首页 > 最新文献

Journal of Cerebral Blood Flow and Metabolism最新文献

英文 中文
Dysmaturation of sleep state and electroencephalographic activity after hypoxia-ischaemia in preterm fetal sheep. 早产胎羊缺氧缺血后的睡眠状态和脑电活动失调。
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-01 Epub Date: 2024-02-28 DOI: 10.1177/0271678X241236014
Christopher A Lear, Benjamin A Lear, Joanne O Davidson, Victoria J King, Yoshiki Maeda, Alice McDouall, Simerdeep K Dhillon, Alistair J Gunn, Laura Bennet

Antenatal hypoxia-ischaemia (HI) in preterm fetal sheep can trigger delayed evolution of severe, cystic white matter injury (WMI), in a similar timecourse to WMI in preterm infants. We therefore examined how severe hypoxia-ischaemia affects recovery of electroencephalographic (EEG) activity. Chronically instrumented preterm fetal sheep (0.7 gestation) received 25 min of complete umbilical cord occlusion (UCO, n = 9) or sham occlusion (controls, n = 9), and recovered for 21 days. HI was associated with a shift to lower frequency EEG activity for the first 5 days with persisting loss of EEG power in the delta and theta bands, and initial loss of power in the alpha and beta bands in the first 14 days of recovery. In the final 3 days of recovery, there was a marked rhythmic shift towards higher frequency EEG activity after UCO. The UCO group spent less time in high-voltage sleep, and in the early evening (7:02 pm ± 47 min) abruptly stopped cycling between sleep states, with a shift to a high frequency state for 2 h 48 min ± 40 min, with tonic electromyographic activity. These findings demonstrate persisting EEG and sleep state dysmaturation after severe hypoxia-ischaemia. Loss of fetal or neonatal sleep state cycling in the early evening may be a useful biomarker for evolving cystic WMI.

早产胎羊产前缺氧缺血(HI)可引发严重囊性白质损伤(WMI)的延迟演变,其时间进程与早产儿的WMI相似。因此,我们研究了严重缺氧缺血如何影响脑电图(EEG)活动的恢复。长期接受仪器检测的早产胎羊(0.7 胎龄)接受了 25 分钟的脐带完全闭塞(UCO,n = 9)或假闭塞(对照组,n = 9),并恢复了 21 天。HI 与头 5 天脑电活动向低频转移有关,δ和θ波段的脑电功率持续下降,在恢复的头 14 天,α和β波段的功率开始下降。在恢复的最后 3 天,UCO 后的脑电图活动明显有节奏地转向更高频率。UCO 组在高压睡眠中花费的时间较少,在傍晚(7:02 pm ± 47 min)突然停止了睡眠状态之间的循环,转入高频状态达 2 h 48 min ± 40 min,并伴有强直性肌电活动。这些发现表明,在严重缺氧缺血后,脑电图和睡眠状态持续失调。胎儿或新生儿傍晚睡眠状态循环的丧失可能是囊性 WMI 演变的有用生物标志物。
{"title":"Dysmaturation of sleep state and electroencephalographic activity after hypoxia-ischaemia in preterm fetal sheep.","authors":"Christopher A Lear, Benjamin A Lear, Joanne O Davidson, Victoria J King, Yoshiki Maeda, Alice McDouall, Simerdeep K Dhillon, Alistair J Gunn, Laura Bennet","doi":"10.1177/0271678X241236014","DOIUrl":"10.1177/0271678X241236014","url":null,"abstract":"<p><p>Antenatal hypoxia-ischaemia (HI) in preterm fetal sheep can trigger delayed evolution of severe, cystic white matter injury (WMI), in a similar timecourse to WMI in preterm infants. We therefore examined how severe hypoxia-ischaemia affects recovery of electroencephalographic (EEG) activity. Chronically instrumented preterm fetal sheep (0.7 gestation) received 25 min of complete umbilical cord occlusion (UCO, n = 9) or sham occlusion (controls, n = 9), and recovered for 21 days. HI was associated with a shift to lower frequency EEG activity for the first 5 days with persisting loss of EEG power in the delta and theta bands, and initial loss of power in the alpha and beta bands in the first 14 days of recovery. In the final 3 days of recovery, there was a marked rhythmic shift towards higher frequency EEG activity after UCO. The UCO group spent less time in high-voltage sleep, and in the early evening (7:02 pm ± 47 min) abruptly stopped cycling between sleep states, with a shift to a high frequency state for 2 h 48 min ± 40 min, with tonic electromyographic activity. These findings demonstrate persisting EEG and sleep state dysmaturation after severe hypoxia-ischaemia. Loss of fetal or neonatal sleep state cycling in the early evening may be a useful biomarker for evolving cystic WMI.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1376-1392"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Long-term isoflurane anesthesia induces cognitive deficits via AQP4 depolarization mediated blunted glymphatic inflammatory proteins clearance. 长期异氟醚麻醉通过AQP4去极化介导的甘油炎症蛋白清除障碍诱发认知障碍。
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-01 Epub Date: 2024-03-05 DOI: 10.1177/0271678X241237073
Rui Dong, Yuqiang Han, Pin Lv, Linhao Jiang, Zimo Wang, Liangyu Peng, Shuai Liu, Zhengliang Ma, Tianjiao Xia, Bing Zhang, Xiaoping Gu

Perioperative neurocognitive disorders (PND) refer to cognitive deterioration that occurs after surgery or anesthesia. Prolonged isoflurane exposure has potential neurotoxicity and induces PND, but the mechanism is unclear. The glymphatic system clears harmful metabolic waste from the brain. This study sought to unveil the functions of glymphatic system in PND and explore the underlying molecular mechanisms. The PND mice model was established by long term isoflurane anesthesia. The glymphatic function was assessed by multiple in vitro and in vivo methods. An adeno-associated virus was used to overexpress AQP4 and TGN-020 was used to inhibit its function. This research revealed that the glymphatic system was impaired in PND mice and the blunted glymphatic transport was closely associated with the accumulation of inflammatory proteins in the hippocampus. Increasing AQP4 polarization could enhance glymphatic transport and suppresses neuroinflammation, thereby improve cognitive function in the PND model mice. However, a marked impaired glymphatic inflammatory proteins clearance and the more severe cognitive dysfunction were observed when decreasing AQP4 polarization. Therefore, long-term isoflurane anesthesia causes blunted glymphatic system by inducing AQP4 depolarization, enhanced the AQP4 polarization can alleviate the glymphatic system malfunction and reduce the neuroinflammatory response, which may be a potential treatment strategy for PND.

围手术期神经认知障碍(PND)是指手术或麻醉后出现的认知功能退化。长时间接触异氟醚可能会导致神经中毒并诱发 PND,但其机制尚不清楚。甘油系统能清除大脑中的有害代谢废物。本研究试图揭示甘液系统在 PND 中的功能,并探索其潜在的分子机制。通过长期异氟醚麻醉建立了 PND 小鼠模型。通过多种体外和体内方法对甘泳功能进行了评估。使用腺相关病毒过表达 AQP4,使用 TGN-020 抑制其功能。研究发现,PND 小鼠的甘液系统受损,而甘液转运功能减弱与海马中炎症蛋白的积累密切相关。增加AQP4极化可增强甘液转运,抑制神经炎症,从而改善PND模型小鼠的认知功能。然而,当降低 AQP4 极化程度时,会观察到明显的甘油性炎性蛋白清除障碍和更严重的认知功能障碍。因此,长期异氟醚麻醉通过诱导AQP4去极化而导致甘液系统功能减退,增强AQP4极化可缓解甘液系统功能失调并减轻神经炎症反应,这可能是治疗PND的一种潜在策略。
{"title":"Long-term isoflurane anesthesia induces cognitive deficits via AQP4 depolarization mediated blunted glymphatic inflammatory proteins clearance.","authors":"Rui Dong, Yuqiang Han, Pin Lv, Linhao Jiang, Zimo Wang, Liangyu Peng, Shuai Liu, Zhengliang Ma, Tianjiao Xia, Bing Zhang, Xiaoping Gu","doi":"10.1177/0271678X241237073","DOIUrl":"10.1177/0271678X241237073","url":null,"abstract":"<p><p>Perioperative neurocognitive disorders (PND) refer to cognitive deterioration that occurs after surgery or anesthesia. Prolonged isoflurane exposure has potential neurotoxicity and induces PND, but the mechanism is unclear. The glymphatic system clears harmful metabolic waste from the brain. This study sought to unveil the functions of glymphatic system in PND and explore the underlying molecular mechanisms. The PND mice model was established by long term isoflurane anesthesia. The glymphatic function was assessed by multiple in vitro and in vivo methods. An adeno-associated virus was used to overexpress AQP4 and TGN-020 was used to inhibit its function. This research revealed that the glymphatic system was impaired in PND mice and the blunted glymphatic transport was closely associated with the accumulation of inflammatory proteins in the hippocampus. Increasing AQP4 polarization could enhance glymphatic transport and suppresses neuroinflammation, thereby improve cognitive function in the PND model mice. However, a marked impaired glymphatic inflammatory proteins clearance and the more severe cognitive dysfunction were observed when decreasing AQP4 polarization. Therefore, long-term isoflurane anesthesia causes blunted glymphatic system by inducing AQP4 depolarization, enhanced the AQP4 polarization can alleviate the glymphatic system malfunction and reduce the neuroinflammatory response, which may be a potential treatment strategy for PND.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1450-1466"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Perfusion imaging by arterial spin labeling in migraine: A literature review. 偏头痛的动脉自旋标记灌注成像:文献综述。
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-01 Epub Date: 2024-03-14 DOI: 10.1177/0271678X241237733
Severin Schramm, Corinna Börner, Miriam Reichert, Gabriel Hoffmann, Stephan Kaczmarz, Michael Griessmair, Kirsten Jung, Maria T Berndt, Claus Zimmer, Thomas Baum, Florian Heinen, Michaela V Bonfert, Nico Sollmann

Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging (MRI) method for the assessment of cerebral blood flow (CBF). This review summarizes recent ASL-based investigations in adult and pediatric patients with migraine with aura, migraine without aura, and chronic migraine. A systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted within PubMed and reference sections of articles identified from April 2014 to November 2022. Out of 236 initial articles, 20 remained after filtering, encompassing data from 1155 subjects in total. Cross-sectional studies in adults showed inconsistent results, while longitudinal studies demonstrated that cerebral perfusion changes over the migraine cycle can be tracked using ASL. The most consistent findings were observed in ictal states among pediatric migraine patients, where studies showed hypoperfusion matching aura symptoms during early imaging followed by hyperperfusion. Overall, ASL is a useful but currently underutilized modality for evaluating cerebral perfusion in patients with migraine. The generalizability of results is currently limited by heterogeneities regarding study design and documentation of clinical variables (e.g., relation of attacks to scanning timepoint, migraine subtypes). Future MRI studies should consider augmenting imaging protocols with ASL to further elucidate perfusion dynamics in migraine.

动脉自旋标记(ASL)是一种评估脑血流(CBF)的无创磁共振成像(MRI)方法。本综述总结了近期对先兆偏头痛、无先兆偏头痛和慢性偏头痛的成人和儿童患者进行的基于 ASL 的研究。根据系统综述和元分析首选报告项目(PRISMA)指南,在PubMed和参考文献中对2014年4月至2022年11月期间的文章进行了系统检索。在 236 篇初始文章中,经过筛选后保留了 20 篇,共包含 1155 名受试者的数据。成人横断面研究显示的结果并不一致,而纵向研究则表明,偏头痛周期内的脑灌注变化可通过 ASL 追踪。在小儿偏头痛患者的发作状态下观察到的结果最为一致,研究显示,在早期成像时,脑灌注不足与先兆症状相匹配,随后出现脑灌注亢进。总之,ASL 是评估偏头痛患者脑灌注情况的一种有用但目前未得到充分利用的方法。目前,研究设计和临床变量记录(如发作与扫描时间点的关系、偏头痛亚型)方面的异质性限制了研究结果的推广性。未来的 MRI 研究应考虑使用 ASL 增强成像方案,以进一步阐明偏头痛的灌注动态。
{"title":"Perfusion imaging by arterial spin labeling in migraine: A literature review.","authors":"Severin Schramm, Corinna Börner, Miriam Reichert, Gabriel Hoffmann, Stephan Kaczmarz, Michael Griessmair, Kirsten Jung, Maria T Berndt, Claus Zimmer, Thomas Baum, Florian Heinen, Michaela V Bonfert, Nico Sollmann","doi":"10.1177/0271678X241237733","DOIUrl":"10.1177/0271678X241237733","url":null,"abstract":"<p><p>Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging (MRI) method for the assessment of cerebral blood flow (CBF). This review summarizes recent ASL-based investigations in adult and pediatric patients with migraine with aura, migraine without aura, and chronic migraine. A systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted within PubMed and reference sections of articles identified from April 2014 to November 2022. Out of 236 initial articles, 20 remained after filtering, encompassing data from 1155 subjects in total. Cross-sectional studies in adults showed inconsistent results, while longitudinal studies demonstrated that cerebral perfusion changes over the migraine cycle can be tracked using ASL. The most consistent findings were observed in ictal states among pediatric migraine patients, where studies showed hypoperfusion matching aura symptoms during early imaging followed by hyperperfusion. Overall, ASL is a useful but currently underutilized modality for evaluating cerebral perfusion in patients with migraine. The generalizability of results is currently limited by heterogeneities regarding study design and documentation of clinical variables (e.g., relation of attacks to scanning timepoint, migraine subtypes). Future MRI studies should consider augmenting imaging protocols with ASL to further elucidate perfusion dynamics in migraine.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1253-1270"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pharmacological preclinical comparison of tenecteplase and alteplase for the treatment of acute stroke. 替奈普酶和阿替普酶治疗急性中风的药理临床前比较。
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-01 Epub Date: 2024-03-04 DOI: 10.1177/0271678X241237427
Clara Correa-Paz, María Pérez-Mato, Mathys Bellemain-Sagnard, Marco González-Domínguez, Pauline Marie, Lara Pérez-Gayol, Esteban López-Arias, Lucia Del Pozo-Filíu, Sonia López-Amoedo, Ana Bugallo-Casal, María Luz Alonso-Alonso, María Candamo-Lourido, María Santamaría-Cadavid, Susana Arias-Rivas, Manuel Rodríguez-Yañez, Ramón Iglesias-Rey, José Castillo, Denis Vivien, Marina Rubio, Francisco Campos

Alteplase (rtPA) remains the standard thrombolytic drug for acute ischemic stroke. However, new rtPA-derived molecules, such as tenecteplase (TNK), with prolonged half-lives following a single bolus administration, have been developed. Although TNK is currently under clinical evaluation, the limited preclinical data highlight the need for additional studies to elucidate its benefits. The toxicities of rtPA and TNK were evaluated in endothelial cells, astrocytes, and neuronal cells. In addition, their in vivo efficacy was independently assessed at two research centers using an ischemic thromboembolic mouse model. Both therapies were tested via early (20 and 30 min) and late administration (4 and 4.5 h) after stroke. rtPA, but not TNK, caused cell death only in neuronal cultures. Mice were less sensitive to thrombolytic therapies than humans, requiring doses 10-fold higher than the established clinical dose. A single bolus dose of 2.5 mg/kg TNK led to an infarct reduction similar to perfusion with 10 mg/kg of rtPA. Early administration of TNK decreased the hemorrhagic transformations compared to that by the early administration of rtPA; however, this result was not obtained following late administration. These two independent preclinical studies support the use of TNK as a promising reperfusion alternative to rtPA.

阿替普酶(rtPA)仍然是治疗急性缺血性中风的标准溶栓药物。然而,新的 rtPA 衍生分子(如 tenecteplase (TNK))已经开发出来,其单次给药后半衰期较长。尽管 TNK 目前正在接受临床评估,但有限的临床前数据凸显了进行更多研究以阐明其益处的必要性。在内皮细胞、星形胶质细胞和神经细胞中评估了 rtPA 和 TNK 的毒性。此外,两个研究中心还使用缺血性血栓栓塞小鼠模型对其体内疗效进行了独立评估。两种疗法都在中风后早期(20 分钟和 30 分钟)和晚期(4 小时和 4.5 小时)进行了测试。小鼠对溶栓疗法的敏感性低于人类,所需的剂量是临床既定剂量的 10 倍。单次注射2.5毫克/千克TNK可使梗死面积缩小,与灌注10毫克/千克rtPA的效果相似。与早期注射rtPA相比,早期注射TNK可减少出血转化;但晚期注射TNK则没有这种效果。这两项独立的临床前研究支持使用 TNK 作为 rtPA 的再灌注替代品。
{"title":"Pharmacological preclinical comparison of tenecteplase and alteplase for the treatment of acute stroke.","authors":"Clara Correa-Paz, María Pérez-Mato, Mathys Bellemain-Sagnard, Marco González-Domínguez, Pauline Marie, Lara Pérez-Gayol, Esteban López-Arias, Lucia Del Pozo-Filíu, Sonia López-Amoedo, Ana Bugallo-Casal, María Luz Alonso-Alonso, María Candamo-Lourido, María Santamaría-Cadavid, Susana Arias-Rivas, Manuel Rodríguez-Yañez, Ramón Iglesias-Rey, José Castillo, Denis Vivien, Marina Rubio, Francisco Campos","doi":"10.1177/0271678X241237427","DOIUrl":"10.1177/0271678X241237427","url":null,"abstract":"<p><p>Alteplase (rtPA) remains the standard thrombolytic drug for acute ischemic stroke. However, new rtPA-derived molecules, such as tenecteplase (TNK), with prolonged half-lives following a single <i>bolus</i> administration, have been developed. Although TNK is currently under clinical evaluation, the limited preclinical data highlight the need for additional studies to elucidate its benefits. The toxicities of rtPA and TNK were evaluated in endothelial cells, astrocytes, and neuronal cells. In addition, their <i>in vivo</i> efficacy was independently assessed at two research centers using an ischemic thromboembolic mouse model. Both therapies were tested via early (20 and 30 min) and late administration (4 and 4.5 h) after stroke. rtPA, but not TNK, caused cell death only in neuronal cultures. Mice were less sensitive to thrombolytic therapies than humans, requiring doses 10-fold higher than the established clinical dose. A single <i>bolus</i> dose of 2.5 mg/kg TNK led to an infarct reduction similar to perfusion with 10 mg/kg of rtPA. Early administration of TNK decreased the hemorrhagic transformations compared to that by the early administration of rtPA; however, this result was not obtained following late administration. These two independent preclinical studies support the use of TNK as a promising reperfusion alternative to rtPA.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1306-1318"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of cerebral oxygen extraction fraction using ASE and TRUST methods in patients with sickle cell disease and healthy controls. 使用 ASE 和 TRUST 方法比较镰状细胞病患者和健康对照组的脑氧萃取分数。
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-01 Epub Date: 2024-03-04 DOI: 10.1177/0271678X241237072
Slim Fellah, Chunwei Ying, Yan Wang, Kristin P Guilliams, Melanie E Fields, Yasheng Chen, Josiah Lewis, Amy Mirro, Rachel Cohen, Nkemdilim Igwe, Cihat Eldeniz, Dengrong Jiang, Hanzhang Lu, William J Powers, Jin-Moo Lee, Andria L Ford, Hongyu An

Abnormal oxygen extraction fraction (OEF), a putative biomarker of cerebral metabolic stress, may indicate compromised oxygen delivery and ischemic vulnerability in patients with sickle cell disease (SCD). Elevated OEF was observed at the tissue level across the brain using an asymmetric spin echo (ASE) MR method, while variable global OEFs were found from the superior sagittal sinus (SSS) using a T2-relaxation-under-spin-tagging (TRUST) MRI method with different calibration models. In this study, we aimed to compare the average ASE-OEF in the SSS drainage territory and TRUST-OEF in the SSS from the same SCD patients and healthy controls. 74 participants (SCD: N = 49; controls: N = 25) underwent brain MRI. TRUST-OEF was quantified using the Lu-bovine, Bush-HbA and Li-Bush-HbS models. ASE-OEF and TRUST-OEF were significantly associated in healthy controls after controlling for hematocrit using the Lu-bovine or the Bush-HbA model. However, no association was found between ASE-OEF and TRUST-OEF in patients with SCD using either the Bush-HbA or the Li-Bush-HbS model. Plausible explanations include a discordance between spatially volume-averaged oxygenation brain tissue and flow-weighted volume-averaged oxygenation in SSS or sub-optimal calibration in SCD. Further work is needed to refine and validate non-invasive MR OEF measurements in SCD.

氧萃取分数(OEF)是大脑代谢压力的一种假定生物标志物,它的异常可能表明镰状细胞病(SCD)患者的氧输送受到影响,容易缺血。使用非对称自旋回波(ASE)磁共振方法在整个大脑的组织水平观察到 OEF 升高,而使用不同校准模型的 T2- 松弛-自旋下标记(TRUST)磁共振成像方法从上矢状窦(SSS)发现了不同的全局 OEF。在本研究中,我们旨在比较 SCD 患者和健康对照组 SSS 引流区的平均 ASE-OEF 和 SSS 的 TRUST-OEF。74 名参与者(SCD:49 人;对照组:25 人)接受了脑磁共振成像检查。TRUST-OEF 采用 Lu-bovine、Bush-HbA 和 Li-Bush-HbS 模型进行量化。使用 Lu-bovine 或 Bush-HbA 模型控制血细胞比容后,健康对照组的 ASE-OEF 和 TRUST-OEF 显著相关。但是,在使用 Bush-HbA 或 Li-Bush-HbS 模型的 SCD 患者中,ASE-OEF 和 TRUST-OEF 之间没有关联。可能的解释包括:SSS 中脑组织空间容积平均氧合与血流加权容积平均氧合不一致,或 SCD 中校准不理想。需要进一步开展工作来完善和验证 SCD 中的无创 MR OEF 测量。
{"title":"Comparison of cerebral oxygen extraction fraction using ASE and TRUST methods in patients with sickle cell disease and healthy controls.","authors":"Slim Fellah, Chunwei Ying, Yan Wang, Kristin P Guilliams, Melanie E Fields, Yasheng Chen, Josiah Lewis, Amy Mirro, Rachel Cohen, Nkemdilim Igwe, Cihat Eldeniz, Dengrong Jiang, Hanzhang Lu, William J Powers, Jin-Moo Lee, Andria L Ford, Hongyu An","doi":"10.1177/0271678X241237072","DOIUrl":"10.1177/0271678X241237072","url":null,"abstract":"<p><p>Abnormal oxygen extraction fraction (OEF), a putative biomarker of cerebral metabolic stress, may indicate compromised oxygen delivery and ischemic vulnerability in patients with sickle cell disease (SCD). Elevated OEF was observed at the tissue level across the brain using an asymmetric spin echo (ASE) MR method, while variable global OEFs were found from the superior sagittal sinus (SSS) using a T2-relaxation-under-spin-tagging (TRUST) MRI method with different calibration models. In this study, we aimed to compare the average ASE-OEF in the SSS drainage territory and TRUST-OEF in the SSS from the same SCD patients and healthy controls. 74 participants (SCD: N = 49; controls: N = 25) underwent brain MRI. TRUST-OEF was quantified using the Lu-bovine, Bush-HbA and Li-Bush-HbS models. ASE-OEF and TRUST-OEF were significantly associated in healthy controls after controlling for hematocrit using the Lu-bovine or the Bush-HbA model. However, no association was found between ASE-OEF and TRUST-OEF in patients with SCD using either the Bush-HbA or the Li-Bush-HbS model. Plausible explanations include a discordance between spatially volume-averaged oxygenation brain tissue and flow-weighted volume-averaged oxygenation in SSS or sub-optimal calibration in SCD. Further work is needed to refine and validate non-invasive MR OEF measurements in SCD.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1404-1416"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vascular contributions to cognitive decline: Beyond amyloid and tau in the Harvard Aging Brain Study. 血管对认知能力下降的影响:哈佛大学老龄化大脑研究中的淀粉样蛋白和陶氏蛋白之外的因素。
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-01 Epub Date: 2024-03-07 DOI: 10.1177/0271678X241237624
Zahra Shirzadi, Rory Boyle, Wai-Ying W Yau, Gillian Coughlan, Jessie Fanglu Fu, Michael J Properzi, Rachel F Buckley, Hyun-Sik Yang, Catherine E Scanlon, Stephanie Hsieh, Rebecca E Amariglio, Kathryn Papp, Dorene Rentz, Julie C Price, Keith A Johnson, Reisa A Sperling, Jasmeer P Chhatwal, Aaron P Schultz

In addition to amyloid and tau pathology, elevated systemic vascular risk, white matter injury, and reduced cerebral blood flow contribute to late-life cognitive decline. Given the strong collinearity among these parameters, we proposed a framework to extract the independent latent features underlying cognitive decline using the Harvard Aging Brain Study (N = 166 cognitively unimpaired older adults at baseline). We used the following measures from the baseline visit: cortical amyloid, inferior temporal cortex tau, relative cerebral blood flow, white matter hyperintensities, peak width of skeletonized mean diffusivity, and Framingham Heart Study cardiovascular disease risk. We used exploratory factor analysis to extract orthogonal factors from these variables and their interactions. These factors were used in a regression model to explain longitudinal Preclinical Alzheimer Cognitive Composite-5 (PACC) decline (follow-up = 8.5 ±2.7 years). We next examined whether gray matter volume atrophy acts as a mediator of factors and PACC decline. Latent factors of systemic vascular risk, white matter injury, and relative cerebral blood flow independently explain cognitive decline beyond amyloid and tau. Gray matter volume atrophy mediates these associations with the strongest effect on white matter injury. These results suggest that systemic vascular risk contributes to cognitive decline beyond current markers of cerebrovascular injury, amyloid, and tau.

除了淀粉样蛋白和 tau 病理学之外,全身血管风险升高、白质损伤和脑血流量减少也是导致晚年认知能力下降的原因。鉴于这些参数之间存在很强的共线性,我们提出了一个框架,利用哈佛大学老年脑研究(N = 166 名基线认知功能未受损的老年人)来提取认知功能衰退的独立潜在特征。我们使用了基线访问中的以下测量指标:皮层淀粉样蛋白、下颞皮层 tau、相对脑血流量、白质高密度、骨架化平均扩散峰值宽度和弗雷明汉心脏研究心血管疾病风险。我们使用探索性因子分析从这些变量及其交互作用中提取正交因子。这些因素被用于回归模型,以解释临床前阿尔茨海默氏症认知综合征-5(PACC)的纵向衰退(随访时间 = 8.5 ± 2.7 年)。接下来,我们研究了灰质体积萎缩是否是各种因素与 PACC 下降之间的中介。除淀粉样蛋白和tau外,全身血管风险、白质损伤和相对脑血流量等潜在因素也能独立解释认知能力的下降。灰质体积萎缩介导了这些关联,对白质损伤的影响最大。这些结果表明,除了目前的脑血管损伤、淀粉样蛋白和 tau 标记之外,系统性血管风险也是认知能力下降的原因之一。
{"title":"Vascular contributions to cognitive decline: Beyond amyloid and tau in the Harvard Aging Brain Study.","authors":"Zahra Shirzadi, Rory Boyle, Wai-Ying W Yau, Gillian Coughlan, Jessie Fanglu Fu, Michael J Properzi, Rachel F Buckley, Hyun-Sik Yang, Catherine E Scanlon, Stephanie Hsieh, Rebecca E Amariglio, Kathryn Papp, Dorene Rentz, Julie C Price, Keith A Johnson, Reisa A Sperling, Jasmeer P Chhatwal, Aaron P Schultz","doi":"10.1177/0271678X241237624","DOIUrl":"10.1177/0271678X241237624","url":null,"abstract":"<p><p>In addition to amyloid and tau pathology, elevated systemic vascular risk, white matter injury, and reduced cerebral blood flow contribute to late-life cognitive decline. Given the strong collinearity among these parameters, we proposed a framework to extract the independent latent features underlying cognitive decline using the Harvard Aging Brain Study (N = 166 cognitively unimpaired older adults at baseline). We used the following measures from the baseline visit: cortical amyloid, inferior temporal cortex tau, relative cerebral blood flow, white matter hyperintensities, peak width of skeletonized mean diffusivity, and Framingham Heart Study cardiovascular disease risk. We used exploratory factor analysis to extract orthogonal factors from these variables and their interactions. These factors were used in a regression model to explain longitudinal Preclinical Alzheimer Cognitive Composite-5 (PACC) decline (follow-up = 8.5 ±2.7 years). We next examined whether gray matter volume atrophy acts as a mediator of factors and PACC decline. Latent factors of systemic vascular risk, white matter injury, and relative cerebral blood flow independently explain cognitive decline beyond amyloid and tau. Gray matter volume atrophy mediates these associations with the strongest effect on white matter injury. These results suggest that systemic vascular risk contributes to cognitive decline beyond current markers of cerebrovascular injury, amyloid, and tau.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1319-1328"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140059482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reduced oxygen extraction fraction in deep cerebral veins associated with cognitive impairment in multiple sclerosis. 多发性硬化症患者脑深部静脉氧气萃取率降低与认知障碍有关。
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-01 Epub Date: 2024-05-31 DOI: 10.1177/0271678X241259551
Hasan Sawan, Chenyang Li, Sagar Buch, Evanthia Bernitsas, E Mark Haacke, Yulin Ge, Yongsheng Chen

Studying the relationship between cerebral oxygen utilization and cognitive impairment is essential to understanding neuronal functional changes in the disease progression of multiple sclerosis (MS). This study explores the potential of using venous susceptibility in internal cerebral veins (ICVs) as an imaging biomarker for cognitive impairment in relapsing-remitting MS (RRMS) patients. Quantitative susceptibility mapping derived from fully flow-compensated MRI phase data was employed to directly measure venous blood oxygen saturation levels (SvO2) in the ICVs. Results revealed a significant reduction in the susceptibility of ICVs (212.4 ± 30.8 ppb vs 239.4 ± 25.9 ppb) and a significant increase of SvO2 (74.5 ± 1.89% vs 72.4 ± 2.23%) in patients with RRMS compared with age- and sex-matched healthy controls. Both the susceptibility of ICVs (r = 0.508, p = 0.031) and the SvO2 (r = -0.498, p = 0.036) exhibited a moderate correlation with cognitive decline in these patients assessed by the Paced Auditory Serial Addition Test, while no significant correlation was observed with clinical disability measured by the Expanded Disability Status Scale. The findings suggest that venous susceptibility in ICVs has the potential to serve as a specific indicator of oxygen metabolism and cognitive function in RRMS. .

研究脑氧利用率与认知障碍之间的关系对于了解多发性硬化症(MS)疾病进展过程中神经元的功能变化至关重要。本研究探讨了利用大脑内静脉(ICV)的静脉易感性作为复发缓解型多发性硬化症(RRMS)患者认知障碍的成像生物标志物的潜力。利用完全血流补偿磁共振成像相位数据得出的定量易感性图谱直接测量了ICV中静脉血氧饱和度(SvO2)水平。结果显示,与年龄和性别匹配的健康对照组相比,RRMS 患者 ICV 的易感性明显降低(212.4 ± 30.8 ppb vs 239.4 ± 25.9 ppb),SvO2 明显升高(74.5 ± 1.89% vs 72.4 ± 2.23%)。ICV 的易感性(r = 0.508,p = 0.031)和 SvO2(r = -0.498,p = 0.036)与步调听觉连续加法测试(Paced Auditory Serial Addition Test)评估的这些患者的认知能力下降呈中度相关,而与扩展残疾状况量表(Expanded Disability Status Scale)测量的临床残疾无明显相关。研究结果表明,ICV 中的静脉易感性有可能成为 RRMS 患者氧代谢和认知功能的特定指标。.
{"title":"Reduced oxygen extraction fraction in deep cerebral veins associated with cognitive impairment in multiple sclerosis.","authors":"Hasan Sawan, Chenyang Li, Sagar Buch, Evanthia Bernitsas, E Mark Haacke, Yulin Ge, Yongsheng Chen","doi":"10.1177/0271678X241259551","DOIUrl":"10.1177/0271678X241259551","url":null,"abstract":"<p><p>Studying the relationship between cerebral oxygen utilization and cognitive impairment is essential to understanding neuronal functional changes in the disease progression of multiple sclerosis (MS). This study explores the potential of using venous susceptibility in internal cerebral veins (ICVs) as an imaging biomarker for cognitive impairment in relapsing-remitting MS (RRMS) patients. Quantitative susceptibility mapping derived from fully flow-compensated MRI phase data was employed to directly measure venous blood oxygen saturation levels (S<sub>v</sub>O<sub>2</sub>) in the ICVs. Results revealed a significant reduction in the susceptibility of ICVs (212.4 ± 30.8 ppb vs 239.4 ± 25.9 ppb) and a significant increase of S<sub>v</sub>O<sub>2</sub> (74.5 ± 1.89% vs 72.4 ± 2.23%) in patients with RRMS compared with age- and sex-matched healthy controls. Both the susceptibility of ICVs (<i>r = </i>0.508, <i>p = </i>0.031) and the S<sub>v</sub>O<sub>2</sub> (<i>r</i> = -0.498, <i>p = </i>0.036) exhibited a moderate correlation with cognitive decline in these patients assessed by the Paced Auditory Serial Addition Test, while no significant correlation was observed with clinical disability measured by the Expanded Disability Status Scale. The findings suggest that venous susceptibility in ICVs has the potential to serve as a specific indicator of oxygen metabolism and cognitive function in RRMS. .</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1298-1305"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults - A 4D flow MRI study. 脑动脉僵化与老年人白质高密度和血管周围间隙有关--4D 流磁共振成像研究。
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-01 Epub Date: 2024-02-05 DOI: 10.1177/0271678X241230741
Cecilia Björnfot, Anders Eklund, Jenny Larsson, William Hansson, Johan Birnefeld, Anders Garpebring, Sara Qvarlander, Lars-Owe D Koskinen, Jan Malm, Anders Wåhlin

White matter hyperintensities (WMH), perivascular spaces (PVS) and lacunes are common MRI features of small vessel disease (SVD). However, no shared underlying pathological mechanism has been identified. We investigated whether SVD burden, in terms of WMH, PVS and lacune status, was related to changes in the cerebral arterial wall by applying global cerebral pulse wave velocity (gcPWV) measurements, a newly described marker of cerebral vascular stiffness. In a population-based cohort of 190 individuals, 66-85 years old, SVD features were estimated from T1-weighted and FLAIR images while gcPWV was estimated from 4D flow MRI data. Additionally, the gcPWV's stability to variations in field-of-view was analyzed. The gcPWV was 10.82 (3.94) m/s and displayed a significant correlation to WMH and white matter PVS volume (r = 0.29, p < 0.001; r = 0.21, p = 0.004 respectively from nonparametric tests) that persisted after adjusting for age, blood pressure variables, body mass index, ApoB/A1 ratio, smoking as well as cerebral pulsatility index, a previously suggested early marker of SVD. The gcPWV displayed satisfactory stability to field-of-view variations. Our results suggest that SVD is accompanied by changes in the cerebral arterial wall that can be captured by considering the velocity of the pulse wave transmission through the cerebral arterial network.

白质高密度(WMH)、血管周围间隙(PVS)和裂隙是小血管病(SVD)常见的磁共振成像特征。然而,目前尚未发现共同的潜在病理机制。我们通过测量全局脑脉搏波速度(gcPWV)(一种新描述的脑血管僵硬度标记),研究了小血管病变的负荷(WMH、PVS和裂隙状态)是否与脑动脉壁的变化有关。在一个由 190 名 66-85 岁的人群组成的队列中,SVD 特征是通过 T1 加权和 FLAIR 图像估算的,而 gcPWV 则是通过四维血流 MRI 数据估算的。此外,还分析了 gcPWV 对视场变化的稳定性。gcPWV 为 10.82 (3.94) m/s,与 WMH 和白质 PVS 体积有显著相关性(r = 0.29,p<0.05)。
{"title":"Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults - A 4D flow MRI study.","authors":"Cecilia Björnfot, Anders Eklund, Jenny Larsson, William Hansson, Johan Birnefeld, Anders Garpebring, Sara Qvarlander, Lars-Owe D Koskinen, Jan Malm, Anders Wåhlin","doi":"10.1177/0271678X241230741","DOIUrl":"10.1177/0271678X241230741","url":null,"abstract":"<p><p>White matter hyperintensities (WMH), perivascular spaces (PVS) and lacunes are common MRI features of small vessel disease (SVD). However, no shared underlying pathological mechanism has been identified. We investigated whether SVD burden, in terms of WMH, PVS and lacune status, was related to changes in the cerebral arterial wall by applying global cerebral pulse wave velocity (gcPWV) measurements, a newly described marker of cerebral vascular stiffness. In a population-based cohort of 190 individuals, 66-85 years old, SVD features were estimated from T1-weighted and FLAIR images while gcPWV was estimated from 4D flow MRI data. Additionally, the gcPWV's stability to variations in field-of-view was analyzed. The gcPWV was 10.82 (3.94) m/s and displayed a significant correlation to WMH and white matter PVS volume (r = 0.29, p < 0.001; r = 0.21, p = 0.004 respectively from nonparametric tests) that persisted after adjusting for age, blood pressure variables, body mass index, ApoB/A1 ratio, smoking as well as cerebral pulsatility index, a previously suggested early marker of SVD. The gcPWV displayed satisfactory stability to field-of-view variations. Our results suggest that SVD is accompanied by changes in the cerebral arterial wall that can be captured by considering the velocity of the pulse wave transmission through the cerebral arterial network.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1343-1351"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lower GLUT1 and unchanged MCT1 in Alzheimer's disease cerebrovasculature. 阿尔茨海默氏症脑血管中的 GLUT1 降低,MCT1 不变。
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-01 Epub Date: 2024-03-05 DOI: 10.1177/0271678X241237484
Manon Leclerc, Cyntia Tremblay, Philippe Bourassa, Julie A Schneider, David A Bennett, Frédéric Calon

The brain is a highly demanding organ, utilizing mainly glucose but also ketone bodies as sources of energy. Glucose transporter-1 (GLUT1) and monocarboxylates transporter-1 (MCT1) respectively transport glucose and ketone bodies across the blood-brain barrier. While reduced glucose uptake by the brain is one of the earliest signs of Alzheimer's disease (AD), no change in the uptake of ketone bodies has been evidenced yet. To probe for changes in GLUT1 and MCT1, we performed Western immunoblotting in microvessel extracts from the parietal cortex of 60 participants of the Religious Orders Study. Participants clinically diagnosed with AD had lower cerebrovascular levels of GLUT1, whereas MCT1 remained unchanged. GLUT1 reduction was associated with lower cognitive scores. No such association was found for MCT1. GLUT1 was inversely correlated with neuritic plaques and cerebrovascular β-secretase-derived fragment levels. No other significant associations were found between both transporters, markers of Aβ and tau pathologies, sex, age at death or apolipoprotein-ε4 genotype. These results suggest that, while a deficit of GLUT1 may underlie the reduced transport of glucose to the brain in AD, no such impairment occurs for MCT1. This study thus supports the exploration of ketone bodies as an alternative energy source for the aging brain.

大脑是一个需要大量能量的器官,主要利用葡萄糖,但也利用酮体作为能量来源。葡萄糖转运体-1(GLUT1)和单羧酸盐转运体-1(MCT1)分别通过血脑屏障转运葡萄糖和酮体。大脑对葡萄糖的吸收减少是阿尔茨海默病(AD)最早出现的症状之一,但目前还没有证据表明酮体的吸收发生了变化。为了探究 GLUT1 和 MCT1 的变化,我们对 60 名宗教团体研究参与者顶叶皮层的微血管提取物进行了 Western 免疫印迹分析。临床诊断为AD的参与者脑血管中的GLUT1水平较低,而MCT1则保持不变。GLUT1 的降低与认知评分的降低有关。而 MCT1 则没有发现这种关联。GLUT1与神经斑块和脑血管β-分泌酶衍生片段水平成反比。在这两种转运体、Aβ和tau病理标记物、性别、死亡年龄或载脂蛋白-ε4基因型之间没有发现其他重要关联。这些结果表明,虽然GLUT1的缺失可能是导致AD患者大脑葡萄糖转运减少的原因,但MCT1却没有出现这种障碍。因此,这项研究支持探索将酮体作为衰老大脑的替代能源。
{"title":"Lower GLUT1 and unchanged MCT1 in Alzheimer's disease cerebrovasculature.","authors":"Manon Leclerc, Cyntia Tremblay, Philippe Bourassa, Julie A Schneider, David A Bennett, Frédéric Calon","doi":"10.1177/0271678X241237484","DOIUrl":"10.1177/0271678X241237484","url":null,"abstract":"<p><p>The brain is a highly demanding organ, utilizing mainly glucose but also ketone bodies as sources of energy. Glucose transporter-1 (GLUT1) and monocarboxylates transporter-1 (MCT1) respectively transport glucose and ketone bodies across the blood-brain barrier. While reduced glucose uptake by the brain is one of the earliest signs of Alzheimer's disease (AD), no change in the uptake of ketone bodies has been evidenced yet. To probe for changes in GLUT1 and MCT1, we performed Western immunoblotting in microvessel extracts from the parietal cortex of 60 participants of the Religious Orders Study. Participants clinically diagnosed with AD had lower cerebrovascular levels of GLUT1, whereas MCT1 remained unchanged. GLUT1 reduction was associated with lower cognitive scores. No such association was found for MCT1. GLUT1 was inversely correlated with neuritic plaques and cerebrovascular β-secretase-derived fragment levels. No other significant associations were found between both transporters, markers of Aβ and tau pathologies, sex, age at death or apolipoprotein-ε4 genotype. These results suggest that, while a deficit of GLUT1 may underlie the reduced transport of glucose to the brain in AD, no such impairment occurs for MCT1. This study thus supports the exploration of ketone bodies as an alternative energy source for the aging brain.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1417-1432"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140028187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The brain's "dark energy" puzzle: How strongly is glucose metabolism linked to resting-state brain activity? 大脑的 "暗能量 "之谜:葡萄糖代谢与静息状态大脑活动的联系有多强?
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-01 Epub Date: 2024-03-05 DOI: 10.1177/0271678X241237974
Tommaso Volpi, Erica Silvestri, Marco Aiello, John J Lee, Andrei G Vlassenko, Manu S Goyal, Maurizio Corbetta, Alessandra Bertoldo

Brain glucose metabolism, which can be investigated at the macroscale level with [18F]FDG PET, displays significant regional variability for reasons that remain unclear. Some of the functional drivers behind this heterogeneity may be captured by resting-state functional magnetic resonance imaging (rs-fMRI). However, the full extent to which an fMRI-based description of the brain's spontaneous activity can describe local metabolism is unknown. Here, using two multimodal datasets of healthy participants, we built a multivariable multilevel model of functional-metabolic associations, assessing multiple functional features, describing the 1) rs-fMRI signal, 2) hemodynamic response, 3) static and 4) time-varying functional connectivity, as predictors of the human brain's metabolic architecture. The full model was trained on one dataset and tested on the other to assess its reproducibility. We found that functional-metabolic spatial coupling is nonlinear and heterogeneous across the brain, and that local measures of rs-fMRI activity and synchrony are more tightly coupled to local metabolism. In the testing dataset, the degree of functional-metabolic spatial coupling was also related to peripheral metabolism. Overall, although a significant proportion of regional metabolic variability can be described by measures of spontaneous activity, additional efforts are needed to explain the remaining variance in the brain's 'dark energy'.

脑糖代谢可通过[18F]FDG PET进行宏观研究,但其区域变异性很大,原因尚不清楚。静息态功能磁共振成像(rs-fMRI)可以捕捉到这种异质性背后的一些功能驱动因素。然而,基于 fMRI 的大脑自发活动描述能在多大程度上描述局部新陈代谢还不得而知。在这里,我们利用两个健康参与者的多模态数据集,建立了一个功能-代谢关联的多变量多层次模型,评估了多种功能特征,描述了 1)rs-fMRI 信号、2)血液动力学响应、3)静态和 4)时变功能连接,作为人脑代谢结构的预测因子。完整模型在一个数据集上进行了训练,并在另一个数据集上进行了测试,以评估其可重复性。我们发现,整个大脑的功能-代谢空间耦合是非线性和异质性的,rs-fMRI 活动和同步的局部测量与局部代谢的耦合更为紧密。在测试数据集中,功能-代谢空间耦合的程度也与外周代谢有关。总之,尽管自发活动的测量方法可以描述相当一部分区域代谢变异,但要解释大脑 "暗能量 "的其余变异还需要更多努力。
{"title":"The brain's \"dark energy\" puzzle: How strongly is glucose metabolism linked to resting-state brain activity?","authors":"Tommaso Volpi, Erica Silvestri, Marco Aiello, John J Lee, Andrei G Vlassenko, Manu S Goyal, Maurizio Corbetta, Alessandra Bertoldo","doi":"10.1177/0271678X241237974","DOIUrl":"10.1177/0271678X241237974","url":null,"abstract":"<p><p>Brain glucose metabolism, which can be investigated at the macroscale level with [<sup>18</sup>F]FDG PET, displays significant regional variability for reasons that remain unclear. Some of the functional drivers behind this heterogeneity may be captured by resting-state functional magnetic resonance imaging (rs-fMRI). However, the full extent to which an fMRI-based description of the brain's spontaneous activity can describe local metabolism is unknown. Here, using two multimodal datasets of healthy participants, we built a multivariable multilevel model of functional-metabolic associations, assessing multiple functional features, describing the 1) rs-fMRI signal, 2) hemodynamic response, 3) static and 4) time-varying functional connectivity, as predictors of the human brain's metabolic architecture. The full model was trained on one dataset and tested on the other to assess its reproducibility. We found that functional-metabolic spatial coupling is nonlinear and heterogeneous across the brain, and that local measures of rs-fMRI activity and synchrony are more tightly coupled to local metabolism. In the testing dataset, the degree of functional-metabolic spatial coupling was also related to peripheral metabolism. Overall, although a significant proportion of regional metabolic variability can be described by measures of spontaneous activity, additional efforts are needed to explain the remaining variance in the brain's 'dark energy'.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1433-1449"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of Cerebral Blood Flow and Metabolism
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1