Journal of Cerebral Blood Flow and Metabolism最新文献

Therapeutic mitochondria treatment amplifies macrophage-mediated phagocytosis and recycling exocytosis. 治疗性线粒体处理可扩大巨噬细胞介导的吞噬作用和循环外吞作用。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-02-01 Epub Date: 2025-03-13 DOI: 10.1177/0271678X251326871

Masayoshi Tanaka, Shin Ishikane, Dong Bin Back, Ester Licastro, Fang Zhang, Ji Hyun Park, Elga Esposito, Giuseppe Pignataro, Takafumi Nakano, Yoshihiko Nakamura, Kazuhide Hayakawa

{"title":"Therapeutic mitochondria treatment amplifies macrophage-mediated phagocytosis and recycling exocytosis.","authors":"Masayoshi Tanaka, Shin Ishikane, Dong Bin Back, Ester Licastro, Fang Zhang, Ji Hyun Park, Elga Esposito, Giuseppe Pignataro, Takafumi Nakano, Yoshihiko Nakamura, Kazuhide Hayakawa","doi":"10.1177/0271678X251326871","DOIUrl":"10.1177/0271678X251326871","url":null,"abstract":"Therapeutic administration of mitochondria has been increasingly explored. However, how these administered mitochondria impact immune response remains to be fully addressed. In this proof-of-concept study, we show that extracellularly added mitochondria to cultured peritoneal macrophages increase phagocytosis and recycling exocytosis that amplifies neuroplasticity mediated by recycled mitochondria transfer. Macrophage activation markers such as Nos2, Arg1, and Cd163 were unchanged at 3 h post-treatment with mitochondria, but whole mitochondria or delivery of mRNAs extracted from whole mitochondria appeared to increase SQSTM1 protein and activate Nrf2-mediated phagocytosis in macrophages, whereas mitochondria treatment did not change the ability of phagocytosis in cultured microglia or astrocytes. Notably, the once engulfed mitochondria in macrophages appear to be released via Rab27a-mediated recycling pathway that were favorably incorporated in mechanically damaged neurons compared with healthy neurons, resulting in accelerating neurite extension in damaged neurons in a direct co-culture model. Altogether, these findings uncover unappreciated mechanisms that mitochondria-treated macrophages upregulate phagocytosis and recycling exocytosis, implicating that engineering mitochondria delivery to macrophages is a new therapeutic intervention to promote neurorecovery in CNS disorders.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"406-417"},"PeriodicalIF":4.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624829","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

Mitochondrial unfolded protein response (UPR^mt) as novel therapeutic targets for neurological disorders. 线粒体未折叠蛋白反应（UPRmt）作为神经系统疾病的新治疗靶点。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-02-01 Epub Date: 2025-05-15 DOI: 10.1177/0271678X251341293

Xi Chen, Hong An, Jiachen He, Jiaqi Guo, Shuaili Xu, Chuanjie Wu, Di Wu, Xunming Ji

{"title":"Mitochondrial unfolded protein response (UPRmt) as novel therapeutic targets for neurological disorders.","authors":"Xi Chen, Hong An, Jiachen He, Jiaqi Guo, Shuaili Xu, Chuanjie Wu, Di Wu, Xunming Ji","doi":"10.1177/0271678X251341293","DOIUrl":"10.1177/0271678X251341293","url":null,"abstract":"Neurological disorders, including brain cancer, neurodegenerative diseases and ischemic/reperfusion injury, pose a significant threat to global human health. Due to the high metabolic demands of nerve cells, mitochondrial dysfunction is a critical feature of these disorders. The mitochondrial unfolded protein response (UPRmt) is an evolutionarily conserved mitochondrial response, which is critical for maintaining mitochondrial and energetic homeostasis under stress. Previous studies have found that UPRmt participates in diverse physiological processes especially metabolism and immunity. Currently, increasing evidence suggest that targeted regulation of UPRmt can also effectively delay the progression of neurological diseases and improve patients' prognosis. This review provides a comprehensive overview of UPRmt in the context of neurological diseases, with a particular emphasis on its regulatory functions. Additionally, we summarize the mechanistic insights into UPRmt in neurological disorders as investigated in preclinical studies, as well as its potential as a therapeutic target in the clinical management of neurological tumors. By highlighting the importance of UPRmt in the complex processes underlying neurological disorders, this review aims to bridge current knowledge gaps and inspire novel therapeutic strategies for these conditions.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"333-349"},"PeriodicalIF":4.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078366","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

Molecular and cellular mechanisms of mitochondria transfer in models of central nervous system disease. 中枢神经系统疾病模型中线粒体转移的分子和细胞机制。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-02-01 Epub Date: 2024-11-14 DOI: 10.1177/0271678X241300223

Takafumi Nakano, Keiichi Irie, Koichi Matsuo, Kenichi Mishima, Yoshihiko Nakamura

{"title":"Molecular and cellular mechanisms of mitochondria transfer in models of central nervous system disease.","authors":"Takafumi Nakano, Keiichi Irie, Koichi Matsuo, Kenichi Mishima, Yoshihiko Nakamura","doi":"10.1177/0271678X241300223","DOIUrl":"10.1177/0271678X241300223","url":null,"abstract":"In the central nervous system (CNS), neuronal function and dysfunction are critically dependent on mitochondrial integrity and activity. In damaged or diseased brains, mitochondrial dysfunction reduces adenosine triphosphate (ATP) levels and impairs ATP-dependent neural firing and neurotransmitter dynamics. Restoring mitochondrial capacity to generate ATP may be fundamental in restoring neuronal function. Recent studies in animals and humans have demonstrated that endogenous mitochondria may be released into the extracellular environment and transported or exchanged between cells in the CNS. Under pathological conditions in the CNS, intercellular mitochondria transfer contributes to new classes of signaling and multifunctional cellular activities, thereby triggering deleterious effects or promoting beneficial responses. Therefore, to take full advantage of the beneficial effects of mitochondria, it may be useful to transplant healthy and viable mitochondria into damaged tissues. In this review, we describe recent findings on the mechanisms of mitochondria transfer and provide an overview of experimental methodologies, including tissue sourcing, mitochondrial isolation, storage, and modification, aimed at optimizing mitochondria transplantation therapy for CNS disorders. Additionally, we examine the clinical relevance and potential strategies for the therapeutic application of mitochondria transplantation.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"269-288"},"PeriodicalIF":4.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620958","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

Astrocytic mitochondrial transfer to brain endothelial cells and pericytes in vivo increases with aging. 体内星形细胞线粒体向脑内皮细胞和周细胞的转移随着年龄的增长而增加。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-02-01 Epub Date: 2024-12-12 DOI: 10.1177/0271678X241306054

Gopal V Velmurugan, Hemendra J Vekaria, Samir P Patel, Patrick G Sullivan, W Brad Hubbard

{"title":"Astrocytic mitochondrial transfer to brain endothelial cells and pericytes in vivo increases with aging.","authors":"Gopal V Velmurugan, Hemendra J Vekaria, Samir P Patel, Patrick G Sullivan, W Brad Hubbard","doi":"10.1177/0271678X241306054","DOIUrl":"10.1177/0271678X241306054","url":null,"abstract":"Intercellular mitochondrial transfer (IMT) is an intriguing biological phenomenon where mitochondria are transferred between different cells and notably, cell types. IMT is physiological, occurring in normal conditions, but also is utilized to deliver healthy mitochondria to cells in distress. Transferred mitochondria can be integrated to improve cellular metabolism, and mitochondrial function. Research on the mitochondrial transfer axis between astrocytes and brain capillaries in vivo is limited by the cellular heterogeneity of the neurovascular unit. To this end, we developed an inducible mouse model that expresses mitochondrial Dendra2 only in astrocytes and then isolated brain capillaries to remove all intact astrocytes. This method allows the visualization of in vivo astrocyte- endothelial cell (EC) and astrocyte-pericyte IMT. We demonstrate evidence of astrocyte-EC and astrocyte-pericyte mitochondrial transfer within brain capillaries. We also show that healthy aging enhances mitochondrial transfer from astrocytes to brain capillaries, revealing a potential link between brain aging and cellular mitochondrial dynamics. Finally, we observe that astrocyte-derived extracellular vesicles transfer mitochondria to brain microvascular endothelial cells, showing the potential route of in vivo IMT. These results represent a breakthrough in our understanding of IMT in the brain and a new target in brain aging and neurovascular metabolism.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"418-429"},"PeriodicalIF":4.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818221","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

Mitochondria transfer for myelin repair. 线粒体移植促进髓鞘修复

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-02-01 Epub Date: 2025-03-13 DOI: 10.1177/0271678X251325805

Sabah Mozafari, Luca Peruzzotti-Jametti, Stefano Pluchino

{"title":"Mitochondria transfer for myelin repair.","authors":"Sabah Mozafari, Luca Peruzzotti-Jametti, Stefano Pluchino","doi":"10.1177/0271678X251325805","DOIUrl":"10.1177/0271678X251325805","url":null,"abstract":"Demyelination is a common feature of neuroinflammatory and degenerative diseases of the central nervous system (CNS), such as multiple sclerosis (MS). It is often linked to disruptions in intercellular communication, bioenergetics and metabolic balance accompanied by mitochondrial dysfunction in cells such as oligodendrocytes, neurons, astrocytes, and microglia. Although current MS treatments focus on immunomodulation, they fail to stop or reverse demyelination's progression. Recent advancements highlight intercellular mitochondrial exchange as a promising therapeutic target, with potential to restore metabolic homeostasis, enhance immunomodulation, and promote myelin repair. With this review we will provide insights into the CNS intercellular metabolic decoupling, focusing on the role of mitochondrial dysfunction in neuroinflammatory demyelinating conditions. We will then discuss emerging cell-free biotherapies exploring the therapeutic potential of transferring mitochondria via biogenic carriers like extracellular vesicles (EVs) or synthetic liposomes, aimed at enhancing mitochondrial function and metabolic support for CNS and myelin repair. Lastly, we address the key challenges for the clinical application of these strategies and discuss future directions to optimize mitochondrial biotherapies. The advancements in this field hold promise for restoring metabolic homeostasis, and enhancing myelin repair, potentially transforming the therapeutic landscape for neuroinflammatory and demyelinating diseases.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"250-268"},"PeriodicalIF":4.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624820","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

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 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-02-01 Epub 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":"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":"350-358"},"PeriodicalIF":4.5,"publicationDate":"2026-02-01","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

Autologous mitochondrial transplant for acute cerebral ischemia: Phase 1 trial results and review. 自体线粒体移植治疗急性脑缺血：一期试验结果和回顾。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-02-01 Epub Date: 2024-12-04 DOI: 10.1177/0271678X241305230

Melanie Walker, Michael R Levitt, Emma M Federico, Francisco Javier Miralles, Sam Hs Levy, Keiko Lynne Prijoles, Ashtyn Winter, Jennifer K Swicord, Yasemin Sancak

{"title":"Autologous mitochondrial transplant for acute cerebral ischemia: Phase 1 trial results and review.","authors":"Melanie Walker, Michael R Levitt, Emma M Federico, Francisco Javier Miralles, Sam Hs Levy, Keiko Lynne Prijoles, Ashtyn Winter, Jennifer K Swicord, Yasemin Sancak","doi":"10.1177/0271678X241305230","DOIUrl":"10.1177/0271678X241305230","url":null,"abstract":"The results of a Phase 1 trial of autologous mitochondrial transplantation for the treatment of acute ischemic stroke during mechanical thrombectomy are presented. Standardized methods were used to isolate viable autologous mitochondria in the acute clinical setting, allowing for timely transplantation within the ischemic window. No significant adverse events were observed with the endovascular approach during reperfusion therapy. Safety outcomes in study participants were comparable to those of matched controls who did not undergo transplantation. This study represents the first use of mitochondrial transplantation in the human brain, highlighting specific logistical challenges related to the acute clinical setting, such as limited tissue samples and constrained time for isolation and transplantation. We also review the opportunities and challenges associated with further clinical translation of mitochondrial transplantation in the context of acute cerebral ischemia and beyond.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"322-332"},"PeriodicalIF":4.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11615905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769314","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 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-02-01 Epub 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":"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":"289-305"},"PeriodicalIF":4.5,"publicationDate":"2026-02-01","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 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-02-01 Epub 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":"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":"236-249"},"PeriodicalIF":4.5,"publicationDate":"2026-02-01","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

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 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-02-01 Epub 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":"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":"430-443"},"PeriodicalIF":4.5,"publicationDate":"2026-02-01","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