Journal of Cerebral Blood Flow and Metabolism最新文献_第10页

Unlocking the potential of photobiomodulation therapy for brain neurovascular coupling: The biological effects and medical applications. 释放光生物调节治疗脑神经血管耦合的潜力：生物学效应和医学应用。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-01 Epub Date: 2025-01-07 DOI: 10.1177/0271678X241311695

Bingzi Yan, Jie Zhou, Fengshuo Yan, Mingyang Gao, Jiaji Tang, Lin Huang, Yan Luo

引用次数: 0

Preclinical validation and kinetic modelling of the SV2A PET ligand [¹⁸F]UCB-J in mice. SV2A PET配体UCB-J在小鼠体内的临床前验证和动力学建模[18F]。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-01 Epub Date: 2024-12-04 DOI: 10.1177/0271678X241304923

Liesbeth Everix, Filipe Elvas, Alan Miranda Menchaca, Vinod Khetarpal, Longbin Liu, Jonathan Bard, Steven Staelens, Daniele Bertoglio

{"title":"Preclinical validation and kinetic modelling of the SV2A PET ligand [18F]UCB-J in mice.","authors":"Liesbeth Everix, Filipe Elvas, Alan Miranda Menchaca, Vinod Khetarpal, Longbin Liu, Jonathan Bard, Steven Staelens, Daniele Bertoglio","doi":"10.1177/0271678X241304923","DOIUrl":"10.1177/0271678X241304923","url":null,"abstract":"Synaptic vesicle protein 2A (SV2A) is ubiquitously expressed in presynaptic terminals where it functions as a neurotransmission regulator protein. Synaptopathy has been reported during healthy ageing and in a variety of neurodegenerative diseases. Positron emission tomography (PET) imaging of SV2A can be used to evaluate synaptic density. The PET ligand [11C]UCB-J has high binding affinity and selectivity for SV2A but has a short physical half-life due to the 11C isotope. Here we report the characterization and validation of its 18F-labeled equivalent, [18F]UCB-J, in terms of specificity, reproducibility and stability in C57BL/6J mice. Plasma analysis revealed at least one polar radiometabolite. Kinetic modelling was performed using a population-based metabolite corrected image-derived input function (IDIF). [18F]UCB-J showed relatively fast kinetics and a reliable measure of the IDIF-based volume of distribution (VT(IDIF)). [18F]UCB-J specificity for SV2A was confirmed through a levetiracetam blocking assay (50 to 200 mg/kg). Reproducibility of the VT(IDIF) was determined through test-retest analysis, revealing significant correlation (r2 = 0.773, p < 0.0001). Time-stability analyses indicate a scan duration of 60 min to be sufficient to obtain a reliable VT(IDIF). In conclusion, [18F]UCB-J is a selective SV2A ligand with optimal kinetics in mice. Further investigation is warranted for (pre)clinical applicability of [18F]UCB-J in synaptopathies.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"920-931"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11615906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769336","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

Neurochemical characterization of 5-HT_2AR partial agonists with simultaneous PET-MRI. 5-HT2AR部分激动剂的神经化学特征与同步PET-MRI。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-01 Epub Date: 2024-11-29 DOI: 10.1177/0271678X241302937

Frederick A Bagdasarian, Kristian Larsen, Hong Ping Deng, Patrick M Fisher, Joseph B Mandeville, Christin Y Sander, Hsiao-Ying Wey, Hanne D Hansen

{"title":"Neurochemical characterization of 5-HT2AR partial agonists with simultaneous PET-MRI.","authors":"Frederick A Bagdasarian, Kristian Larsen, Hong Ping Deng, Patrick M Fisher, Joseph B Mandeville, Christin Y Sander, Hsiao-Ying Wey, Hanne D Hansen","doi":"10.1177/0271678X241302937","DOIUrl":"10.1177/0271678X241302937","url":null,"abstract":"Understanding neuromodulatory effects of serotonin 2A receptor (5-HT2AR) agonists with diverse pharmacological profiles is relevant to advancing psychedelic-related drug applications. We performed simultaneous positron emission tomography (PET) and pharmacological magnetic resonance imaging (phMRI) in anesthetized nonhuman primates (NHP; N = 3) to examine partial agonists with varying 5-HT2AR affinities and selectivity profiles: psilocybin (30, 60, and 90 µg/kg), lisuride (5 µg/kg), and 25CN-NBOH (15 µg/kg). Receptor occupancy was assessed with [11C]MDL-100907 PET, and cerebral blood volume (CBV) changes were measured with phMRI. Mixed partial agonists psilocybin and lisuride evoked biphasic CBV responses, whereas the selective 25CN-NBOH produced monophasic CBV increases. Cortical occupancy for psilocybin plateaued at 60 µg/kg (32%), whereas a lower dose of lisuride (5 µg/kg) resulted in similar occupancy (31%). Administration of 25CN-NBOH resulted in lower occupancy (7%) but larger changes in CBV compared to psilocybin and lisuride. The associations between CBV and 5-HT2AR occupancy appear linear for lisuride and 25CN-NBOH, but not for psilocybin. We speculate that the temporal and spatial differences in hemodynamic responses of the three agonists could stem from mixed affinity profiles. This work provides an understanding of pharmacological impacts of mixed serotonergic agonists being pursued as therapeutics for psychiatric conditions, offering valuable insights for future drug applications and development strategies.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"908-919"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750929","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

Gut microbiota-mediated choline metabolism exacerbates cognitive impairment induced by chronic cerebral hypoperfusion. 肠道微生物介导的胆碱代谢加剧慢性脑灌注不足引起的认知障碍。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-01 Epub Date: 2024-12-24 DOI: 10.1177/0271678X241309777

Xiao Li, Yueran Ren, Xuxuan Gao, Huidi Wang, Jiafeng Zhang, Jiahui Xie, Jingru Liang, Boxin Zhao, Hongwei Zhou, Jia Yin

{"title":"Gut microbiota-mediated choline metabolism exacerbates cognitive impairment induced by chronic cerebral hypoperfusion.","authors":"Xiao Li, Yueran Ren, Xuxuan Gao, Huidi Wang, Jiafeng Zhang, Jiahui Xie, Jingru Liang, Boxin Zhao, Hongwei Zhou, Jia Yin","doi":"10.1177/0271678X241309777","DOIUrl":"10.1177/0271678X241309777","url":null,"abstract":"Chronic cerebral hypoperfusion (CCH) is a crucial mechanism causing vascular cognitive impairment (VCI). Choline is metabolized by gut microbiota into trimethylamine N-oxide (TMAO), a risk factor of cardiovascular diseases and cognitive impairment. However, the impact of choline-TMAO pathway on CCH-induced VCI is elusive. We performed a cross-sectional clinical study to investigate the relationship between the choline-TMAO pathway and cognitive outcome and used a bilateral common carotid artery occlusion rat model to explore the effect of a choline-rich diet on cognition and underlying mechanisms. Plasma choline and TMAO levels were negatively correlated with cognitive scores in CCH patients. A choline-rich diet exacerbated CCH-induced cognitive impairment by encouraging the proliferation of choline-metabolizing bacteria in the gut and subsequent generation of TMAO. The choline-TMAO pathway, mediated by gut microbiota, exacerbates cognitive impairment induced by CCH. Targeted dietary choline regulation based on gut microbiota modulation may ameliorate long-term cognitive impairment.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"989-1004"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884853","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

Genomics of stroke recovery and outcome. 脑卒中恢复和预后的基因组学研究。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-04-11 DOI: 10.1177/0271678X251332528

Arne G Lindgren

引用次数: 0

Long lasting argon neuroprotection in a non-human primate model of transient endovascular ischemic stroke. 短暂性血管内缺血性中风的非人类灵长类动物模型中持久的氩气神经保护作用。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-04-01 Epub Date: 2024-12-04 DOI: 10.1177/0271678X241297798

Sandra González Torrecilla, Alisée Delbrel, Laura Giacomino, David Meunier, Julien Sein, Luc Renaud, Pauline Brige, Philippe Garrigue, Jean Francois Hak, Benjamin Guillet, Hervé Brunel, Géraldine Farjot, Thomas Brochier, Lionel Velly

{"title":"Long lasting argon neuroprotection in a non-human primate model of transient endovascular ischemic stroke.","authors":"Sandra González Torrecilla, Alisée Delbrel, Laura Giacomino, David Meunier, Julien Sein, Luc Renaud, Pauline Brige, Philippe Garrigue, Jean Francois Hak, Benjamin Guillet, Hervé Brunel, Géraldine Farjot, Thomas Brochier, Lionel Velly","doi":"10.1177/0271678X241297798","DOIUrl":"10.1177/0271678X241297798","url":null,"abstract":"In the past decade, noble gases have emerged as highly promising neuroprotective agents. Previous studies have demonstrated the efficacy of argon neuroprotection in rodent models of cerebral ischemia. The objective of the present pre-clinical study was to confirm the neuroprotective effect of argon in a non-human primate model of endovascular ischemic stroke. Thirteen adult Macaca mulatta were subjected to a focal cerebral ischemia induced by a transient (90 min) middle cerebral artery occlusion (tMCAO). The monkeys were randomly allocated to a control group (n = 8) and an argon group (n = 5). Pre-mixed gas (40-60 oxygen-argon) was applied 30 min after the onset of tMCAO to 30 min after reperfusion. Infarct volumes were measured from the MRI scans conducted 1 hour and 1 month after the reperfusion. A clinical neurological assessment was performed 24 hours and 1 month after tMCAO. Our results show that Argon dramatically reduced ischemic core volume after ischemia compared to the control group with a long-lasting improvement of post-stroke infarct volume at 1 month. In addition, the neurological scale suggests a better prognosis in argon-treated animals without reaching the significance threshold. These pre-clinical results in gyrencephalic non-human primates support the potential use of this therapeutic approach for future clinical studies.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"643-654"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11615904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769322","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

Retinal microvascular phenotypes can track small vessel disease burden and CPAP treatment effectiveness in obstructive sleep apnea. 视网膜微血管表型可追踪阻塞性睡眠呼吸暂停患者的小血管疾病负担和 CPAP 治疗效果。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-04-01 Epub Date: 2024-11-02 DOI: 10.1177/0271678X241291958

Ylenia Giarratano, Elizabeth A Hill, Charlene Hamid, Stewart Wiseman, Calum Gray, Francesca M Chappell, Roberto Duarte Coello, Maria C Valdés-Hernández, Lucia Ballerini, Michael S Stringer, Michael J Thrippleton, Daniela Jaime Garcia, Xiaodi Liu, William Hewins, Yajun Cheng, Sandra E Black, Andrew Lim, Rosa Sommer, Joel Ramirez, Bradley J MacIntosh, Rosalind Brown, Fergus Doubal, Tom MacGillivray, Joanna M Wardlaw, Renata Riha, Miguel O Bernabeu

{"title":"Retinal microvascular phenotypes can track small vessel disease burden and CPAP treatment effectiveness in obstructive sleep apnea.","authors":"Ylenia Giarratano, Elizabeth A Hill, Charlene Hamid, Stewart Wiseman, Calum Gray, Francesca M Chappell, Roberto Duarte Coello, Maria C Valdés-Hernández, Lucia Ballerini, Michael S Stringer, Michael J Thrippleton, Daniela Jaime Garcia, Xiaodi Liu, William Hewins, Yajun Cheng, Sandra E Black, Andrew Lim, Rosa Sommer, Joel Ramirez, Bradley J MacIntosh, Rosalind Brown, Fergus Doubal, Tom MacGillivray, Joanna M Wardlaw, Renata Riha, Miguel O Bernabeu","doi":"10.1177/0271678X241291958","DOIUrl":"10.1177/0271678X241291958","url":null,"abstract":"Optical coherence tomography angiography (OCT-A) retinal imaging enables in vivo visualization of the retinal microvasculature that is developmentally related to the brain and can offer insight on cerebrovascular health. We investigated retinal phenotypes and neuroimaging markers of small vessel disease (SVD) in individuals with obstructive sleep apnoea (OSA). We enrolled 44 participants (mean age 50.1 ± SD 9.1 years) and performed OCT-A imaging before and after continuous positive airway pressure (CPAP) therapy. Pre-treatment analyses using a generalized estimating equations model adjusted for relevant covariates, revealed perivascular spaces (PVS) volume in basal ganglia associated with greater foveal vessel density (fVD) (p-value < 0.001), and smaller foveal avascular zone area (p-value = 0.01), whereas PVS count in centrum semiovale associated with lower retinal vessel radius (p-value = 0.02) and higher vessel tortuosity (p-value = 0.01). A reduction in retinal vessel radius was also observed with increased OSA severity (p-value = 0.05). Post-treatment analyses showed greater CPAP usage was associated with a decrease in fVD (p-value = 0.02), and increased retinal vessel radius (p-value = 0.01). The findings demonstrate for the first time the potential use of OCT-A to monitor CPAP treatment and its possible impact on both retinal and brain vascular health.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"690-702"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564530","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

Associations of life-course cardiovascular risk factors with late-life cerebral hemodynamics. 终生心血管风险因素与晚年脑血流动力学的关联。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-04-01 Epub Date: 2024-11-17 DOI: 10.1177/0271678X241301261

Mathijs Bj Dijsselhof, Jorina Holtrop, Sarah-Naomi James, Carole H Sudre, Kirsty Lu, Luigi Lorenzini, Lyduine E Collij, Catherine J Scott, Emily N Manning, David L Thomas, Marcus Richards, Alun D Hughes, David M Cash, Frederik Barkhof, Jonathan M Schott, Jan Petr, Henk Jmm Mutsaerts

{"title":"Associations of life-course cardiovascular risk factors with late-life cerebral hemodynamics.","authors":"Mathijs Bj Dijsselhof, Jorina Holtrop, Sarah-Naomi James, Carole H Sudre, Kirsty Lu, Luigi Lorenzini, Lyduine E Collij, Catherine J Scott, Emily N Manning, David L Thomas, Marcus Richards, Alun D Hughes, David M Cash, Frederik Barkhof, Jonathan M Schott, Jan Petr, Henk Jmm Mutsaerts","doi":"10.1177/0271678X241301261","DOIUrl":"10.1177/0271678X241301261","url":null,"abstract":"While the associations of mid-life cardiovascular risk factors with late-life white matter lesions (WMH) and cognitive decline have been established, the role of cerebral haemodynamics is unclear. We investigated the relation of late-life (69-71 years) arterial spin labelling (ASL) MRI-derived cerebral blood flow (CBF) with life-course cardiovascular risk factors (36-71 years) and late-life white matter hyperintensity (WMH) load in 282 cognitively healthy participants (52.8% female). Late-life (69-71 years) high systolic (B = -0.15) and diastolic (B = -0.25) blood pressure, and mean arterial pressure (B = -0.25) were associated with low grey matter (GM) CBF (p < 0.03), and white matter CBF (B = -0.25; B = -0.15; B = -0.13, p < 0.03, respectively). The association between systolic blood pressure and GM CBF differed between sexes (male/female B = -0.15/0.02, p = 0.04). No associations were found with early- or mid-life cardiovascular risk factors. Furthermore, WMHs were associated with cerebral haemodynamics but not cardiovascular risk factors. These findings suggest that cerebral blood flow autoregulation is able to maintain stable global cerebral haemodynamics until later in life. Future studies are encouraged to investigate why cardiovascular risk factors have differential effects on haemodynamics and WMH, and their implications for cognitive decline.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"765-778"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647468","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

Evidence for cellular and solute passage between the brain and skull bone marrow across meninges: A systematic review. 脑和颅骨骨髓间细胞和溶质通过脑膜的证据：一项系统综述。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-04-01 Epub Date: 2025-01-25 DOI: 10.1177/0271678X251316392

Helena Eide Therkelsen, Rune Enger, Per Kristian Eide, Geir Ringstad

{"title":"Evidence for cellular and solute passage between the brain and skull bone marrow across meninges: A systematic review.","authors":"Helena Eide Therkelsen, Rune Enger, Per Kristian Eide, Geir Ringstad","doi":"10.1177/0271678X251316392","DOIUrl":"10.1177/0271678X251316392","url":null,"abstract":"A potential two-way passage of cells and substances between the brain and skull bone marrow may open for new insights into neurological disease. The arachnoid membrane was traditionally considered to restrict cells and larger molecules in CSF from entering the dura and bone marrow directly. However, new data on exchange between brain and skull bone marrow have recently emerged. Here, we conducted a systematic literature to answer the question: What is the current evidence regarding the movement of cells and molecules between the brain and skull bone marrow, spanning CSF and meninges? We excluded studies related to head or skull trauma, cranial fractures or defects, cancer invasion, CSF leakage, spontaneous intracranial hypotension, spinal dura mater, and studies solely focusing on meningeal lymphatic vessels or the passage of substances from CSF to meningeal lymphatic vessels. The review identified 16 studies that provide evidence of communication between the brain, meninges and skull bone marrow. Cells (such as B and T cells and neutrophils), bacteria, and substances (tracers, drug compounds) have been reported to pass between the brain and skull bone. However, most studies are performed in rodents, emphasizing the need for translation to humans.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"581-599"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038943","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

Pretreatment with oleuropein protects the neonatal brain from hypoxia-ischemia by inhibiting apoptosis and neuroinflammation. 通过抑制细胞凋亡和神经炎症，油菜素预处理可保护新生儿大脑免受缺氧缺血的影响。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-04-01 Epub Date: 2024-08-19 DOI: 10.1177/0271678X241270237

Marta Reyes-Corral, Laura Gil-González, Ángela González-Díaz, Javier Tovar-Luzón, María Irene Ayuso, Miguel Lao-Pérez, Joan Montaner, Rocío de la Puerta, Rut Fernández-Torres, Patricia Ybot-González

{"title":"Pretreatment with oleuropein protects the neonatal brain from hypoxia-ischemia by inhibiting apoptosis and neuroinflammation.","authors":"Marta Reyes-Corral, Laura Gil-González, Ángela González-Díaz, Javier Tovar-Luzón, María Irene Ayuso, Miguel Lao-Pérez, Joan Montaner, Rocío de la Puerta, Rut Fernández-Torres, Patricia Ybot-González","doi":"10.1177/0271678X241270237","DOIUrl":"10.1177/0271678X241270237","url":null,"abstract":"Hypoxic-ischemic (HI) encephalopathy is a cerebrovascular injury caused by oxygen deprivation to the brain and remains a major cause of neonatal mortality and morbidity worldwide. Therapeutic hypothermia is the current standard of care but it does not provide complete neuroprotection. Our aim was to investigate the neuroprotective effect of oleuropein (Ole) in a neonatal (seven-day-old) mouse model of HI. Ole, a secoiridoid found in olive leaves, has previously shown to reduce damage against cerebral and other ischemia/reperfusion injuries. Here, we administered Ole as a pretreatment prior to HI induction at 20 or 100 mg/kg. A week after HI, Ole significantly reduced the infarct area and the histological damage as well as white matter injury, by preserving myelination, microglial activation and the astroglial reactive response. Twenty-four hours after HI, Ole reduced the overexpression of caspase-3 and the proinflammatory cytokines IL-6 and TNF-α. Moreover, using UPLC-MS/MS we found that maternal supplementation with Ole during pregnancy and/or lactation led to the accumulation of its metabolite hydroxytyrosol in the brains of the offspring. Overall, our results indicate that pretreatment with Ole confers neuroprotection and can prevent HI-induced brain damage by modulating apoptosis and neuroinflammation.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"717-734"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000020","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