{"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":"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":"1082-1099"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","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}
Mathias Jacobsen Bach, Mia E Larsen, Amanda O Kellberg, Alexander C Henriksen, Stefan Fuglsang, Inge Lise Rasmussen, Markus Nowak Lonsdale, Mark Lubberink, Lisbeth Marner
{"title":"Non-invasive [<sup>15</sup>O]H<sub>2</sub>O 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 [<sup>15</sup>O]H<sub>2</sub>O 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 [<sup>15</sup>O]H<sub>2</sub>O 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 (R<sup>2</sup> = 0.99, slope = 0.89 CI: [0.87; 0.91], p < 0.0001) and acetazolamide rCBF (R<sup>2</sup> = 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":"1144-1152"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","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":"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<sup>-/-</sup>) 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<sup>-/-</sup> 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 (CMRO<sub>2</sub>) throughout brain ischemia and reperfusion period. This blood flow recovery was worsened in HFD-fed mice, leading to decreased CMRO<sub>2</sub>. MMP-9<sup>-/-</sup> 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":"1116-1129"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","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}
Hanna Schenck, Céline van Craenenbroeck, Sander van Kuijk, Erik Gommer, Michael Veldeman, Yasin Temel, Marcel Aries, Werner Mess, Roel Haeren
{"title":"Systematic review and meta-analysis of transcranial doppler biomarkers for the prediction of delayed cerebral ischemia following subarachnoid hemorrhage.","authors":"Hanna Schenck, Céline van Craenenbroeck, Sander van Kuijk, Erik Gommer, Michael Veldeman, Yasin Temel, Marcel Aries, Werner Mess, Roel Haeren","doi":"10.1177/0271678X251313746","DOIUrl":"10.1177/0271678X251313746","url":null,"abstract":"<p><p>Delayed cerebral ischemia (DCI) following an aneurysmal subarachnoid hemorrhage (aSAH) significantly impacts mortality, morbidity, and healthcare costs. This study assessed the diagnostic accuracy of Transcranial Doppler (TCD)-derived biomarkers for predicting DCI via a systematic review and meta-analysis. Included studies had to correctly define DCI and report data on sensitivity, specificity, positive predictive value, and negative predictive value. Univariate or bivariate analyses with a random effects model were used, and risk of bias was evaluated with the Quality Assessment of Diagnostic Accuracy Studies. From 23 eligible articles (n = 2371 patients), three biomarker categories were identified: cerebral blood flow velocities (CBFV), cerebral autoregulation, and microembolic signals (MES). The highest sensitivity (0.86, 95% CI 0.71-0.94) and specificity (0.75, 95% CI 0.52-0.94) for DCI prediction were achieved with a mean CBFV of 120 cm/s combined with a Lindegaard ratio. The transient hyperemic response test showed the best performance among autoregulatory biomarkers with a sensitivity of 0.88, (95% CI 0.54-0.98) and specificity of 0.82 (95% CI 0.52-0.94). MES were less effective predictors. Combining CBFV with autoregulatory biomarkers enhanced TCD's predictive value. High heterogeneity and risk of bias were noted, indicating the need for a standardized TCD approach for improved DCI evaluation.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1031-1047"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663604","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}
Richard S Beard, Brian A Hoettels, Jessica M McAllister, Jamie E Meegan, Travis S Wertz, Desiree A Self, Dylan E Hrkach, Daniel Greiner, Kristina Chapman, Nuria Villalba, Xiaoyuan Yang, Byeong J Cha, Cheryl L Jorcyk, Julia T Oxford, Mack H Wu, Sarah Y Yuan
{"title":"Progression of experimental autoimmune encephalomyelitis in mice and neutrophil-mediated blood-brain barrier dysfunction requires non-muscle myosin light chain kinase.","authors":"Richard S Beard, Brian A Hoettels, Jessica M McAllister, Jamie E Meegan, Travis S Wertz, Desiree A Self, Dylan E Hrkach, Daniel Greiner, Kristina Chapman, Nuria Villalba, Xiaoyuan Yang, Byeong J Cha, Cheryl L Jorcyk, Julia T Oxford, Mack H Wu, Sarah Y Yuan","doi":"10.1177/0271678X251318620","DOIUrl":"10.1177/0271678X251318620","url":null,"abstract":"<p><p>Blood-brain barrier (BBB) dysfunction occurs in numerous central nervous system disorders. Unfortunately, a limited understanding of the mechanisms governing barrier function hinders the identification and assessment of BBB-targeted therapies. Previously, we found that non-muscle myosin light chain kinase (nmMLCK) negatively regulates the tight junction protein claudin-5 in brain microvascular endothelial cells (BMVECs) under inflammatory conditions. Here, we used complementary animal and primary cell co-culture models to further investigate nmMLCK and claudin-5 during neuroinflammation. We found that <i>nmMLCK</i>-knockout mice resisted experimental autoimmune encephalomyelitis (EAE), including paralysis, demyelination, neutrophil infiltration, and BBB dysfunction. However, transiently silencing claudin-5 culminated in a fulminant disease course. In parallel, we found that neutrophil-secreted factors triggered a biphasic loss in the barrier quality of wild-type BMVEC monolayers, plus pronounced neutrophil migration during the second phase. Conversely, <i>nmMLCK</i>-knockout monolayers resisted barrier dysfunction and neutrophil migration. Lastly, we found an inverse relationship between claudin-5 expression in BMVECs and neutrophil migration. Overall, our findings support a pathogenic role for nmMLCK in BMVECs during EAE that includes BBB dysfunction and neutrophil infiltration, reveal that claudin-5 contributes to the immune barrier properties of BMVECs, and underscore the harmful effects of claudin-5 loss during neuroinflammation.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1203-1220"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364852","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}
Yoshimichi Sato, Yuya Kato, Atsushi Kanoke, Jennifer Y Sun, Yasuo Nishijima, Ruikang K Wang, Michael Stryker, Hidenori Endo, Jialing Liu
{"title":"Type 2 diabetes abates retrograde collateral flow and promotes leukocyte adhesion following ischemic stroke.","authors":"Yoshimichi Sato, Yuya Kato, Atsushi Kanoke, Jennifer Y Sun, Yasuo Nishijima, Ruikang K Wang, Michael Stryker, Hidenori Endo, Jialing Liu","doi":"10.1177/0271678X251338203","DOIUrl":"10.1177/0271678X251338203","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is associated with impaired leptomeningeal collateral compensation and poor stroke outcome. Neutrophils tethering and rolling on endothelium after stroke can also independently reduce flow velocity. However, the chronology and topological changes in collateral circulation in T2DM is not yet defined. Here, we describe the spatial and temporal blood flow dynamics and vessel diameter changes in pial arteries and veins and leukocyte-endothelial adhesion following middle cerebral artery (MCA) stroke using two-photon microscopy in awake control and T2DM mice. Relative to control mice, T2DM mice already exhibited smaller pial vessels with reduced flow velocity prior to stroke. Following stroke, T2DM mice displayed persistently reduced blood flow in pial arteries and veins, resulting in a poor recovery of downstream penetrating arterial flow and a sustained deficit in microvascular flow. There was also persistent increase of leukocyte adhesion to the endothelium of veins, coincided with elevated neutrophils infiltration into brain parenchyma in T2DM mice compared to control mice after stroke. Our data suggest that T2DM-induced increase in inflammation and chronic remodeling of leptomeningeal vessels may contribute to the observed hemodynamics deficiency after stroke and subsequent poor stroke outcome.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251338203"},"PeriodicalIF":4.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173956","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":"Deciphering the brain glucose metabolism: A gateway to innovative stroke therapies.","authors":"Didier F Pisani, Nicolas Blondeau","doi":"10.1177/0271678X251346277","DOIUrl":"10.1177/0271678X251346277","url":null,"abstract":"<p><p>Stroke is the leading cause of physical disability and death among adults in most Western countries. Consecutive to a vascular occlusion, cells face a brutal reduction in supply of oxygen and glucose and thus an energy failure, which in turn triggers cell death mechanisms. Among brain cells, neurons are the most susceptible to ischemia because of their high metabolic demand and low reservoir of energy substrates. In neurons, glycolysis uses glucose coming from blood or from glycogen stored in astrocytes, underlying the deep astrocyte-neuron metabolic cooperation. During ischemia, both the aerobic and anaerobic pathways and thus energy production are compromised, which disrupts proper cell functioning, notably Na<sup>+</sup>/K<sup>+</sup> ATPase and mitochondria. This results in altered Ca<sup>2+</sup> homeostasis and overproduction of ROS, the latter being further exacerbated during the reperfusion phase. Consequently, glucose metabolism in the different brain cell populations plays a central role in injury and recovery after stroke, and has recently emerged as a promising target for therapeutic intervention. In this context, the overall objective of this article is to review the interconnections between stroke and brain glucose metabolism and to explore how its targeting may offer new therapeutic opportunities in addressing the global stroke epidemic.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251346277"},"PeriodicalIF":4.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173954","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}
Elizabeth G Keeling, Maurizio Bergamino, Lauren R Ott, Molly M McElvogue, Ashley M Stokes
{"title":"Repeatability and reliability of cerebrovascular reactivity in young adults using multi-echo, multi-contrast MRI.","authors":"Elizabeth G Keeling, Maurizio Bergamino, Lauren R Ott, Molly M McElvogue, Ashley M Stokes","doi":"10.1177/0271678X251345292","DOIUrl":"10.1177/0271678X251345292","url":null,"abstract":"<p><p>Cerebrovascular reactivity (CVR) shows promise as a biomarker of vascular integrity and may benefit from a repeatable, reliable, and microvasculature-sensitive acquisition. A combined spin- and gradient-echo (SAGE) functional MRI (fMRI) acquisition may improve repeatability and reliability compared to single spin- (SE) and gradient-echo (GRE) fMRI and provide a microvascular-weighted analysis. The most repeatable and reliable MRI acquisition CVR maps were compared across three CVR paradigms: a breath-hold task, a breath modulation task, and a resting state acquisition. SAGE-fMRI data was acquired in fifteen young adults at two timepoints. Mean gray matter (GM) within-subject coefficient of variation (wCV) and intraclass correlation coefficient (ICC) were compared within the quantitative and weighted SAGE-fMRI CVR maps and single GRE- and SE-fMRI CVR. Total and microvascular MRI inputs with lowest wCV and highest ICC were used to compare three CVR paradigms. Total and microvascular weighted SAGE-fMRI CVR had the lowest wCV and highest ICC across paradigms. The breath-hold paradigm produced significantly higher GM CVR estimates. SAGE repeatably and reliably measures CVR and offers a simultaneous, complementary analysis on total and microvascular scales. The breath-hold paradigm showed significantly higher CVR estimates, but less compliance-dependent protocols may be ideal for applications in patient populations.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251345292"},"PeriodicalIF":4.9,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142453","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}
Myrthe Van Sprengel, Jenna Butterworth, Patrick L Reeson, Craig E Brown
{"title":"Retrograde and anterograde trans-synaptic viral tracing of neuronal connections reveals local and distant effects of ischemic stroke on dendritic spines.","authors":"Myrthe Van Sprengel, Jenna Butterworth, Patrick L Reeson, Craig E Brown","doi":"10.1177/0271678X251345360","DOIUrl":"10.1177/0271678X251345360","url":null,"abstract":"<p><p>Focal stroke leads to complex neurological disturbances with variable recovery. One explanation for this variability is that stroke disrupts local and remote neural circuits via the connectome, termed 'diaschisis'. Past studies have yielded mixed effects of stroke on dendritic structure in distant regions. However, a previous limitation was the lack of sampling specifically from neurons directly connected to those within the infarct. To overcome this, we used retrograde and anterograde trans-synaptic AAVs to examine dendritic spine density in neurons that provide inputs to, or receive outputs (pre- and post-synaptic) from primary forelimb somatosensory cortex at 1 or 6 weeks after stroke. For both pre- and post-synaptic neurons, spine density was generally lower in superficial and deep neurons in peri-infarct and motor cortex at 1 week, which recovered by 6 weeks. By contrast, no changes in spine density were observed in ipsilateral secondary somatosensory (S2) or contralateral primary somatosensory cortex at 1 week, although there was an increase in spines in select S2 neurons at 6 weeks. Our data show that some cortical connections are more disrupted by stroke than others, particularly those in peri-infarct and motor cortex which could serve as an important substrate for stroke recovery and future therapies.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251345360"},"PeriodicalIF":4.9,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142522","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}
Jeffrey B Dennison, Michael C Langham, Andrew S Wiemken, Jing Xu, Richard J Schwab, John A Detre, Felix W Wehrli
{"title":"Concurrent evaluation of cerebral oxygen metabolism and upper airway architecture via temporally resolved MRI.","authors":"Jeffrey B Dennison, Michael C Langham, Andrew S Wiemken, Jing Xu, Richard J Schwab, John A Detre, Felix W Wehrli","doi":"10.1177/0271678X251345293","DOIUrl":"10.1177/0271678X251345293","url":null,"abstract":"<p><p>Obstructive sleep apnea (OSA) disrupts the oxygen supply during apneic and hypopneic events. To evaluate the feasibility of concurrently monitoring cerebral metabolic rate of oxygen (CMRO<sub>2</sub>) and airway anatomy, a magnetic resonance imaging (MRI) pulse sequence was developed that interleaves measurements of CMRO<sub>2</sub> with anatomic imaging of the upper airway at a temporal resolution of 5 seconds. The sequence was first tested in healthy subjects during wakefulness to detect the effect of volitional breath-hold and swallowing apneas on neuro-metabolic parameters and airway morphology. Subsequently, select patients with diagnosed OSA and healthy reference subjects were scanned during 90 minutes of wakefulness and sleep with concurrent electroencephalographic (EEG) monitoring and airway plethysmography. During non-rapid eye movement sleep, changes in metabolic parameters caused by neurovascular-metabolic uncoupling were detected, resulting in sleep-stage dependent reductions in the CMRO<sub>2</sub>. Spontaneous apneas were visible in airway images and confirmed plethysmographically. Recurrent apneas in patients during N1 and N2 sleep led to increased SvO<sub>2</sub> and CBF (hypercapnic-hypoxic response) and decreases in SaO<sub>2</sub> (hypoxemic response from airway closure) resulting in CMRO<sub>2</sub> reductions as large 60%. The results demonstrate the MRI potential of noninvasive assessment of the dynamic changes in airway anatomy and brain metabolism in OSA during sleep.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251345293"},"PeriodicalIF":4.9,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142506","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}