Journal of Cerebral Blood Flow and Metabolism最新文献_第8页

Neuronal deterioration associated with hyperexcitability under mild chronic cerebral hypoperfusion. 轻度慢性脑灌注不足下神经元退化与高兴奋性相关。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-15 DOI: 10.1177/0271678X251328971

Takuya Urushihata, Manami Takahashi, Masafumi Shimojo, Yuhei Takado, Nobuhiro Nitta, Yosuke Tajima, Kazuto Masamoto, Iwao Kanno, Yutaka Tomita, Naruhiko Sahara, Masaya Takahashi, Takayuki Obata, Hiroshi Ito, Tetsuro Yamashita, Tetsuya Suhara, Makoto Higuchi, Hiroyuki Takuwa

{"title":"Neuronal deterioration associated with hyperexcitability under mild chronic cerebral hypoperfusion.","authors":"Takuya Urushihata, Manami Takahashi, Masafumi Shimojo, Yuhei Takado, Nobuhiro Nitta, Yosuke Tajima, Kazuto Masamoto, Iwao Kanno, Yutaka Tomita, Naruhiko Sahara, Masaya Takahashi, Takayuki Obata, Hiroshi Ito, Tetsuro Yamashita, Tetsuya Suhara, Makoto Higuchi, Hiroyuki Takuwa","doi":"10.1177/0271678X251328971","DOIUrl":"https://doi.org/10.1177/0271678X251328971","url":null,"abstract":"Chronic cerebral hypoperfusion (CCH) has been indicated to impair cognitive and diverse brain functions. However, the neural mechanisms linking these cerebrovascular and phenotypic alterations remain unclear. Here, we investigated the effect of CCH on neuronal activity in male mice with unilateral common carotid artery occlusion using optical imaging and MRI. Our examinations revealed enhanced neuronal activity in concurrence with increased glutamate and tissue acidosis up to seven days after occlusion. At 21-28 days after occlusion, neuronal activity decreased below baseline, while the acidotic but not the hyperglutamatergic state persisted. Notably, pharmacological blockade of the N-methyl-D-aspartate-type glutamate receptor, initiated at an early stage of CCH, suppressed the onset of neuronal hyperexcitation and subsequent deficits in neuronal activity. Altogether, we provide experimental evidence that CCH induces a glutamate surge and results in neuronal hyperexcitation at an early phase, which thereafter gives rise to a non-lethal but progressive deterioration of neuronal functions.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251328971"},"PeriodicalIF":4.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078332","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

Combination of alpha-1 antitrypsin (A1AT) and anti-TNFα as a neuroprotective strategy in the early stages after ischemic stroke. α -1抗胰蛋白酶（A1AT）联合抗tnf α作为缺血性脑卒中早期的神经保护策略

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-15 DOI: 10.1177/0271678X251340234

Paula García-Rodríguez, Laura Ramiro, Alba Simats, Feifei Ma, Anna Rosell, Joan Montaner

{"title":"Combination of alpha-1 antitrypsin (A1AT) and anti-TNFα as a neuroprotective strategy in the early stages after ischemic stroke.","authors":"Paula García-Rodríguez, Laura Ramiro, Alba Simats, Feifei Ma, Anna Rosell, Joan Montaner","doi":"10.1177/0271678X251340234","DOIUrl":"10.1177/0271678X251340234","url":null,"abstract":"Neuroprotection after ischemic stroke has been focused on targeting one pathway of the ischemic cascade. In this study, we have hypothesized that combination therapy with alpha-1 antitrypsin (A1AT) and a blocker of tumor necrosis factor (TNFα) could be beneficial in the acute phases after ischemia. Following a detailed safety assessment of the co-administration of both drugs, we tested their neuroprotective effect in a transient mouse model of proximal middle cerebral artery occlusion (MCAo) by evaluating infarct extension and functional outcomes. Anti-TNFα (20 mg/kg) and A1AT were administered at different doses (ranging from 60 mg/kg to 700 mg/kg), as a single therapy during occlusion or at different time-points following reperfusion. Results showed that the administration of A1AT (60 mg/kg) in combination with anti-TNFα (20 mg/kg) was safe and effective when given during occlusion by reducing infarct volume at 24 h by 27% compared with the vehicle group (p = 0.0001). In conclusion, the synergy of the anti-apoptotic and anti-inflammatory properties of both drugs can reduce infarct volume in a stroke mouse model when given in the hyperacute phase. This approach shows promise as an early intervention strategy for stroke patients and underscores the potential of drug repurposing to develop new stroke treatments.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251340234"},"PeriodicalIF":4.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078288","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

Sickle cell mice exhibit elevated plasma bilirubin and altered intracranial cerebral blood velocities that are exacerbated by hypoxia-reoxygenation. 镰状细胞小鼠表现出血浆胆红素升高和颅内脑血流速度改变，缺氧再氧化加剧了这种变化。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-15 DOI: 10.1177/0271678X251338961

Francisco J Nunez, Ashraf M Mohieldin, Amy Y Pan, Sean P Palecek, Rahima Zennadi, Ramani Ramchandran, Kevin R Rarick, Surya M Nauli

{"title":"Sickle cell mice exhibit elevated plasma bilirubin and altered intracranial cerebral blood velocities that are exacerbated by hypoxia-reoxygenation.","authors":"Francisco J Nunez, Ashraf M Mohieldin, Amy Y Pan, Sean P Palecek, Rahima Zennadi, Ramani Ramchandran, Kevin R Rarick, Surya M Nauli","doi":"10.1177/0271678X251338961","DOIUrl":"https://doi.org/10.1177/0271678X251338961","url":null,"abstract":"Sickle cell disease (SCD) is a genetic disorder characterized by sickle red blood cells (RBCs). Sickle RBCs cause cerebral vasculopathies including vaso-occlusive events, leading to ischemia-reperfusion injury and hypoxic tissue environment. To date, the physiological blood flow velocities in cerebral vessels of preclinical SCD models has not been evaluated under hypoxic-reoxygenation. In our study, we used transcranial ultrasound techniques to measure abnormal blood flow velocities in the internal carotid (ICA) and middle cerebral arteries (MCA) of transgenic sickle cell mice (SS) challenged with hypoxia-reoxygenation. Our study showed that SS mice that underwent hypoxic stress exhibited lower relative mean velocities in the MCA compared to wildtype mice (AA) (0.67 ± 0.18 vs. 0.95 ± 0.15; p < 0.05). Comparison of the Lindegaard ratio between normoxia and hypoxia in SS mice suggested that the MCA underwent vasodilation (0.67 ± 0.18 vs. 0.95 ± 0.15; p < 0.05). Bilirubin, a potential biomarker for cerebral vasculopathies in SCD, was higher in SS than AA mice (0.56<math><mo> </mo><mo>±</mo><mo> </mo></math>0.28 vs. 0.05<math><mo> </mo><mo>±</mo><mo> </mo></math>0.07 mg/dL; p < 0.05). Correlation analyses revealed a significant association between bilirubin levels and blood velocities of MCA (r = -0.9377, p = 0.0002) and ICA (r = 0.8203, p = 0.0068), especially in hypoxic conditions of SS mice. We propose that the reactivity of cerebral vessels in SS mice is correlated with the elevated plasma bilirubin level.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251338961"},"PeriodicalIF":4.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078377","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

Amyloid beta peptides inhibit glucose transport at the blood-brain barrier by disrupting the insulin-AKT pathway. 淀粉样肽通过破坏胰岛素- akt通路抑制葡萄糖在血脑屏障的转运。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-15 DOI: 10.1177/0271678X251332493

Lushan Wang, Geoffry L Curran, Rui Zhong, Zheng Xue, Vaishnavi Veerareddy, Josslen Thieschafer, Paul H Min, Ling Li, Val J Lowe, Karunya K Kandimalla

{"title":"Amyloid beta peptides inhibit glucose transport at the blood-brain barrier by disrupting the insulin-AKT pathway.","authors":"Lushan Wang, Geoffry L Curran, Rui Zhong, Zheng Xue, Vaishnavi Veerareddy, Josslen Thieschafer, Paul H Min, Ling Li, Val J Lowe, Karunya K Kandimalla","doi":"10.1177/0271678X251332493","DOIUrl":"10.1177/0271678X251332493","url":null,"abstract":"Molecular mechanisms underlying disruptions in brain glucose uptake and metabolism, linked with cognitive decline in Alzheimer's disease (AD) patients, are only partially understood. This study investigated how soluble amyloid beta (sAβ) peptides affect glucose transport at the blood-brain barrier (BBB), the primary portal for glucose entry into the brain. We demonstrated that [18F]-fluorodeoxyglucose (18FDG) uptake is reduced in sAβ overproducing APP,PS1 transgenic mice compared to wild-type mice. Moreover, the influx rate of 18FDG decreased in sAβ40 or sAβ42 pre-infused mice, highlighting the inhibitory effect of sAβ peptides on glucose transport at the BBB. Consistently, the expression of GLUT1, the primary glucose transporter at the BBB, is reduced in polarized human cerebral microvascular endothelial cell (hCMEC/D3) monolayers upon exposure to sAβ peptides and in Aβ-laden cerebral vasculature in vivo. The study further examined the influence of sAβ on the insulin-AKT pathway, known to regulate glucose uptake through modulation of thioredoxin-interacting protein (TXNIP) expression. Results showed that sAβ peptides suppress AKT phosphorylation and reduce GLUT1 expression by upregulating TXNIP levels in hCMEC/D3 monolayers. Co-incubation of resveratrol with sAβ peptides reduced TXNIP expression and rectified reductions in GLUT1 expression. In summary, toxic sAβ impairs BBB glucose transport by disrupting the insulin/AKT/TXNIP axis.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251332493"},"PeriodicalIF":4.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078282","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 4.9 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

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

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

Correlation of zero echo time functional MRI with neuronal activity in rats. 零回声时间功能性MRI与大鼠神经元活动的相关性。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-01 Epub Date: 2025-01-23 DOI: 10.1177/0271678X251314682

Juha S Valjakka, Jaakko Paasonen, Raimo A Salo, Ekaterina Paasonen, Petteri Stenroos, Irina Gureviciene, Mikko Kettunen, Djaudat Idiyatullin, Heikki Tanila, Shalom Michaeli, Silvia Mangia, Olli Gröhn

{"title":"Correlation of zero echo time functional MRI with neuronal activity in rats.","authors":"Juha S Valjakka, Jaakko Paasonen, Raimo A Salo, Ekaterina Paasonen, Petteri Stenroos, Irina Gureviciene, Mikko Kettunen, Djaudat Idiyatullin, Heikki Tanila, Shalom Michaeli, Silvia Mangia, Olli Gröhn","doi":"10.1177/0271678X251314682","DOIUrl":"10.1177/0271678X251314682","url":null,"abstract":"Zero echo time (zero-TE) pulse sequences provide a quiet and artifact-free alternative to conventional functional magnetic resonance imaging (fMRI) pulse sequences. The fast readouts (<1 ms) utilized in zero-TE fMRI produce an image contrast with negligible contributions from blood oxygenation level-dependent (BOLD) mechanisms, yet the zero-TE contrast is highly sensitive to brain function. However, the precise relationship between the zero-TE contrast and neuronal activity has not been determined. Therefore, we aimed to derive a function to model the temporal dynamics of the zero-TE fMRI signal in response to neuronal activity. Furthermore, we examined the correlation of zero-TE fMRI with neuronal activity across stimulation frequencies. To these ends, we performed simultaneous electrophysiological recordings and zero-TE fMRI in rats subjected to whisker stimulation. The presented impulse response function provides a basis for the statistical modeling of neuronal activity-induced changes in the zero-TE fMRI signal. The temporal characteristics of the zero-TE fMRI response were found to be consistent with the previously postulated non-BOLD hemodynamic origin of the functional contrast. The zero-TE fMRI signal was well predicted by electrophysiological recordings, although systematic stimulation-dependent residuals were also observed, suggesting nonlinearities in neurovascular coupling. We conclude that zero-TE fMRI provides a robust proxy for neuronal activity.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"855-870"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023558","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