Journal of Cerebral Blood Flow and Metabolism最新文献_第3页

Combination of alpha-1 antitrypsin (A1AT) and anti-TNFα as a neuroprotective strategy in the early stages after ischemic stroke. α -1抗胰蛋白酶（A1AT）联合抗tnf α作为缺血性脑卒中早期的神经保护策略

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-10-01 Epub Date: 2025-05-15 DOI: 10.1177/0271678X251340234

Paula García-Rodríguez, Laura Ramiro, Alba Simats, Feifei Ma, Anna Rosell, Joan Montaner

{"title":"Combination of alpha-1 antitrypsin (A1AT) and anti-TNFα 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":"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.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1993-2003"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","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}

引用次数: 0

Neuronal deterioration associated with hyperexcitability under mild chronic cerebral hypoperfusion. 轻度慢性脑灌注不足下神经元退化与高兴奋性相关。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-10-01 Epub Date: 2025-05-15 DOI: 10.1177/0271678X251328971

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

{"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":"10.1177/0271678X251328971","url":null,"abstract":"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.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1932-1946"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511680/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retrograde and anterograde trans-synaptic viral tracing of neuronal connections reveals local and distant effects of ischemic stroke on dendritic spines. 神经元连接的逆行和顺行跨突触病毒追踪揭示了局部和远处缺血性中风对树突棘的影响。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-10-01 Epub Date: 2025-05-25 DOI: 10.1177/0271678X251345360

Myrthe Van Sprengel, Jenna Butterworth, Patrick L Reeson, Craig E Brown

{"title":"Retrograde and anterograde trans-synaptic viral tracing of neuronal connections reveals local and distant effects of ischemic stroke on dendritic spines.","authors":"Myrthe Van Sprengel, Jenna Butterworth, Patrick L Reeson, Craig E Brown","doi":"10.1177/0271678X251345360","DOIUrl":"10.1177/0271678X251345360","url":null,"abstract":"Focal stroke leads to complex neurological disturbances with variable recovery. One explanation for this variability is that stroke disrupts local and remote neural circuits via the connectome, termed 'diaschisis'. Past studies have yielded mixed effects of stroke on dendritic structure in distant regions. However, a previous limitation was the lack of sampling specifically from neurons directly connected to those within the infarct. To overcome this, we used retrograde and anterograde trans-synaptic AAVs to examine dendritic spine density in neurons that provide inputs to, or receive outputs (pre- and post-synaptic) from primary forelimb somatosensory cortex at 1 or 6 weeks after stroke. For both pre- and post-synaptic neurons, spine density was generally lower in superficial and deep neurons in peri-infarct and motor cortex at 1 week, which recovered by 6 weeks. By contrast, no changes in spine density were observed in ipsilateral secondary somatosensory (S2) or contralateral primary somatosensory cortex at 1 week, although there was an increase in spines in select S2 neurons at 6 weeks. Our data show that some cortical connections are more disrupted by stroke than others, particularly those in peri-infarct and motor cortex which could serve as an important substrate for stroke recovery and future therapies.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1891-1904"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Concurrent evaluation of cerebral oxygen metabolism and upper airway architecture via temporally resolved MRI. 通过时间分辨MRI同时评估脑氧代谢和上呼吸道结构。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-10-01 Epub Date: 2025-05-25 DOI: 10.1177/0271678X251345293

Jeffrey B Dennison, Michael C Langham, Andrew S Wiemken, Jing Xu, Richard J Schwab, John A Detre, Felix W Wehrli

{"title":"Concurrent evaluation of cerebral oxygen metabolism and upper airway architecture via temporally resolved MRI.","authors":"Jeffrey B Dennison, Michael C Langham, Andrew S Wiemken, Jing Xu, Richard J Schwab, John A Detre, Felix W Wehrli","doi":"10.1177/0271678X251345293","DOIUrl":"10.1177/0271678X251345293","url":null,"abstract":"Obstructive sleep apnea (OSA) disrupts the oxygen supply during apneic and hypopneic events. To evaluate the feasibility of concurrently monitoring cerebral metabolic rate of oxygen (CMRO2) and airway anatomy, a magnetic resonance imaging (MRI) pulse sequence was developed that interleaves measurements of CMRO2 with anatomic imaging of the upper airway at a temporal resolution of 5 seconds. The sequence was first tested in healthy subjects during wakefulness to detect the effect of volitional breath-hold and swallowing apneas on neuro-metabolic parameters and airway morphology. Subsequently, select patients with diagnosed OSA and healthy reference subjects were scanned during 90 minutes of wakefulness and sleep with concurrent electroencephalographic (EEG) monitoring and airway plethysmography. During non-rapid eye movement sleep, changes in metabolic parameters caused by neurovascular-metabolic uncoupling were detected, resulting in sleep-stage dependent reductions in the CMRO2. Spontaneous apneas were visible in airway images and confirmed plethysmographically. Recurrent apneas in patients during N1 and N2 sleep led to increased SvO2 and CBF (hypercapnic-hypoxic response) and decreases in SaO2 (hypoxemic response from airway closure) resulting in CMRO2 reductions as large 60%. The results demonstrate the MRI potential of noninvasive assessment of the dynamic changes in airway anatomy and brain metabolism in OSA during sleep.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"2047-2059"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Amyloid beta peptides inhibit glucose transport at the blood-brain barrier by disrupting the insulin-AKT pathway. 淀粉样肽通过破坏胰岛素- akt通路抑制葡萄糖在血脑屏障的转运。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-10-01 Epub Date: 2025-05-15 DOI: 10.1177/0271678X251332493

Lushan Wang, Geoffry L Curran, Rui Zhong, Zheng Xue, Vaishnavi Veerareddy, Josslen Thieschafer, Paul H Min, Ling Li, Val J Lowe, Karunya K Kandimalla

{"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":"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.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1961-1979"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","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}

引用次数: 0

TSPO deficiency exacerbates acute brain damage after intracerebral hemorrhage in male mice. TSPO缺乏可加重雄性小鼠脑出血后的急性脑损伤。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-09-01 Epub Date: 2025-05-15 DOI: 10.1177/0271678X251340509

Frederick Bonsack, Rajaneekar Dasari, Ashwin Thomas, Hongyan Xu, Sangeetha Sukumari-Ramesh

{"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":"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.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1816-1830"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","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}

引用次数: 0

Contributions of synaptic glutamate versus neuronal spiking activity to cerebral vascular responses in awake mice. 突触谷氨酸和神经元尖峰活动对清醒小鼠脑血管反应的贡献。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-09-01 Epub Date: 2025-05-15 DOI: 10.1177/0271678X251338407

Jenna M Peretin, Christopher G Cover, Alberto L Vazquez

{"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":"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.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1670-1683"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","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}

引用次数: 0

Preclinical PET imaging of the developing fetus during pregnancy: Current state and future potential. 妊娠期胎儿发育的临床前PET显像：现状和未来潜力。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-09-01 Epub Date: 2025-05-14 DOI: 10.1177/0271678X251340510

Torben D Pearson, Sarah Bricault, Yu-Shiuan Lin, Katelyn E Barusso, Samhitha Bodangi, Hsiao-Ying Wey

{"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":"10.1177/0271678X251340510","url":null,"abstract":"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 in utero 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 in utero. 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.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1623-1634"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","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}

引用次数: 0

Deletion of microsomal epoxide hydrolase gene leads to increased density in cerebral vasculature and enhances cerebral blood flow in mice. 小鼠微粒体环氧化物水解酶基因缺失导致脑血管密度增加，脑血流增强。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-09-01 Epub Date: 2025-04-12 DOI: 10.1177/0271678X251333234

Anne Marowsky, Matthias T Wyss, Diana Kindler, Noor-Ul-Ain Khalid, Markus Rudin, Bruno Weber, Michael Arand

{"title":"Deletion of microsomal epoxide hydrolase gene leads to increased density in cerebral vasculature and enhances cerebral blood flow in mice.","authors":"Anne Marowsky, Matthias T Wyss, Diana Kindler, Noor-Ul-Ain Khalid, Markus Rudin, Bruno Weber, Michael Arand","doi":"10.1177/0271678X251333234","DOIUrl":"10.1177/0271678X251333234","url":null,"abstract":"Microsomal epoxide hydrolase (mEH), first identified as detoxifying enzyme, can hydrolyze epoxyeicosatrienoic acids (EETs) to less active diols (DHETs). EETs are potent vasodilatory and pro-angiogenic lipids, also implicated in neurovascular coupling. In mouse brain, mEH is strongly expressed in vascular and perivascular cells in contrast to the related soluble epoxide hydrolase (sEH), predominantly found in astrocytes. While sEH inhibition in stroke has demonstrated neuroprotective effects and increases cerebral blood flow (CBF), data regarding the role of mEH in brain are scarce. Here, we explored the function of mEH in cerebral vasculature by comparing mEH-KO, sEH-KO and WT mice. Basal cerebral volume (CBV0) was significantly higher in various mEH-KO brain areas compared to WT and sEH-KO. In line, quantification of cerebral vasculature in cortex and thalamus revealed a higher capillary density in mEH-KO, but not in sEH-KO brain. Whisker-stimulated CBF changes were by factor two higher in both mEH-KO and sEH-KO. In acutely isolated cerebral endothelial cells the loss of mEH, but not of sEH, augmented total EET levels and decreased the DHET:EET ratio. Collectively, these data suggest an important function of mEH in the regulation of cerebral vasculature and activity-modulated CBF, presumably by controlling local levels of endothelial-derived EETs.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1702-1716"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020846","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

Optimal filtering strategies for task-specific functional PET imaging. 特定任务功能PET成像的最佳过滤策略。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-09-01 Epub Date: 2025-04-02 DOI: 10.1177/0271678X251325668

Murray Bruce Reed, Magdalena Ponce de León, Sebastian Klug, Christian Milz, Leo Robert Silberbauer, Pia Falb, Godber Mathis Godbersen, Sharna Jamadar, Zhaolin Chen, Lukas Nics, Marcus Hacker, Rupert Lanzenberger, Andreas Hahn

{"title":"Optimal filtering strategies for task-specific functional PET imaging.","authors":"Murray Bruce Reed, Magdalena Ponce de León, Sebastian Klug, Christian Milz, Leo Robert Silberbauer, Pia Falb, Godber Mathis Godbersen, Sharna Jamadar, Zhaolin Chen, Lukas Nics, Marcus Hacker, Rupert Lanzenberger, Andreas Hahn","doi":"10.1177/0271678X251325668","DOIUrl":"10.1177/0271678X251325668","url":null,"abstract":"Functional Positron Emission Tomography (fPET) is an effective tool for studying dynamic processes in glucose metabolism and neurotransmitter action, providing insights into brain function and disease progression. However, optimizing signal processing to extract stimulation-specific information remains challenging. This study systematically evaluates state-of-the-art filtering techniques for fPET imaging. Forty healthy participants performed a cognitive task (Tetris®) during [18F]FDG PET/MR scans. Seven filtering techniques and multiple hyperparameters were tested: including 3D and 4D Gaussian smoothing, highly constrained backprojection (HYPR), iterative HYPR (IHYPR4D), MRI-Markov Random Field (MRI-MRF) filters, and dynamic/extended dynamic Non-Local Means (dNLM/edNLM). Filters were assessed based on test-retest reliability, task signal identifiability (temporal signal-to-noise ratio, tSNR), spatial task-based activation, and sample size calculations were assessed. Compared to 3D Gaussian smoothing, edNLM, dNLM, MRI-MRF L = 10, and IHYPR4D filters improved tSNR, while edNLM and HYPR enhanced test-retest reliability. Spatial task-based activation was enhanced by NLM filters and MRI-MRF approaches. The edNLM filter reduced the required sample size by 15.4%. Simulations supported these findings. This study highlights the strengths and limitations of fPET filtering techniques, emphasizing how hyperparamter adjustments affect outcome parameters. The edNLM filter shows promise with improved performance across all metrics, but filter selection should consider specific study objectives and resource constraints.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1760-1773"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772350","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