Journal of Cerebral Blood Flow and Metabolism最新文献

Type 2 diabetes abates retrograde collateral flow and promotes leukocyte adhesion following ischemic stroke. 2型糖尿病减少缺血性卒中后逆行侧枝血流并促进白细胞粘附。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-29 DOI: 10.1177/0271678X251338203

Yoshimichi Sato, Yuya Kato, Atsushi Kanoke, Jennifer Y Sun, Yasuo Nishijima, Ruikang K Wang, Michael Stryker, Hidenori Endo, Jialing Liu

{"title":"Type 2 diabetes abates retrograde collateral flow and promotes leukocyte adhesion following ischemic stroke.","authors":"Yoshimichi Sato, Yuya Kato, Atsushi Kanoke, Jennifer Y Sun, Yasuo Nishijima, Ruikang K Wang, Michael Stryker, Hidenori Endo, Jialing Liu","doi":"10.1177/0271678X251338203","DOIUrl":"https://doi.org/10.1177/0271678X251338203","url":null,"abstract":"Type 2 diabetes mellitus (T2DM) is associated with impaired leptomeningeal collateral compensation and poor stroke outcome. Neutrophils tethering and rolling on endothelium after stroke can also independently reduce flow velocity. However, the chronology and topological changes in collateral circulation in T2DM is not yet defined. Here, we describe the spatial and temporal blood flow dynamics and vessel diameter changes in pial arteries and veins and leukocyte-endothelial adhesion following middle cerebral artery (MCA) stroke using two-photon microscopy in awake control and T2DM mice. Relative to control mice, T2DM mice already exhibited smaller pial vessels with reduced flow velocity prior to stroke. Following stroke, T2DM mice displayed persistently reduced blood flow in pial arteries and veins, resulting in a poor recovery of downstream penetrating arterial flow and a sustained deficit in microvascular flow. There was also persistent increase of leukocyte adhesion to the endothelium of veins, coincided with elevated neutrophils infiltration into brain parenchyma in T2DM mice compared to control mice after stroke. Our data suggest that T2DM-induced increase in inflammation and chronic remodeling of leptomeningeal vessels may contribute to the observed hemodynamics deficiency after stroke and subsequent poor stroke outcome.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251338203"},"PeriodicalIF":4.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering the brain glucose metabolism: A gateway to innovative stroke therapies. 解读脑葡萄糖代谢：创新中风治疗的途径。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-29 DOI: 10.1177/0271678X251346277

Didier F Pisani, Nicolas Blondeau

{"title":"Deciphering the brain glucose metabolism: A gateway to innovative stroke therapies.","authors":"Didier F Pisani, Nicolas Blondeau","doi":"10.1177/0271678X251346277","DOIUrl":"https://doi.org/10.1177/0271678X251346277","url":null,"abstract":"Stroke is the leading cause of physical disability and death among adults in most Western countries. Consecutive to a vascular occlusion, cells face a brutal reduction in supply of oxygen and glucose and thus an energy failure, which in turn triggers cell death mechanisms. Among brain cells, neurons are the most susceptible to ischemia because of their high metabolic demand and low reservoir of energy substrates. In neurons, glycolysis uses glucose coming from blood or from glycogen stored in astrocytes, underlying the deep astrocyte-neuron metabolic cooperation. During ischemia, both the aerobic and anaerobic pathways and thus energy production are compromised, which disrupts proper cell functioning, notably Na+/K+ ATPase and mitochondria. This results in altered Ca2+ homeostasis and overproduction of ROS, the latter being further exacerbated during the reperfusion phase. Consequently, glucose metabolism in the different brain cell populations plays a central role in injury and recovery after stroke, and has recently emerged as a promising target for therapeutic intervention. In this context, the overall objective of this article is to review the interconnections between stroke and brain glucose metabolism and to explore how its targeting may offer new therapeutic opportunities in addressing the global stroke epidemic.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251346277"},"PeriodicalIF":4.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Repeatability and reliability of cerebrovascular reactivity in young adults using multi-echo, multi-contrast MRI. 使用多回声、多对比MRI对年轻人脑血管反应性的可重复性和可靠性。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-25 DOI: 10.1177/0271678X251345292

Elizabeth G Keeling, Maurizio Bergamino, Lauren R Ott, Molly M McElvogue, Ashley M Stokes

{"title":"Repeatability and reliability of cerebrovascular reactivity in young adults using multi-echo, multi-contrast MRI.","authors":"Elizabeth G Keeling, Maurizio Bergamino, Lauren R Ott, Molly M McElvogue, Ashley M Stokes","doi":"10.1177/0271678X251345292","DOIUrl":"10.1177/0271678X251345292","url":null,"abstract":"Cerebrovascular reactivity (CVR) shows promise as a biomarker of vascular integrity and may benefit from a repeatable, reliable, and microvasculature-sensitive acquisition. A combined spin- and gradient-echo (SAGE) functional MRI (fMRI) acquisition may improve repeatability and reliability compared to single spin- (SE) and gradient-echo (GRE) fMRI and provide a microvascular-weighted analysis. The most repeatable and reliable MRI acquisition CVR maps were compared across three CVR paradigms: a breath-hold task, a breath modulation task, and a resting state acquisition. SAGE-fMRI data was acquired in fifteen young adults at two timepoints. Mean gray matter (GM) within-subject coefficient of variation (wCV) and intraclass correlation coefficient (ICC) were compared within the quantitative and weighted SAGE-fMRI CVR maps and single GRE- and SE-fMRI CVR. Total and microvascular MRI inputs with lowest wCV and highest ICC were used to compare three CVR paradigms. Total and microvascular weighted SAGE-fMRI CVR had the lowest wCV and highest ICC across paradigms. The breath-hold paradigm produced significantly higher GM CVR estimates. SAGE repeatably and reliably measures CVR and offers a simultaneous, complementary analysis on total and microvascular scales. The breath-hold paradigm showed significantly higher CVR estimates, but less compliance-dependent protocols may be ideal for applications in patient populations.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251345292"},"PeriodicalIF":4.9,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub 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":"271678X251345360"},"PeriodicalIF":4.9,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub 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":"271678X251345293"},"PeriodicalIF":4.9,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chronic treatment with adenosine A1 receptor antagonist promotes neurogenesis and improves outcome after cerebral ischemia. 长期使用腺苷A1受体拮抗剂可促进脑缺血后神经发生并改善预后。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-24 DOI: 10.1177/0271678X251345294

Maria Ardaya, Monica Benito-Muñoz, Esther Rubio-López, Maider Garbizu, Laura Aguado, Naroa Mocha-Muñoz, Leyre Iglesias, Unai Aldutzin, Carlos Matute, Federico N Soria, Vanessa Gómez-Vallejo, Aitzol García-Etxarri, Jordi Llop, Fabio Cavaliere, Abraham Martín

{"title":"Chronic treatment with adenosine A1 receptor antagonist promotes neurogenesis and improves outcome after cerebral ischemia.","authors":"Maria Ardaya, Monica Benito-Muñoz, Esther Rubio-López, Maider Garbizu, Laura Aguado, Naroa Mocha-Muñoz, Leyre Iglesias, Unai Aldutzin, Carlos Matute, Federico N Soria, Vanessa Gómez-Vallejo, Aitzol García-Etxarri, Jordi Llop, Fabio Cavaliere, Abraham Martín","doi":"10.1177/0271678X251345294","DOIUrl":"10.1177/0271678X251345294","url":null,"abstract":"Adenosine A1 receptors (A1ARs) are promising targets for stroke treatment, potentially due to their relatively unexplored effects on proliferation and differentiation of newborn neurons. In this study, we investigated the impact of chronic treatment with the A1ARs antagonist DPCPX on neurogenesis following MCAO in rodents, using PET with [18F]FLT in rats and immunohistochemistry in mice. In addition, we assessed the therapeutic properties of DPCPX on stroke recovery with a comprehensive battery of neurological and behavioral tests. The outcome shows that blocking A1ARs signaling with DPCPX improved immunohistochemical results in 8 to 28 days after MCAO in mice. PET imaging with [18F]FLT revealed an increase in cellular proliferation following DPCPX treatment in the subventricular zone at day 8 post-ischemia in rats, a result further supported by IHC in SVZ of ischemic animals. Furthermore, DPCPX enhanced the production and integration of newborn neurons while reducing astrocytic differentiation in the ischemic areas. Finally, behavioral tests showed that chronic treatment with DPCPX ameliorated motor and memory deficits after brain ischemia. All taken in consideration, our results provide novel and compelling evidence of the therapeutic potential of the A1AR antagonist DPCPX for ischemic stroke recovery.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251345294"},"PeriodicalIF":4.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135917","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

Exploring differences in circulating metabolites of females and males with Alzheimer's disease. 探讨老年痴呆症女性和男性循环代谢物的差异。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-16 DOI: 10.1177/0271678X251340513

Sara Serafini, Antonella Angiolillo, Gabriella Ferretti, Giulia Viviani, Carmela Matrone, Alfonso Di Costanzo

{"title":"Exploring differences in circulating metabolites of females and males with Alzheimer's disease.","authors":"Sara Serafini, Antonella Angiolillo, Gabriella Ferretti, Giulia Viviani, Carmela Matrone, Alfonso Di Costanzo","doi":"10.1177/0271678X251340513","DOIUrl":"10.1177/0271678X251340513","url":null,"abstract":"Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to cognitive and functional decline and primarily affects the elderly population. Metabolic alterations, particularly in the amino acid and fatty acid pathways, are increasingly being recognized in AD. However, the role of sex in these metabolic changes remains insufficiently understood, despite evidence suggesting that AD may manifest more strongly in females. This study investigated sex-specific metabolic patterns in AD by analyzing routine and non-routine hematological tests, including amino acids and fatty acid profiles. The results showed that certain metabolites such as citrulline and alanine were frequently altered in patients with AD. Notably, docosahexaenoic acid, dihomo-gamma-linolenic acid, and gamma-linolenic acid levels were exclusively elevated in female patients. Additionally, females exhibited significantly lower Aβ42 and higher gamma-linolenic acid levels than males, with the trend becoming more pronounced during the early stages of the disease. Despite these differences, most metabolic markers did not show significant sex-based variation. These findings suggest that while some sex-specific metabolic differences exist in AD, a larger cohort is needed to confirm these patterns and fully understand the influence of sex on AD-related metabolic changes.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251340513"},"PeriodicalIF":4.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078362","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

FTO promotes post-stroke neuroprotection by m⁶A demethylation of c-Jun. FTO通过c-Jun的m6A去甲基化促进脑卒中后神经保护。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-15 DOI: 10.1177/0271678X251340808

Anil K Chokkalla, Suresh L Mehta, Soomin Jeong, Hui-Lung Sun, Qing Dai, Raghu Vemuganti

{"title":"FTO promotes post-stroke neuroprotection by m6A demethylation of c-Jun.","authors":"Anil K Chokkalla, Suresh L Mehta, Soomin Jeong, Hui-Lung Sun, Qing Dai, Raghu Vemuganti","doi":"10.1177/0271678X251340808","DOIUrl":"10.1177/0271678X251340808","url":null,"abstract":"N6-methyladenosine (m6A) is a critical epitranscriptomic regulator of neuronal function. Cerebral ischemia induces m6A hypermethylation due to decreased expression of m6A demethylase fat mass and obesity-associated (FTO) protein. Previously, we showed that cerebral overexpression of FTO with an adeno-associated virus (AAV) 9 protects the post-stroke brain. We presently evaluated the mechanistic basis for FTO-dependent m6A demethylation in post-ischemic neuroprotection using the mice transient middle cerebral artery occlusion model of experimental stroke. Based on the bioinformatic predictions and m6A abundance, pro-apoptotic transcription factor Jun proto-oncogene (c-Jun) with 19 m6A sites was chosen as an exemplary target. FTO overexpression normalized the post-stroke m6A hypermethylation of c-Jun without altering its transcript levels. FTO-dependent m6A demethylation suppressed translation of c-Jun. Consequently, several c-Jun target genes are transcriptionally repressed, and the post-ischemic neuronal apoptosis is decelerated, as seen by decreased cleaved caspase-3 levels and TUNEL+ neurons in the FTO AAV9 treated group compared to the control AAV9 treated group. Moreover, replenishing c-Jun precluded the FTO-mediated post-stroke neuroprotection and functional recovery. Collectively, this study demonstrated that the FTO/m6A/c-Jun axis ameliorates post-stroke neuronal apoptosis and brain damage, leading to better functional outcomes.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251340808"},"PeriodicalIF":4.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078364","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

Amplitude fluctuations of cerebrovascular oscillations and CSF movement desynchronize during NREM3 sleep. NREM3期睡眠时脑血管振荡振幅波动和脑脊液运动不同步。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-15 DOI: 10.1177/0271678X251337637

Vidhya V Nair, Brianna R Kish, Hideyuki Oshima, Adam M Wright, Qiuting Wen, A J Schwichtenberg, Yunjie Tong

{"title":"Amplitude fluctuations of cerebrovascular oscillations and CSF movement desynchronize during NREM3 sleep.","authors":"Vidhya V Nair, Brianna R Kish, Hideyuki Oshima, Adam M Wright, Qiuting Wen, A J Schwichtenberg, Yunjie Tong","doi":"10.1177/0271678X251337637","DOIUrl":"10.1177/0271678X251337637","url":null,"abstract":"Fluctuations in cerebral blood volume (CBV) are a dominant mechanism aiding cerebrospinal fluid (CSF) movement in the brain during wakefulness and non-rapid eye movement (NREM) sleep. However, it is unclear if the amplitudes of CBV oscillations also change in proportion to the changes in amplitude of CSF movement across specific NREM sleep states. It is also not known if the coupling strength between them varies between NREM sleep states. To investigate these relationships, we measured cerebral hemodynamics and craniad CSF movement at the fourth ventricle simultaneously during wakefulness and NREM sleep states using concurrent Electroencephalography and functional Magnetic Resonance Imaging. We found that the amplitude fluctuations of cerebral hemodynamics and CSF oscillations desynchronize from one another only during deep NREM3 state, despite the strong mechanical coupling between CBV changes and CSF movement, which was consistent across all states. This suggests the existence of a different mechanism, linked to the cortical interstitial volume/resistance change, that regulates the NREM3 CSF inflow into the brain.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251337637"},"PeriodicalIF":4.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078328","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

Mitochondrial unfolded protein response (UPR^mt) as novel therapeutic targets for neurological disorders. 线粒体未折叠蛋白反应（UPRmt）作为神经系统疾病的新治疗靶点。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-15 DOI: 10.1177/0271678X251341293

Xi Chen, Hong An, Jiachen He, Jiaqi Guo, Shuaili Xu, Chuanjie Wu, Di Wu, Xunming Ji

{"title":"Mitochondrial unfolded protein response (UPRmt) as novel therapeutic targets for neurological disorders.","authors":"Xi Chen, Hong An, Jiachen He, Jiaqi Guo, Shuaili Xu, Chuanjie Wu, Di Wu, Xunming Ji","doi":"10.1177/0271678X251341293","DOIUrl":"10.1177/0271678X251341293","url":null,"abstract":"Neurological disorders, including brain cancer, neurodegenerative diseases and ischemic/reperfusion injury, pose a significant threat to global human health. Due to the high metabolic demands of nerve cells, mitochondrial dysfunction is a critical feature of these disorders. The mitochondrial unfolded protein response (UPRmt) is an evolutionarily conserved mitochondrial response, which is critical for maintaining mitochondrial and energetic homeostasis under stress. Previous studies have found that UPRmt participates in diverse physiological processes especially metabolism and immunity. Currently, increasing evidence suggest that targeted regulation of UPRmt can also effectively delay the progression of neurological diseases and improve patients' prognosis. This review provides a comprehensive overview of UPRmt in the context of neurological diseases, with a particular emphasis on its regulatory functions. Additionally, we summarize the mechanistic insights into UPRmt in neurological disorders as investigated in preclinical studies, as well as its potential as a therapeutic target in the clinical management of neurological tumors. By highlighting the importance of UPRmt in the complex processes underlying neurological disorders, this review aims to bridge current knowledge gaps and inspire novel therapeutic strategies for these conditions.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251341293"},"PeriodicalIF":4.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078366","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