Journal of Cerebral Blood Flow and Metabolism最新文献

{"title":"Glucocorticoid signaling mediates lymphopoiesis impairment after cardiac arrest in mice.","authors":"Ángela Del Águila, Lihong Dang, Ran Zhang, Jin Zhang, Ata Ur Rehman, Feng Xu, Ashis Dhar, Xiao-Ping Zhong, Huaxin Sheng, Wei Yang","doi":"10.1177/0271678X251314321","DOIUrl":"10.1177/0271678X251314321","url":null,"abstract":"<p><p>Cardiac arrest (CA) is a life-threatening condition that requires immediate medical attention. Considerable advances in resuscitation have led to an increasing number of patients who survive the initial arrest event. However, among this growing patient population, morbidity and mortality rates remain strikingly high. This has been attributed to post-CA syndrome of which an imbalanced immune response is a crucial component. Using a murine CA model, we have shown that a profound immunosuppressive phase, characterized by severe lymphopenia, ensues following the initial pro-inflammatory response after CA. In the current study, we found that T and B lymphopoiesis was greatly impaired, as evidenced by the rapid and marked depletion of double-positive T cells and pre-B cells in the thymus and bone marrow, respectively. Our data then demonstrated that pharmacologic suppression of glucocorticoid signaling after CA significantly attenuated lymphopoiesis impairment, thereby mitigating post-CA lymphopenia. Lastly, we showed that specific deletion of the glucocorticoid receptor in T or B cells largely prevented the CA-induced depletion of immature lymphocyte populations in the thymus or bone marrow, respectively. Together, our findings indicate that glucocorticoid signaling mediates post-CA impairment of lymphopoiesis, a key contributor to post-CA immunosuppression.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251314321"},"PeriodicalIF":4.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006237","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}

{"title":"Circulating molecules reflect imaging biomarkers of hemorrhage in cerebral cavernous malformations.","authors":"Stephanie F Hage, Dehua E Bi, Serena Kinkade, Diana Vera Cruz, Abhinav Srinath, Aditya Jhaveri, Sharbel Romanos, Akash Bindal, Rhonda Lightle, Jessica C Little, Robert Shenkar, Roberto J Alcazar-Felix, Justine Lee, Agnieszka Stadnik, Ashley Sidebottom, Timothy J Carroll, Yuan Ji, Janne Koskimaki, Sean P Polster, Romuald Girard, Issam A Awad","doi":"10.1177/0271678X251314366","DOIUrl":"10.1177/0271678X251314366","url":null,"abstract":"<p><p>Increases in mean lesional iron content by quantitative susceptibility mapping (QSM) by ≥6% and/or vascular permeability by dynamic contrast enhanced quantitative perfusion (DCEQP) by ≥40% on MRI have been associated with new symptomatic hemorrhage (SH) in cerebral cavernous malformations (CCMs). It is not known if plasma biomarkers can reflect these changes within the lesion proper. This cohort study enrolled 46 CCM patients with SH in the prior year. Plasma samples, QSM and DCEQP were simultaneously acquired at the beginning and end of 60 one-year epochs of prospective follow-up. Plasma levels of 16 proteins and 12 metabolites linked to CCM hemorrhage were assessed by enzyme-linked immunosorbent assay and liquid-chromatography mass spectrometry, respectively. A weighted model combining the percent changes in plasma levels in roundabout guidance receptor-4, cluster of differentiation 14, thrombomodulin and acetyl-L-carnitine reflected a mean increase in QSM ≥ 6% (97.2% and 100% specificity/sensitivity, p = 3.1 × 10^-13). A weighted combination of percent changes in plasma levels of endoglin, pipecolic acid, arachidonic acid and hypoxanthine correlated with an increase in mean DCEQP ≥40% (99.6% specificity and 100% sensitivity, p = 4.1 × 10^-17). This is a first report linking with great accuracy changes of circulating molecules to imaging changes reflecting new SH during prospective follow-up of CCMs.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251314366"},"PeriodicalIF":4.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006228","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}

{"title":"Non-invasive [¹⁵O]H₂O PET measurements of cerebral perfusion and cerebrovascular reactivity using an additional heart scan.","authors":"Mathias Jacobsen Bach, Mia E Larsen, Amanda O Kellberg, Alexander C Henriksen, Stefan Fuglsang, Inge Lise Rasmussen, Markus Nowak Lonsdale, Mark Lubberink, Lisbeth Marner","doi":"10.1177/0271678X251313743","DOIUrl":"10.1177/0271678X251313743","url":null,"abstract":"<p><p>Obtaining the arterial input function (AIF) is essential for quantitative regional cerebral perfusion (rCBF) measurements using [¹⁵O]H₂O PET. However, arterial blood sampling is invasive and complicates the scanning procedure. We propose a new non-invasive dual scan technique with an image derived input function (IDIF) from an additional heart scan. Six patients and two healthy subjects underwent [¹⁵O]H₂O PET imaging of 1) heart and brain during baseline, and 2) heart and brain after infusion of acetazolamide. The IDIF was extracted from the left ventricle of the heart and compared to the AIF. The rCBF was compared for six bilateral cortical regions. AIFs and IDIFs showed strong agreement. rCBF with AIF and IDIF showed strong correlation for both baseline rCBF (R² = 0.99, slope = 0.89 CI: [0.87; 0.91], p < 0.0001) and acetazolamide rCBF (R² = 0.98, slope = 0.93, CI:[0.90;0.97], p < 0.0001) but showed a positive bias of 0.047 mL/(g·min) [-0.025; +0.119] for baseline and 0.024 [-1.04, +1.53] mL/(g·min) for acetazolamide. In conclusion, the invasive arterial cannulation can be replaced by an additional scan of the heart with a minor bias of rCBF estimation. The method is applicable to all scanner systems.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251313743"},"PeriodicalIF":4.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006240","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}

{"title":"Control of neurovascular coupling by ATP-sensitive potassium channels.","authors":"Ryan M Bowen, Nathaniel W York, Jonah Padawer-Curry, Adam Q Bauer, Jin-Moo Lee, Colin G Nichols","doi":"10.1177/0271678X251313906","DOIUrl":"10.1177/0271678X251313906","url":null,"abstract":"<p><p>Regional blood flow within the brain is tightly coupled to regional neuronal activity, a process known as neurovascular coupling (NVC). In this study, we demonstrate the striking role of SUR2- and Kir6.1-dependent ATP-sensitive potassium (K_ATP) channels in control of NVC in the sensory cortex of conscious mice, in response to mechanical stimuli. We demonstrate that either globally increased (pinacidil-activated) or decreased (glibenclamide-inhibited) K_ATP activity markedly disrupts NVC; pinacidil-activation is capable of completely abolishing stimulus-evoked cortical hemodynamic responses, while glibenclamide slows and reduces the response. The response is similarly slowed and reduced in SUR2 KO animals, while animals expressing gain-of-function (GOF) mutations in Kir6.1, which underlie Cantú syndrome, exhibit baseline reduction of NVC as well as increased sensitivity to pinacidil. In revealing the dramatic effects of either increasing or decreasing SUR2/Kir6.1-dependent K_ATP activity on NVC, whether pharmacologically or genetically induced, the study has important implications both for monogenic K_ATP channel diseases and for more common brain pathologies.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251313906"},"PeriodicalIF":4.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006233","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}

{"title":"Chronic high fat diet-induced cerebrovascular remodeling impairs recovery of blood flow after cerebral ischemia in mice.","authors":"Jun Li, Naidi Sun, Song Hu, Zhiyi Zuo","doi":"10.1177/0271678X251313723","DOIUrl":"10.1177/0271678X251313723","url":null,"abstract":"<p><p>Obesity and associated metabolic disturbances worsen brain ischemia outcome. High fat diet (HFD)-fed mice are obese and have cerebrovascular remodeling and worsened brain ischemia outcome. We determined whether HFD-induced cerebrovascular remodeling impaired reperfusion to the ischemic penumbra. Six-week-old C57BL/6J or matrix metalloprotease-9 knockout (MMP-9^-/-) mice were on HFD or regular diet (RD) for 12 to 14 months before a 60-min left middle cerebral arterial occlusion (MCAO). Photoacoustic microscopy was performed at left cerebral frontal cortex. HFD increased cerebrovascular density and tortuosity in C57BL/6J mice but not in MMP-9^-/- mice. Blood flow to the ischemic penumbra slowly recovered but did not reach the baseline 2 h after MCAO in RD-fed mice. Oxygen extraction fraction was increased to maintain cerebral metabolic rate of oxygen (CMRO₂) throughout brain ischemia and reperfusion period. This blood flow recovery was worsened in HFD-fed mice, leading to decreased CMRO₂. MMP-9^-/- attenuated these HFD effects. HFD increased MMP-9 activity and interleukin 1β. Pyrrolidine dithiocarbamate, an anti-inflammatory agent, abolished the HFD effects. Interleukin 1β increased MMP-9 activity. In summary, HFD induces cerebrovascular remodeling, leading to worsened recovery of blood supply to the ischemic penumbra to contribute to poor outcome after brain ischemia. Neuroinflammation may activate MMP-9 in HFD-fed mice.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251313723"},"PeriodicalIF":4.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006220","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}

{"title":"Characterizing astrocyte-mediated neurovascular coupling by combining optogenetics and biophysical modeling.","authors":"Alejandro Suarez, Lazaro Fernandez, Jorge Riera","doi":"10.1177/0271678X241311010","DOIUrl":"10.1177/0271678X241311010","url":null,"abstract":"<p><p>Vasoactive signaling from astrocytes is an important contributor to the neurovascular coupling (NVC), which aims at providing energy to neurons during brain activation by increasing blood perfusion in the surrounding vasculature. Pharmacological manipulations have been previously combined with experimental techniques (e.g., transgenic mice, uncaging, and multiphoton microscopy) and stimulation paradigms to isolate <i>in vivo</i> individual pathways of the astrocyte-mediated NVC. Unfortunately, these pathways are highly nonlinear and non-additive. To separate these pathways in a unified framework, we combine a comprehensive biophysical model of vasoactive signaling from astrocytes with a unique optogenetic stimulation method that selectively induces astrocytic Ca²⁺ signaling in a large population of astrocytes. We also use a sensitivity analysis and an optimization technique to estimate key model parameters. Optogenetically-induced Ca²⁺ signals in astrocytes cause a cerebral blood flow (CBF) response with two major components. Component-1 was rapid and smaller (ΔCBF∼13%, 18 seconds), while component-2 was slowest and highest (ΔCBF ∼18%, 45 seconds). The proposed biophysical model was adequate in reproducing component-2, which was validated with a pharmacological manipulation. Model's predictions were not in contradiction with previous studies. Finally, we discussed scenarios accounting for the existence of component-1, which once validated might be included in our model.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241311010"},"PeriodicalIF":4.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11719438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949613","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}

{"title":"Cerebral perfusion alterations in healthy young adults due to two genetic risk factors of Alzheimer's disease: APOE and MAPT.","authors":"Samuel K Bennett, Jianmin Zeng, Maria-Eleni Dounavi, Arshad Majid, Sheharyar S Baig, Matteo De Marco, Craig Ritchie, John T O'Brien, Li Su","doi":"10.1177/0271678X241310731","DOIUrl":"https://doi.org/10.1177/0271678X241310731","url":null,"abstract":"<p><p>Functional brain changes such as altered cerebral blood flow occur long before the onset of clinical symptoms in Alzheimer's disease (AD) and other neurodegenerative disorders. While cerebral hypoperfusion occurs in established AD, middle-aged carriers of genetic risk factors for AD, including APOE ε4, display regional hyperperfusion due to hypothesised pleiotropic or compensatory effects, representing a possible early biomarker of AD and facilitating earlier AD diagnosis. However, it is not clear whether hyperperfusion already exists even earlier in life. Here, 160 young and cognitively healthy participants from the Chinese PREVENT cohort underwent 3 T arterial spin labelling and T1 MRI and genetic testing for APOE and MAPT rs242557 status. Using FSL, we performed a whole brain voxel-wise analysis and a global mean grey matter analysis comparing for the effects of both risk genes on cerebral perfusion. No significant alterations were seen for APOE genotype, but in MAPT rs242557 A carriers, we observed a significantly hyperperfusion in the left anterior cingulate cortex and left insular cortex. There were no effects of APOE or MAPT status on the global perfusion. These results are novel and may suggest that MAPT genotypes demonstrated a distinct hemodynamic profile in a very young age.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241310731"},"PeriodicalIF":4.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949612","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}

{"title":"Association between cerebral oxygenation and usual parameters of cerebral perfusion in critically ill patients with acute brain injury.","authors":"Timothée Ayasse, Samuel Gaugain, Charles de Roquetaillade, Alexis Hermans-Didier, Manuel Kindermans, Benjamin G Chousterman, Romain Barthélémy","doi":"10.1177/0271678X241310780","DOIUrl":"10.1177/0271678X241310780","url":null,"abstract":"<p><p>In patients with acute brain injury (ABI), optimizing cerebral perfusion parameters relies on multimodal monitoring. This include data from systemic monitoring-mean arterial pressure (MAP), arterial carbon dioxide tension (PaCO₂), arterial oxygen saturation (SaO₂), hemoglobin levels (Hb), and temperature-as well as neurological monitoring-intracranial pressure (ICP), cerebral perfusion pressure (CPP), and transcranial Doppler (TCD) velocities. We hypothesized that these parameters alone were not sufficient to assess the risk of cerebral ischemia. We conducted a retrospective, single-center study of patients admitted in our ICU between 2015 and 2021. Patients with ABI and multimodal neuromonitoring were included. ABI included traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracranial hemorrhage and ischemic stroke. The relationship between jugular venous oxygen saturation (SjvO₂) and cerebral perfusion parameters was analyzed. Patients were categorized into two groups based on SjvO₂, with a threshold of 60% used to define cerebral ischemia. We compared the parameters used to optimize cerebral perfusion between groups and their diagnosis accuracy for cerebral ischemia was evaluated. Univariable and multivariable analyses were performed to assess the association between the guideline-recommended therapeutic targets and the risk of cerebral ischemia. 601 evaluations from 96 patients with simultaneous ICP, SjvO₂ and TCD were analyzed. Poor relationships were found between SjvO₂ and the parameters of cerebral perfusion. TCD flow velocities and PaCO₂ were lower in the cerebral ischemia group while MAP, ICP and CPP were not different between groups. Most ischemic episodes occurred despite ICP < 22 mmHg and CPP ≥ 60 mmHg. For the diagnosis of cerebral ischemia, only TCD parameters and PaCO₂ were associated with an area under the curve (AUC) > 0.5 but with a low accuracy. In multivariable analysis, the only guideline-recommended therapeutic target associated with a reduction of cerebral ischemia was a diastolic flow velocity (FV) > 20 cm.s^-1.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241310780"},"PeriodicalIF":4.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949611","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}

{"title":"Genetics of intracerebral hemorrhage.","authors":"Tamara N Kimball, Reinier Wp Tack, Anna Chen, Savvina Prapiadou, Jasper R Senff, Benjamin Yq Tan, Sanjula D Singh, Susanne J van Veluw, Steven M Greenberg, Jonathan Rosand, Christopher D Anderson","doi":"10.1177/0271678X241310401","DOIUrl":"https://doi.org/10.1177/0271678X241310401","url":null,"abstract":"<p><p>Spontaneous intracerebral hemorrhage(ICH) represents a life-threatening form of stroke, marked by its impact on survival and quality of life. ICH can be categorized from monogenic disorders linked to causal germline variants in ICH-related genes to complex sporadic cases, highlighting the interaction among lifestyle factors, environmental influences, and genetic components in determining risk. Among sporadic ICH, the influence of these factors varies across ICH subtypes, evidenced by heritability rates of up to 73% for lobar ICH versus 34% for non-lobar ICH. This review presents an outline of the genetic landscape of ICH, covering both monogenic and sporadic forms. It highlights associations between ICH risk and genetic variants, including rare and common variants in genes such as <i>COL4A1, COL4A2, APOE, ACE, MTHFR,</i> and <i>PMF1</i>. However, replication has been constrained, and most findings originate from single-candidate gene studies, largely due to ancestry heterogeneity, small sample sizes, and scarce subtype-specific data. To bridge this gap, collaborative efforts like the International Stroke Genetic Consortium have been established. Additionally, the review discusses the emerging role of polygenic risk scores, Mendelian randomization, and the potential of genetic and omics research to elucidate causal pathobiology. Such insights could lead to preventive measures and personalized ICH treatment strategies.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241310401"},"PeriodicalIF":4.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122850","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}

{"title":"Glutamine metabolism is systemically different between primary and induced pluripotent stem cell-derived brain microvascular endothelial cells.","authors":"Callie M Weber, Bilal Moiz, Marzyeh Kheradmand, Arielle Scott, Claire Kettula, Brooke Wunderler, Viviana Alpízar Vargas, Alisa Morss Clyne","doi":"10.1177/0271678X241310729","DOIUrl":"https://doi.org/10.1177/0271678X241310729","url":null,"abstract":"<p><p>Human primary (hpBMEC) and induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial-like cells (hiBMEC) are interchangeably used in blood-brain barrier models to study neurological diseases and drug delivery. Both hpBMEC and hiBMEC use glutamine as a source of carbon and nitrogen to produce metabolites and build proteins essential to cell function and communication. We used metabolomic, transcriptomic, and computational methods to examine how hpBMEC and hiBMEC metabolize glutamine, which may impact their utility in modeling the blood-brain barrier. We found that glutamine metabolism was systemically different between the two cell types. hpBMEC had a higher metabolic rate and produced more glutamate and GABA, while hiBMEC rerouted glutamine to produce more glutathione, fatty acids, and asparagine. Higher glutathione production in hiBMEC correlated with higher oxidative stress compared to hpBMEC. α-ketoglutarate (α-KG) supplementation increased glutamate secretion from hiBMEC to match that of hpBMEC; however, α-KG also decreased hiBMEC glycolytic rate. These fundamental metabolic differences between BMEC types may impact <i>in vitro</i> blood-brain barrier model function, particularly communication between BMEC and surrounding cells, and emphasize the importance of evaluating the metabolic impacts of iPSC-derived cells in disease models.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241310729"},"PeriodicalIF":4.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949614","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}