 4 (AQP4) water channel. Alarmingly, AQP4 single nucleotide polymorphisms (SNPs) are linked to impaired glymphatic clearance, or glymphopathy, which contributes to sleep disturbances and various age-related neurodegenerative diseases. Despite the critical role of glymphopathy and sleep disturbances in cerebral small vessel disease (CSVD) - a silent precursor to age-related neurodegenerative disorders - their interplay remains underexplored. CSVD is a major cause of stroke and dementia, yet its pathogenesis is not fully understood. Emerging evidence implicates glymphopathy and sleep disorders as pivotal factors in age-related CSVD, exacerbating the condition by hindering waste removal and compromising blood-brain barrier (BBB) integrity. Advanced imaging techniques promise to enhance diagnosis and monitoring, while lifestyle modifications and personalised medicine present promising treatment avenues. This narrative review underscores the need for a multidisciplinary approach to understanding glymphopathy and sleep disorders in CSVD. By exploring their roles, emphasising the necessity for longitudinal studies, and discussing potential therapeutic interventions, this paper aims to pave the way for new research and therapeutic directions in CSVD management.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251333933"},"PeriodicalIF":4.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Accurate and fully automated diameter measurements of Circle of Willis arteries on MRA imaging. 在MRA成像上精确全自动测量Willis动脉圈直径。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-05 DOI: 10.1177/0271678X251338972

Julia Huck, Davy Vanderweyen, Tatjana Rundek, Mitchell Sv Elkind, Jose Gutierrez, Maxime Descoteaux, Kevin Whittingstall

{"title":"Accurate and fully automated diameter measurements of Circle of Willis arteries on MRA imaging.","authors":"Julia Huck, Davy Vanderweyen, Tatjana Rundek, Mitchell Sv Elkind, Jose Gutierrez, Maxime Descoteaux, Kevin Whittingstall","doi":"10.1177/0271678X251338972","DOIUrl":"https://doi.org/10.1177/0271678X251338972","url":null,"abstract":"The Circle of Willis (CW), visualized via Magnetic Resonance Angiography (MRA), is crucial for assessing cerebral circulation. Accurate artery identification is essential not only for detecting stenosis and pathological changes but also for understanding vascular adaptations in healthy aging. Manual CW assessment is time-consuming, necessitating automated alternatives. This study evaluates intracranial artery diameter estimations from the Express IntraCranial Arteries Breakdown (eICAB) toolbox against manual measurements. eICAB was tested on 631 participants from the Northern Manhattan Study (NOMAS) with 1.5T MRA images (0.293 × 0.293 × 1 mm resolution). We analyzed eICAB's detection and diameter estimation accuracy of the Internal Carotid (ICA), Basilar (BA), Anterior Cerebral (ACA), Middle Cerebral (MCA), Posterior Cerebral (PCA), and Posterior Communicating (PCom). eICAB showed over 95% accuracy in detecting major arteries except for PCA and PCom (∼80%). Diameter discrepancies were generally ≤0.5 mm, with ICA and BA reaching 1 mm. Spearman correlation (p ≪ 0.05) confirmed strong agreement between automated and manual measurements. Resampling at 0.2083 mm improved precision. eICAB accurately identifies CW arteries and estimates diameters, demonstrating strong clinical and research potential.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251338972"},"PeriodicalIF":4.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neurological complications associated with chimeric antigen receptor T cell therapy. 与嵌合抗原受体T细胞治疗相关的神经系统并发症。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-02 DOI: 10.1177/0271678X251332492

Sijia Yan, Mi Zhou, Xiaojian Zhu, Yi Xiao

引用次数: 0

Upregulation of astrocytic mitochondrial functions via Korean red ginseng-induced CREB-BKα-HIF-1α axis through L-type Ca²⁺ channel subunits α1C and β4. 红参诱导的CREB-BKα-HIF-1α轴通过l型Ca2+通道亚基α1C和β4上调星形细胞线粒体功能

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-02 DOI: 10.1177/0271678X251332760

Hyungsu Kim, Sunhong Moon, Minsu Kim, Hyungkeun Oh, Jinhong Park, Suji Kim, Taehyung Yoo, Ji-Yoon Kim, Yonghee Kim, Young-Myeong Kim, Yoon Kyung Choi

{"title":"Upregulation of astrocytic mitochondrial functions via Korean red ginseng-induced CREB-BKα-HIF-1α axis through L-type Ca2+ channel subunits α1C and β4.","authors":"Hyungsu Kim, Sunhong Moon, Minsu Kim, Hyungkeun Oh, Jinhong Park, Suji Kim, Taehyung Yoo, Ji-Yoon Kim, Yonghee Kim, Young-Myeong Kim, Yoon Kyung Choi","doi":"10.1177/0271678X251332760","DOIUrl":"https://doi.org/10.1177/0271678X251332760","url":null,"abstract":"Korean red ginseng extract (KRGE) enhances astrocytic functions through hypoxia-inducible factor-1α (HIF-1α). Astrocytic Ca2+ influx through L-type Ca2+ channels (LTCCs) facilitates neurovascular communication, while the large-conductance Ca2+- and voltage-activated K+ (BK) channel mediates K+ efflux for vasodilation. However, the role of LTCC subunits in KRGE-mediated BKα and HIF-1α expression in astrocytes remains unclear. This study aimed to investigate the effects of KRGE on LTCC subunits, cytosolic Ca2+ influx, and BKα and HIF-1α induction in human astrocytes. The levels of BKα, LTCCs, and HIF-1α were analyzed in KRGE-treated mouse brain tissue using immunohistochemistry. Human astrocytes treated with an LTCC agonist exhibited increased BKα and HIF-1α protein levels. Similarly, KRGE increased the levels of LTCC subunits α1 C and β4, cytosolic Ca2+ influx, BKα, and HIF-1α. Moreover, knockdown of either α1 C or β4 attenuated KRGE-induced increases in Ca2+ influx and HIF-1α levels. Notably, their combined knockdown synergistically reduced KRGE-induced increases in BKα levels, mitochondrial mass, ATP production, and O2 consumption. The corpus callosum astrocytes of KRGE-treated mice exhibited increased levels of α1 C and β4, BKα, HIF-1α, and cAMP-response element binding protein (CREB). Collectively, these findings suggest that KRGE induced astrocytic BKα and HIF-1α expression via LTCC-mediated Ca2+ influx and subsequent CREB activation.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251332760"},"PeriodicalIF":4.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0