Journal of Cerebral Blood Flow and Metabolism最新文献

{"title":"TSPO deficiency exacerbates acute brain damage after intracerebral hemorrhage in male mice.","authors":"Frederick Bonsack, Rajaneekar Dasari, Ashwin Thomas, Hongyan Xu, Sangeetha Sukumari-Ramesh","doi":"10.1177/0271678X251340509","DOIUrl":"10.1177/0271678X251340509","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is a stroke subtype with no effective treatment despite high morbidity and mortality rates. The delineation of the mechanisms of brain damage after ICH is critical to identifying novel molecular targets for therapeutic intervention. Apart from the augmented expression of 18 kDa translocator protein (TSPO) in microglia/macrophages post-ICH and its potential to track neuroinflammation, the precise function of TSPO after brain damage remains largely enigmatic. In the present study, we employed transgenic animal models, such as global and myeloid-specific conditional knockouts, to elucidate the functional role of TSPO in ICH-induced acute brain damage. Neurological deficits, neurodegeneration, and neuroinflammation were assessed at 3-days post-ICH in male and female mice. Male TSPO global knockout and conditional knockout exhibited enhanced neurobehavioral deficits with a concomitant increase in neurodegeneration and neuroinflammation compared to their respective controls. Interestingly, their female counterparts did not exhibit augmented brain damage compared to the respective controls. Mechanistically, studies employing RNA-Seq and subsequent functional validation demonstrate that TSPO could regulate brain cholesterol efflux, which could partly be responsible for enhanced brain damage in TSPO KO male mice after ICH, warranting further investigation.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251340509"},"PeriodicalIF":4.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078384","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":"Contributions of synaptic glutamate versus neuronal spiking activity to cerebral vascular responses in awake mice.","authors":"Jenna M Peretin, Christopher G Cover, Alberto L Vazquez","doi":"10.1177/0271678X251338407","DOIUrl":"10.1177/0271678X251338407","url":null,"abstract":"<p><p>Neurovascular coupling is the temporal relationship between neuronal activity and regional blood flow changes presumably to meet the high metabolic demands of the brain. Prior fMRI studies have reported excitatory synaptic transmission as more metabolically demanding than neuronal spiking, thus correlating better with cerebral hemodynamics. To investigate this finding with newer optical imaging techniques, we used fluorescent markers for extracellular synaptic glutamate and intracellular neuronal calcium to directly measure relationships between synaptic and spiking activities on local vascular changes in awake mice under evoked and spontaneous conditions. To determine which signal better predicts hemodynamic responses, we used a linear convolution model. Using wide field optical imaging (WFOI), we observed peak fluorescence values of 0.38% and 5.60% in synaptic glutamate and neuronal calcium, respectively, to whisker stimulation, and values of 3.13% and 35.77%, respectively, using two-photon microscopy (2PM). Following whisker stimulation, mean R² values were 0.64 and 0.79 for synaptic glutamate and neuronal calcium, respectively, with WFOI and 0.67 and 0.56, respectively, with 2PM. From WFOI resting-state, mean R² values were 0.73 and 0.68 for synaptic glutamate and neuronal calcium, respectively. Altogether, both signals perform similarly in predicting hemodynamic responses, with no significant differences in their prediction efficacy.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251338407"},"PeriodicalIF":4.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078289","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":"A novel approach for modeling <i>in vivo</i> enzyme turnover in the presence of a suicide inhibitor drug: A proof-of-concept brain PET study on MAG lipase.","authors":"Tommaso Volpi, Daniel Holden, Jean-Dominique Gallezot, Nabeel Nabulsi, Keunpoong Lim, David Labaree, Hong Gao, Michael Kapinos, Edmund J Keliher, Kari R Fonseca, Patrick Trapa, Andrea Varrone, Christer Halldin, Kevin P Maresca, Yiyun Huang, Richard E Carson","doi":"10.1177/0271678X251329254","DOIUrl":"10.1177/0271678X251329254","url":null,"abstract":"<p><p>PET imaging allows the study of enzyme concentration and activity <i>in vivo</i>. The enzyme natural turnover <math><mi>α</mi></math>, relevant for drug development, can be estimated if a suicide inhibitor drug is used. The main aim of this study was to develop a model for estimating <math><mi>α</mi></math> by accounting for the presence of residual inhibitor. We analyzed nonhuman primate PET data with monoacyglycerol lipase (MAGL) tracer [¹¹C]PF-06809247, and suicide inhibitor PF-06818883 (0.03-1.27 mg/kg, active compound PF-06807893). As [¹¹C]PF-06809247 is an irreversible tracer, we used simulations to evaluate the impact of flow limitation on identifiability of kinetic parameters. Based on this, MAGL activity estimates were obtained from three outcome parameters: <i>K</i>_i, <i>k</i>₃, <math><msub><mrow><mover><mrow><mi>K</mi></mrow><mo>˜</mo></mover></mrow><mrow><mn>3</mn></mrow></msub></math> (=<math><mfrac><mrow><msub><mrow><mi>K</mi></mrow><mrow><mn>1</mn></mrow></msub><msub><mrow><mi>K</mi></mrow><mrow><mi>i</mi></mrow></msub></mrow><mrow><msub><mrow><mi>K</mi></mrow><mrow><mn>1</mn></mrow></msub><msub><mrow><mo>-</mo><mi>K</mi></mrow><mrow><mi>i</mi></mrow></msub></mrow></mfrac></math>). A new model, which links enzyme activity to the inhibitor drug's plasma concentration, was used to estimate <math><mi>α</mi></math>. Using a conservative statistical cut-off, MAGL turnover half-lives were estimated (<i>K</i>_i: 3.9 h; <i>k</i>₃: 4.6 h; <math><msub><mrow><mover><mrow><mi>K</mi></mrow><mo>˜</mo></mover></mrow><mrow><mn>3</mn></mrow></msub></math>: 6.1 h) - with faster turnover for <i>K</i>_i (flow-limited). Serial PET experiments and measuring the drug's plasma concentration allowed to estimate <math><mi>α</mi></math> correcting for residual suicide inhibition. This approach can be extended to other PET enzyme targets, improving our understanding of enzyme pathological alterations and suicide inhibitor-based therapies.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251329254"},"PeriodicalIF":4.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078322","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":"Environmental enrichment promotes functional recovery from stroke via enhancing neuroplasticity through the action of <b>β</b>-HB.","authors":"Zhuang-Yin Qu, Chang-Jing Zhang, Ya-Lan Hou, Hui-Lin Li, Long Lin, Ai Teng, Chang-Run Shi, Wen-Shuo Lu, Xiao-Wei Zhang, Fei Li, Lei Chang, Yu-Hui Lin","doi":"10.1177/0271678X251328179","DOIUrl":"10.1177/0271678X251328179","url":null,"abstract":"<p><p>Stroke is a leading cause of adult disability worldwide, unfortunately, no drugs are clinically available to promote functional recovery after stroke. Although animal environmental enrichment is a recognized paradigm for promoting stroke repair, elusive mechanisms hinder its clinical translation. Here, we show that β-hydroxybutyrate (β-HB) level in the peri-infarct cortex is upregulated after environmental enrichment (EE) exposure. Importantly, exogenous supplementation of β-HB promotes functional recovery to a similar extent as EE exposure. Moreover, the beneficial effects of EE on stroke recovery, including functional recovery, neuroplasticity-related proteins upregulation, and structural and functional plasticity enhancement, are abolished by β-HB transporter inhibitor, AR-C155858. Intriguingly, supplementation with (R)-3-hydroxybutyl (R)-β-HB, a ketone ester (KE), substantially increases β-HB level and lessens motor functional impairments. Together, our findings indicate that β-HB is a critical substrate for EE-mediated stroke recovery and supplementation with β-HB monoester drinks may serve as a novel strategy to translate EE from bench to bedside.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251328179"},"PeriodicalIF":4.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078360","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":"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":"<p><p>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.</p>","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}

{"title":"Combination of alpha-1 antitrypsin (A1AT) and anti-TNF<b>α</b> 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":"<p><p>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.</p>","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}

{"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":"<p><p>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; <i>p</i> < 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; <i>p</i> <i><</i> 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; <i>p</i> <i><</i> 0.05). Correlation analyses revealed a significant association between bilirubin levels and blood velocities of MCA (r = -0.9377, <i>p</i> = 0.0002) and ICA (r = 0.8203, <i>p</i> = 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.</p>","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}

{"title":"The brain's \"dark energy\" puzzle <i>upgraded</i>: [¹⁸F]FDG uptake, delivery and phosphorylation, and their coupling with resting-state brain activity.","authors":"Tommaso Volpi, John J Lee, Andrei G Vlassenko, Manu S Goyal, Maurizio Corbetta, Alessandra Bertoldo","doi":"10.1177/0271678X251329707","DOIUrl":"10.1177/0271678X251329707","url":null,"abstract":"<p><p>The brain's resting-state energy consumption is expected to be driven by spontaneous activity. We previously used 50 resting-state fMRI (rs-fMRI) features to predict [¹⁸F]FDG SUVR as a proxy of glucose metabolism. Here, we expanded on our effort by estimating [¹⁸F]FDG kinetic parameters <i>K</i>_i (irreversible uptake), <i>K</i>₁ (delivery), <i>k</i>₃ (phosphorylation) in a large healthy control group (n = 47). Describing the parameters' spatial distribution at high resolution (216 regions), we showed that <i>K</i>₁ is the least redundant (strong posteromedial pattern), and <i>K</i>_i and <i>k</i>₃ have relevant differences (occipital cortices, cerebellum, thalamus). Using multilevel modeling, we investigated how much spatial variance of [¹⁸F]FDG parameters could be explained by a combination of a) rs-fMRI variables, b) cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO₂) from ¹⁵O PET. Rs-fMRI-only models explained part of the individual variance in <i>K</i>_i (35%), <i>K</i>₁ (14%), <i>k</i>₃ (21%), while combining rs-fMRI and CMRO₂ led to satisfactory description of <i>K</i>_i (46%) especially. <i>K</i>_i was sensitive to both local rs-fMRI variables (<i>ReHo</i>) and CMRO₂, <i>k</i>₃ to <i>ReHo</i>, <i>K</i>₁ to CMRO₂. This work represents a comprehensive assessment of the complex underpinnings of brain glucose consumption, and highlights links between 1) glucose phosphorylation and local brain activity, 2) glucose delivery and oxygen consumption.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251329707"},"PeriodicalIF":4.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078380","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":"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":"<p><p>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.</p>","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}

{"title":"Preclinical PET imaging of the developing fetus during pregnancy: Current state and future potential.","authors":"Torben D Pearson, Sarah Bricault, Yu-Shiuan Lin, Katelyn E Barusso, Samhitha Bodangi, Hsiao-Ying Wey","doi":"10.1177/0271678X251340510","DOIUrl":"https://doi.org/10.1177/0271678X251340510","url":null,"abstract":"<p><p>During pregnancy, the fetus is subject to complex interactions of biological and environmental factors that can influence developmental trajectories even into adulthood. Although several factors, such as maternal malnutrition and substance abuse, have been associated with offspring development, the mechanisms through which short- and long-term effects manifest in the fetus are not well understood. To this end, positron emission tomography (PET) imaging using preclinical models has been a promising and underutilized technique for investigating fetal exposure and physiology <i>in utero</i> with minimal invasiveness. Herein, we review the application of PET imaging to fetal medicine and survey the limitations and opportunities for future longitudinal studies of development. Over the past two decades, several studies have utilized preclinical PET in quantitative studies of maternal-fetal exchange dynamics of pharmaceuticals, environmental toxins, or drugs of abuse. Another application has shown [¹⁸F]FDG PET to be a potential biomarker for fetal glucose transport, hypoxia, and brain function <i>in utero</i>. In contrast, only a few studies have employed reversibly binding radioligands to quantify protein markers of dopaminergic signaling and synaptic density in the fetal brain. As PET technology continues to improve, our review highlights a future role for PET in longitudinal studies of fetal health and development.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251340510"},"PeriodicalIF":4.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078338","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}