Journal of Cerebral Blood Flow and Metabolism最新文献

{"title":"Association between PPAR<b>γ</b> polymorphisms and neurological functional disability of ischemic stroke.","authors":"Ran Yan, Xin Qiu, Yalun Dai, Yingyu Jiang, Hongqiu Gu, Yong Jiang, Lingling Ding, Si Cheng, Xia Meng, Yilong Wang, Xingquan Zhao, Hao Li, Yongjun Wang, Zixiao Li","doi":"10.1177/0271678X241274681","DOIUrl":"10.1177/0271678X241274681","url":null,"abstract":"<p><p>Peroxisome proliferator-activated receptor-γ (<i>PPARγ</i>) plays a protective role against brain injury after stroke in mice. However, the relationship between <i>PPARγ</i> gene polymorphisms and the functional outcome of acute ischemic stroke (AIS) remains unknown. 8822 patients from The Third China National Stroke Registry (CNSR-III) after whole-genome sequencing, two functional single nucleotide polymorphisms(SNPs) in <i>PPARγ</i>, rs1801282 C > G and rs3856806 C > T, were further analysed. The primary outcome was neurological functional disability at three months. Of the 8822 patients, 968 (11.0%) and 3497 (39.6%) were carriers of rs1801282 and rs3856806, respectively. Carriers of rs3856806 showed reduced risks for three-month neurological functional disability (OR, 0.84; 95% CI, 0.73-0.98; p = 0.02) and reduced risks for higher infarct volume (OR 0.90, 95% CI, 0.81-0.99, p = 0.04). They also had a reduced risk of neurological functional disability only in case of lower baseline IL-6 levels (OR 0.64, 95% CI 0.48-0.84, P_interaction = 0.01). Carriers of rs1801282 had a reduced risk for three-month neurological functional disability (OR 0.77, 95% CI, 0.61-0.99, p = 0.04). Our study suggested that PPARγ polymorphisms are associated with a reduced risk for neurological functional disability and higher infarct volume in AIS. Therefore, PPARγ can be a potential therapeutic target in AIS.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"328-339"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004338","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":"[¹⁸F]SF51, a novel ¹⁸F-labeled PET radioligand for translocator protein 18kDa (TSPO) in brain, works well in monkeys but fails in humans.","authors":"Xuefeng Yan, Fabrice G Siméon, Jeih-San Liow, Cheryl L Morse, Susovan Jana, Jose A Montero Santamaria, Madeline Jenkins, Sami S Zoghbi, Victor W Pike, Robert B Innis, Paolo Zanotti-Fregonara","doi":"10.1177/0271678X241304924","DOIUrl":"10.1177/0271678X241304924","url":null,"abstract":"<p><p>[¹⁸F]SF51 is a novel radioligand for imaging translocator protein 18 kDa (TSPO) that previously displayed excellent imaging properties in nonhuman primates. This study assessed its performance in human brain and its dosimetry. Seven healthy participants underwent brain PET imaging to measure TSPO binding using a two-tissue compartment model (2TCM) to calculate total distribution volume (<i>V</i>_T). This cohort included two high-affinity binders (HABs), three mixed-affinity binders (MABs), and two low-affinity binders (LABs). Two other participants received whole-body scans to assess radiation exposure. Peak brain radioactivity reached a standardized uptake value (SUV) of 1.4 at 3 minutes post-injection, diminishing to 30% of peak by 120 minutes. The average <i>V</i>_T for all genotype groups was notably low (<1 mL·cm^-3), emphasizing the radioligand's poor binding in brain. [¹⁸F]SF51 remained sensitive to the TSPO polymorphism <i>in vivo</i>, as shown by a two-fold difference in <i>V</i>_T between HABs and LABs. <i>V</i>_T stabilization by 80 minutes post-injection suggested minimal radiometabolite accumulation in brain. The average effective dose was 13.8 ± 0.9 µSv/MBq. Contrary to previously published animal data, [¹⁸F]SF51 showed low binding to human TSPO, with uptake remaining influenced by the rs6971 polymorphism. These findings highlight the challenges of developing TSPO radioligands and underscore the significant species differences that may influence translational outcomes.<b>ClinicalTrials.gov identifier:</b> NCT05564429; registered 10/03/2022.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"365-372"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800308","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":"Respiratory influence on cerebral blood flow and blood volume - A 4D flow MRI study.","authors":"Pontus Söderström, Anders Eklund, Nina Karalija, Britt M Andersson, Katrine Riklund, Lars Bäckman, Jan Malm, Anders Wåhlin","doi":"10.1177/0271678X251316395","DOIUrl":"10.1177/0271678X251316395","url":null,"abstract":"<p><p>Variations in cerebral blood flow and blood volume interact with intracranial pressure and cerebrospinal fluid dynamics, all of which play a crucial role in brain homeostasis. A key physiological modulator is respiration, but its impact on cerebral blood flow and volume has not been thoroughly investigated. Here we used 4D flow MRI in a population-based sample of 65 participants (mean age = 75 ± 1) to quantify these effects. Two gating approaches were considered, one using respiratory-phase and the other using respiratory-time (i.e. raw time in the cycle). For both gating methods, the arterial inflow was significantly larger during exhalation compared to inhalation, whereas the venous outflow was significantly larger during inhalation compared to exhalation. The cerebral blood volume variation per respiratory cycle was 0.83 [0.62, 1.13] ml for respiratory-phase gating and 0.78 [0.59, 1.02] ml for respiratory-time gating. For comparison, the volume variation of the cardiac cycle was 1.01 [0.80, 1.30] ml. Taken together, our results clearly demonstrate respiratory influences on cerebral blood flow. The corresponding vascular volume variations appear to be of the same order of magnitude as those of the cardiac cycle, highlighting respiration as an important modulator of cerebral blood flow and blood volume.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251316395"},"PeriodicalIF":4.9,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065861","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":"Setting standards for brain collection procedures in metabolomic studies.","authors":"Gerald A Dienel, Thaddeus S Nowak","doi":"10.1177/0271678X251314331","DOIUrl":"10.1177/0271678X251314331","url":null,"abstract":"<p><p>Current metabolomics technologies can measure hundreds of chemical entities in tissue extracts with good reliability. However, long-recognized requirements to halt enzyme activities during the initial moments of sample preparation are usually overlooked, allowing marked postmortem shifts in levels of labile metabolites representing diverse pathways. In brain many such changes occur in a matter of seconds. These comments overview the concern, contrast representative studies, and specify approaches to consider as standards in the field going forward. Comparison with established metabolite signatures of in vivo brain is an essential validation step when implementing any collection method.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251314331"},"PeriodicalIF":4.9,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039008","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":"Phosphodiesterase inhibition restores hypoxia-induced cerebrovascular dysfunction subsequent to improved systemic redox homeostasis: A randomized, double-blind, placebo-controlled crossover study.","authors":"Benjamin S Stacey, Christopher J Marley, Hayato Tsukamoto, Tony G Dawkins, Thomas S Owens, Thomas A Calverley, Lewis Fall, Angelo Iannetelli, Ifan Lewis, James M Coulson, Mike Stembridge, Damian M Bailey","doi":"10.1177/0271678X251313747","DOIUrl":"10.1177/0271678X251313747","url":null,"abstract":"<p><p>To what extent sildenafil, a selective inhibitor of the type-5 phosphodiesterase modulates systemic redox status and cerebrovascular function during acute exposure to hypoxia remains unknown. To address this, 12 healthy males (aged 24 ± 3 y) participated in a randomized, placebo-controlled crossover study involving exposure to both normoxia and acute (60 min) hypoxia (Fi<math><msub><mrow><mtext>O</mtext></mrow><mrow><mn>2</mn></mrow></msub></math> = 0.14), followed by oral administration of 50 mg sildenafil and placebo (double-blinded). Venous blood was sampled for the ascorbate radical (A^•-: electron paramagnetic resonance spectroscopy) and nitric oxide metabolites (NO: ozone-based chemiluminescence). Transcranial Doppler ultrasound was employed to determine middle cerebral artery velocity (MCAv), cerebral delivery of oxygen <math><msub><mrow><mtext>(CDO</mtext></mrow><mrow><mn>2</mn></mrow></msub><mtext>),</mtext></math> dynamic cerebral autoregulation (dCA) and cerebrovascular reactivity to hypo/hypercapnia (CVR_{CO2HYPO/HYPER}). Cortical oxyhemoglobin (cO₂Hb) and oxygenation index (OI) were assessed using pulsed continuous wave near infra-red spectroscopy. Hypoxia decreased total plasma NO (<i>P = </i>0.008), <math><msub><mrow><mtext>CDO</mtext></mrow><mrow><mn>2</mn></mrow></msub></math> (<i>P</i> = <0.001) and cO₂Hb (<i>P = </i>0.005). In hypoxia, sildenafil selectively reduced A^•- (<i>P = </i>0.018) and MCA_V (<i>P = </i>0.018), and increased dCA metrics of low-frequency phase (<i>P = </i>0.029) and CVR_CO2HYPER (<i>P = </i>0.007) compared to hypoxia-placebo. Collectively, these findings provide evidence for a PDE-5 inhibitory pathway that enhances select aspects of cerebrovascular function in hypoxia subsequent to a systemic improvement in redox homeostasis and independent of altered vascular NO bioavailability.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251313747"},"PeriodicalIF":4.9,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039004","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":"Task activation results in regional ¹³C-lactate signal increase in the human brain.","authors":"Biranavan Uthayakumar, Nicole Ic Cappelletto, Nadia D Bragagnolo, Albert P Chen, Nathan Ma, William J Perks, Ruby Endre, Fred Tam, Simon J Graham, Chris Heyn, Kayvan R Keshari, Hany Soliman, Charles H Cunningham","doi":"10.1177/0271678X251314683","DOIUrl":"10.1177/0271678X251314683","url":null,"abstract":"<p><p>Hyperpolarized-¹³C magnetic resonance imaging (HP-¹³C MRI) was used to image changes in ¹³C-lactate signal during a visual stimulus condition in comparison to an eyes-closed control condition. Whole-brain ¹³C-pyruvate, ¹³C-lactate and ¹³C-bicarbonate production was imaged in healthy volunteers (N = 6, ages 24-33) for the two conditions using two separate hyperpolarized ¹³C-pyruvate injections. BOLD-fMRI scans were used to delineate regions of functional activation. ¹³C-metabolite signal was normalized by ¹³C-metabolite signal from the brainstem and the percentage change in ¹³C-metabolite signal conditions was calculated. A one-way Wilcoxon signed-rank test showed a significant increase in ¹³C-lactate in regions of activation when compared to the remainder of the brain (<math><mi>p</mi><mo>=</mo><mn>0.02</mn></math>). No significant increase was observed in ¹³C-pyruvate signal (<math><mi>p</mi><mo>=</mo><mn>0.11</mn></math>) or ¹³C-bicarbonate signal (<math><mi>p</mi><mo>=</mo><mn>0.95</mn></math>). The results show an increase in ¹³C-lactate production in activated regions that is measurable with HP-¹³C MRI.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251314683"},"PeriodicalIF":4.9,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038949","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-kinase anchor protein 12 promotes oligodendrogenesis and cognitive recovery in carbon monoxide therapy for traumatic brain injury.","authors":"Yoon Kyung Choi, Takakuni Maki, Anna C Liang, Kazuhide Hayakawa, Seong-Ho Koh, Young-Myeong Kim, Michael J Whalen, Ji Hae Seo, Josephine Lok, Irwin H Gelman, Kyu-Won Kim, Eng H Lo, Ken Arai","doi":"10.1177/0271678X251314371","DOIUrl":"10.1177/0271678X251314371","url":null,"abstract":"<p><p>Therapeutic drug development for central nervous system injuries, such as traumatic brain injury (TBI), presents significant challenges. TBI results in primary mechanical damage followed by secondary injury, leading to cognitive dysfunction and memory loss. Our recent study demonstrated the potential of carbon monoxide-releasing molecules (CORMs) to improve TBI recovery by enhancing neurogenesis. However, a comprehensive TBI recovery strategy requires not only neurogenesis but also oligodendrogenesis. In this study, we elucidate the critical role of A-kinase anchor protein 12 (AKAP12), a scaffolding protein predominantly expressed by intact pericytes, in oligodendrocyte regeneration during CO therapy for TBI. CORM treatment increased AKAP12 expression, which enhanced myelin intensity and mitigated TBI-induced oligodendrocyte loss. In addition, CO promotes the generation of new oligodendrocytes, a process that is impaired by AKAP12 deficiency. Notably, even after TBI, cognitive function was restored in wild-type mice following CORM treatment, but this effect was absent in <i>Akap12</i> knockout mice. These findings highlight the importance of CO-induced AKAP12 upregulation, particularly in pericytes, in supporting oligodendrogenesis and cognitive recovery after TBI. Understanding these mechanisms holds promise for the development of targeted therapies to address TBI-associated impairments.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251314371"},"PeriodicalIF":4.9,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038940","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":"Expression of concern.","authors":"","doi":"10.1177/0271678X251317057","DOIUrl":"10.1177/0271678X251317057","url":null,"abstract":"","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251317057"},"PeriodicalIF":4.9,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028413","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":"Correlation of zero echo time functional MRI with neuronal activity in rats.","authors":"Juha S Valjakka, Jaakko Paasonen, Raimo A Salo, Ekaterina Paasonen, Petteri Stenroos, Irina Gureviciene, Mikko Kettunen, Djaudat Idiyatullin, Heikki Tanila, Shalom Michaeli, Silvia Mangia, Olli Gröhn","doi":"10.1177/0271678X251314682","DOIUrl":"10.1177/0271678X251314682","url":null,"abstract":"<p><p>Zero echo time (zero-TE) pulse sequences provide a quiet and artifact-free alternative to conventional functional magnetic resonance imaging (fMRI) pulse sequences. The fast readouts (<1 ms) utilized in zero-TE fMRI produce an image contrast with negligible contributions from blood oxygenation level-dependent (BOLD) mechanisms, yet the zero-TE contrast is highly sensitive to brain function. However, the precise relationship between the zero-TE contrast and neuronal activity has not been determined. Therefore, we aimed to derive a function to model the temporal dynamics of the zero-TE fMRI signal in response to neuronal activity. Furthermore, we examined the correlation of zero-TE fMRI with neuronal activity across stimulation frequencies. To these ends, we performed simultaneous electrophysiological recordings and zero-TE fMRI in rats subjected to whisker stimulation. The presented impulse response function provides a basis for the statistical modeling of neuronal activity-induced changes in the zero-TE fMRI signal. The temporal characteristics of the zero-TE fMRI response were found to be consistent with the previously postulated non-BOLD hemodynamic origin of the functional contrast. The zero-TE fMRI signal was well predicted by electrophysiological recordings, although systematic stimulation-dependent residuals were also observed, suggesting nonlinearities in neurovascular coupling. We conclude that zero-TE fMRI provides a robust proxy for neuronal activity.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251314682"},"PeriodicalIF":4.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic hypertension and perfusion deficits conjointly affect disease outcome after tPA treatment in a rodent model of thromboembolic stroke.","authors":"Bart Aa Franx, Ivo Acw Tiebosch, Annette van der Toorn, Rick M Dijkhuizen","doi":"10.1177/0271678X241310732","DOIUrl":"10.1177/0271678X241310732","url":null,"abstract":"<p><p>Futile recanalization hampers prognoses for ischemic stroke patients despite successful recanalization therapy. Allegedly, hypertension and reperfusion deficits contribute, but a better understanding is needed of how they interact and mediate disease outcome. We reassessed data from spontaneously hypertensive and normotensive Wistar-Kyoto rats (male, n = 6-7/group) that were subjected to two-hour embolic middle cerebral artery occlusion and thrombolysis in preclinical trials. Serial MRI allowed lesion monitoring and parcellation of regions-of-interest that represented infarcted (core) or recovered (perilesional) tissue. Imaging markers of hemodynamics and blood-brain barrier (BBB) status were related to tissue fate and neurological outcome. Despite comparable ischemic severity during occlusion between groups, hypertensive rats temporarily developed larger lesions after recanalization, with permanently aggravated vasogenic edema and BBB permeability. One day post-stroke, cerebral blood flow (CBF) was variably restored, but blood transit times were consistently prolonged in hypertensives. Compared to the core, perilesional CBF was normo-to-hyperperfused in both groups, yet this pattern reversed after seven days. Volumes of hypo- and hyperperfusion developed irrespective of strain, differentially associating with final infarct volume and behavioral outcome. Incomplete reperfusion and cerebral injury after thrombolysis were augmented in hypertensive rats. One day after thrombolysis, fractional volumes of hypoperfusion associated with worsened outcomes, while fractional volumes of hyperperfusion appeared beneficial or benign.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241310732"},"PeriodicalIF":4.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023554","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}