Journal of Cerebral Blood Flow and Metabolism最新文献_第6页

Metabolic preferences of astrocytes: Functional metabolic mapping reveals butyrate outcompetes acetate. 星形胶质细胞的代谢偏好：功能代谢图显示丁酸盐与乙酸盐竞争。

IF 5.4 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2024-09-28 DOI: 10.1177/0271678X241270457

Aishat O Ameen, Sebastian W Nielsen, Martin W Kjær, Jens V Andersen, Emil W Westi, Kristine K Freude, Blanca I Aldana

{"title":"Metabolic preferences of astrocytes: Functional metabolic mapping reveals butyrate outcompetes acetate.","authors":"Aishat O Ameen, Sebastian W Nielsen, Martin W Kjær, Jens V Andersen, Emil W Westi, Kristine K Freude, Blanca I Aldana","doi":"10.1177/0271678X241270457","DOIUrl":"10.1177/0271678X241270457","url":null,"abstract":"Disruptions to the gut-brain-axis have been linked to neurodegenerative disorders. Of these disruptions, reductions in the levels of short-chain fatty acids (SCFAs), like butyrate, have been observed in mouse models of Alzheimer's disease (AD). Butyrate supplementation in mice has shown promise in reducing neuroinflammation, amyloid-β accumulation, and enhancing memory. However, the underlying mechanisms remain unclear. To address this, we investigated the impact of butyrate on energy metabolism in mouse brain slices, primary cultures of astrocytes and neurons and in-vivo by dynamic isotope labelling with [U-13C]butyrate and [1,2-13C]acetate to map metabolism via mass spectrometry. Metabolic competition assays in cerebral cortical slices revealed no competition between butyrate and the ketone body, β-hydroxybutyrate, but competition with acetate. Astrocytes favoured butyrate metabolism compared to neurons, suggesting that the astrocytic compartment is the primary site of butyrate metabolism. In-vivo metabolism investigated in the 5xFAD mouse, an AD pathology model, showed no difference in 13C-labelling of TCA cycle metabolites between wild-type and 5xFAD brains, but butyrate metabolism remained elevated compared to acetate in both groups, indicating sustained uptake and metabolism in 5xFAD mice. Overall, these findings highlight the role of astrocytes in butyrate metabolism and the potential use of butyrate as an alternative brain fuel source.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241270457"},"PeriodicalIF":5.4,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347557","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 ferritin upregulation by deferiprone reduced neuronal ferroptosis and improved neurological deficits via NDRG1/Yap pathway in a neonatal rat model of germinal matrix hemorrhage. 在新生大鼠胚芽基质出血模型中，去铁酮通过NDRG1/Yap途径上调线粒体铁蛋白可减少神经元铁突变并改善神经功能缺损。

IF 5.4 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2024-09-24 DOI: 10.1177/0271678X241252110

Ye Yuan, Xiao Yang, Yutong Zhao, Jerry J Flores, Lei Huang, Lingui Gu, Ruihao Li, Xingyu Zhang, Shiyi Zhu, Siyuan Dong, Hideki Kanamaru, Qiuguang He, Yihao Tao, Kun Yi, Mingyang Han, Xionghui Chen, Lei Wu, John H Zhang, Zongyi Xie, Jiping Tang

{"title":"Mitochondrial ferritin upregulation by deferiprone reduced neuronal ferroptosis and improved neurological deficits via NDRG1/Yap pathway in a neonatal rat model of germinal matrix hemorrhage.","authors":"Ye Yuan, Xiao Yang, Yutong Zhao, Jerry J Flores, Lei Huang, Lingui Gu, Ruihao Li, Xingyu Zhang, Shiyi Zhu, Siyuan Dong, Hideki Kanamaru, Qiuguang He, Yihao Tao, Kun Yi, Mingyang Han, Xionghui Chen, Lei Wu, John H Zhang, Zongyi Xie, Jiping Tang","doi":"10.1177/0271678X241252110","DOIUrl":"10.1177/0271678X241252110","url":null,"abstract":"Ferroptosis contributes to brain injury after germinal matrix hemorrhage (GMH). Mitochondrial ferritin (FTMT), a novel mitochondrial outer membrane protein, reduces oxidative stress in neurodegenerative diseases. In vitro, Deferiprone has been shown to upregulate FTMT. However, the effects of FTMT upregulation by Deferiprone on neuronal ferroptosis after GMH and its underlying mechanism has not been investigated. In our study, 389 Sprague-Dawley rat pups of postnatal day 7 were used to establish a collagenase-induced GMH model and an iron-overload model of intracerebral FeCl2 injection. The brain expressions of FTMT, N-myc downstream-regulated gene-1 (NDGR1), Yes-associated protein (YAP), ferroptosis-related molecules including transferrin receptor (TFR) and acyl-CoA synthase long-chain family member 4 (ACSL4) were increased after GMH. FTMT agonist Deferiprone improved neurological deficits and hydrocephalus after GMH. Deferiprone or Adenovirus-FTMT enhanced YAP phosphorylation at the Ser127 site and attenuated ferroptosis, which was reversed by NDRG1 CRISPR Knockout. Iron overload induced neuronal ferroptosis and neurological deficits, which were improved by YAP CRISPR Knockout. Collectively, FTMT upregulation by Deferiprone reduced neuronal ferroptosis and neurological deficits via the NDRG1/YAP signaling pathway after GMH. Deferiprone may serve as a potential non-invasive treatment for GMH patients.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241252110"},"PeriodicalIF":5.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347558","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

Sigma-1 receptor signaling: A potential therapeutic approach for ischemic stroke. Sigma-1 受体信号传导：缺血性中风的潜在治疗方法。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2024-09-09 DOI: 10.1177/0271678X241281547

Alex Ngo, Nikolai Fattakhov, Michal Toborek

引用次数: 0

Neuroprotection with hypothermic reperfusion and extracorporeal cardiopulmonary resuscitation - A randomized controlled animal trial of prolonged ventricular fibrillation cardiac arrest in rats. 低体温再灌注和体外心肺复苏对神经的保护--对大鼠长时间心室颤动心脏骤停的随机对照动物试验。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2024-09-09 DOI: 10.1177/0271678X241281485

Ingrid Magnet, Alexandra-Maria Stommel, Christoph Schriefl, Matthias Mueller, Michael Poppe, Juergen Grafeneder, Christoph Testori, Andreas Janata, Andreas Schober, Daniel Grassmann, Wilhelm Behringer, Wolfgang Weihs, Michael Holzer, Sandra Hoegler, Florian Ettl

{"title":"Neuroprotection with hypothermic reperfusion and extracorporeal cardiopulmonary resuscitation - A randomized controlled animal trial of prolonged ventricular fibrillation cardiac arrest in rats.","authors":"Ingrid Magnet, Alexandra-Maria Stommel, Christoph Schriefl, Matthias Mueller, Michael Poppe, Juergen Grafeneder, Christoph Testori, Andreas Janata, Andreas Schober, Daniel Grassmann, Wilhelm Behringer, Wolfgang Weihs, Michael Holzer, Sandra Hoegler, Florian Ettl","doi":"10.1177/0271678X241281485","DOIUrl":"10.1177/0271678X241281485","url":null,"abstract":"Extracorporeal cardiopulmonary resuscitation (ECPR) facilitates resuscitation with immediate and precise temperature control. This study aimed to determine the optimal reperfusion temperature to minimize neurological damage after ventricular fibrillation cardiac arrest (VFCA). Twenty-four rats were randomized (n = 8 per group) to normothermia (NT = 37°C), mild hypothermia (MH = 33°C) or moderate hypothermia (MOD = 27°C). The rats were subjected to 10 minutes of VFCA, before 15 minutes of ECPR at their respective target temperature. After ECPR weaning, rats in the MOD group were rapidly rewarmed to 33°C, and temperature maintained at 33°C (MH/MOD) or 37°C (NT) for 12 hours before slow rewarming to normothermia (MH/MOD). The primary outcome was 30-day survival with overall performance category (OPC) 1 or 2 (1 = normal, 2 = slight disability, 3 = severe disability, 4 = comatose, 5 = dead). Secondary outcomes included awakening rate (OPC ≤ 3) and neurological deficit score (NDS, from 0 = normal to 100 = brain dead). The survival rate did not differ between reperfusion temperatures (NT = 25%, MH = 63%, MOD = 38%, p = 0.301). MH had the lowest NDS (NT = 4[IQR 3-4], MH = 2[1-2], MOD = 5[3-5], p = 0.044) and highest awakening rate (NT = 25%, MH = 88%, MOD = 75%, p = 0.024). In conclusion, ECPR with 33°C reperfusion did not statistically significantly improve survival after VFCA when compared with 37°C or 27°C reperfusion but was neuroprotective as measured by awakening rate and neurological function.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241281485"},"PeriodicalIF":4.9,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154213","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

Increased peripheral leukocyte aggravates brain injury and leads to poor outcome in stroke patients receiving intravenous thrombolysis: A study based on clinical evidence. 外周血白细胞增加加重脑损伤，导致接受静脉溶栓治疗的中风患者预后不佳：基于临床证据的研究。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2024-09-05 DOI: 10.1177/0271678X241281020

Ke-Jia Zhang, Yang Qu, Reziya Abuduxukuer, Peng Zhang, Yu Zhang, Jian-Hua Gao, Xian-Kun Zhang, Xiao-Dong Liu, Chun-Ying Li, Guang-Cai Li, Jun-Min Wang, Hui-Min Jin, Ying He, Li-Gang Jiang, Liang Liu, Yongfei Jiang, Rui-Hong Teng, Yan Jia, Bai-Jing Zhang, Zhi-Bo Chen, Yingbin Qi, Xiu-Ping Liu, Song Li, Thanh N Nguyen, Yi Yang, Zhen-Ni Guo

{"title":"Increased peripheral leukocyte aggravates brain injury and leads to poor outcome in stroke patients receiving intravenous thrombolysis: A study based on clinical evidence.","authors":"Ke-Jia Zhang, Yang Qu, Reziya Abuduxukuer, Peng Zhang, Yu Zhang, Jian-Hua Gao, Xian-Kun Zhang, Xiao-Dong Liu, Chun-Ying Li, Guang-Cai Li, Jun-Min Wang, Hui-Min Jin, Ying He, Li-Gang Jiang, Liang Liu, Yongfei Jiang, Rui-Hong Teng, Yan Jia, Bai-Jing Zhang, Zhi-Bo Chen, Yingbin Qi, Xiu-Ping Liu, Song Li, Thanh N Nguyen, Yi Yang, Zhen-Ni Guo","doi":"10.1177/0271678X241281020","DOIUrl":"10.1177/0271678X241281020","url":null,"abstract":"Whether the dynamic development of peripheral inflammation aggravates brain injury and leads to poor outcome in stroke patients receiving intravenous thrombolysis (IVT), remains unclear and warrants further study. In this study, total of 1034 patients with acute ischemic stroke who underwent IVT were enrolled. Serum leukocyte variation (whether increase from baseline to 24 h after IVT), National Institutes of Health Stroke Scale (NIHSS), infarct volume, early neurologic deterioration (END), the unfavorable outcome at 3-month (modified Rankin Scale [mRS] score ≥3) and mortality were recorded. Serum brain injury biomarkers, including Glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), S100β, neuron-specific enolase (NSE), were measured to reflect the extent of brain injury. We found that patients with increased serum leukocytes had elevated brain injury biomarkers (GFAP, UCH-L1, and S100β), larger infarct volume, higher 24 h NIHSS, higher proportion of END, unfavorable outcome and mortality. Furthermore, an increase in serum leukocytes was independently associated with infarct volume, 24 h NIHSS, END, and unfavorable outcome at 3 months, and serum UCH-L1, S100β, and NSE levels. These results suggest that an increase in serum leukocytes indicates severe brain injury and may be used to predict the outcome of patients with ischemic stroke who undergo IVT.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241281020"},"PeriodicalIF":4.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132859","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

Estimation of cerebrovascular reactivity amplitude and lag using breath-holding fMRI and the global BOLD signal: Application in diabetes and hypertension. 利用屏气 fMRI 和全局 BOLD 信号估算脑血管反应幅度和滞后：在糖尿病和高血压中的应用。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2024-09-03 DOI: 10.1177/0271678X241270420

Nuwan D Nanayakkara, Liesel-Ann Meusel, Nicole D Anderson, J Jean Chen

{"title":"Estimation of cerebrovascular reactivity amplitude and lag using breath-holding fMRI and the global BOLD signal: Application in diabetes and hypertension.","authors":"Nuwan D Nanayakkara, Liesel-Ann Meusel, Nicole D Anderson, J Jean Chen","doi":"10.1177/0271678X241270420","DOIUrl":"10.1177/0271678X241270420","url":null,"abstract":"In this work, we demonstrate a data-driven approach for estimating cerebrovascular reactivity (CVR) amplitude and lag from breathhold (BH) fMRI data alone. Our approach employs a frequency-domain approach that is independent of external recordings. CVR amplitude is estimated from the BOLD frequency spectrum and CVR lag is estimated from the Fourier phase using the global-mean BOLD signal as reference. Unlike referencing to external recordings, these lags are specific to the brain. We demonstrated our method in detecting regional CVR amplitude and lag differences across healthy (CTL), hypertensive (HT) and hypertension-plus-type-2-diabetes (HT + DM) groups of similar ages and sex ratios, with a total N of 49. We found CVR amplitude to be significantly higher in CTL compared to HT + DM, with minimal difference between CTL and HT. Also, voxelwise CVR lag estimated in the Fourier domain is a more sensitive marker of vascular dysfunction than CVR amplitude. CVR lag in HT is significantly shorter than in CTL, with minimal difference between CTL and HT + DM. Our results support the importance of joint CVR amplitude and lag assessments in clinical applications.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241270420"},"PeriodicalIF":4.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119918","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

Serotonergic regulation of cortical neurovascular coupling and hemodynamics upon awakening from sleep in mice. 小鼠从睡眠中苏醒后大脑皮层神经血管耦合和血液动力学的血清素能调节。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2024-09-01 Epub Date: 2024-03-13 DOI: 10.1177/0271678X241238843

Akiyo Natsubori, Soojin Kwon, Yoshiko Honda, Takashi Kojima, Akihiro Karashima, Kazuto Masamoto, Makoto Honda

{"title":"Serotonergic regulation of cortical neurovascular coupling and hemodynamics upon awakening from sleep in mice.","authors":"Akiyo Natsubori, Soojin Kwon, Yoshiko Honda, Takashi Kojima, Akihiro Karashima, Kazuto Masamoto, Makoto Honda","doi":"10.1177/0271678X241238843","DOIUrl":"10.1177/0271678X241238843","url":null,"abstract":"Neurovascular coupling (NVC) is the functional hyperemia of the brain responding to local neuronal activity. It is mediated by astrocytes and affected by subcortical ascending pathways in the cortex that convey information, such as sensory stimuli and the animal condition. Here, we investigate the influence of the raphe serotonergic system, a subcortical ascending arousal system in animals, on the modulation of cortical NVC and cerebral blood flow (CBF). Raphe serotonergic neurons were optogenically activated for 30 s, which immediately awakened the mice from non-rapid eye movement sleep. This caused a biphasic cortical hemodynamic change: a transient increase for a few seconds immediately after photostimulation onset, followed by a large progressive decrease during the stimulation period. Serotonergic neuron activation increased intracellular Ca2+ levels in cortical pyramidal neurons and astrocytes, demonstrating its effect on the NVC components. Pharmacological inhibition of cortical neuronal firing activity and astrocyte metabolic activity had small hypovolemic effects on serotonin-induced biphasic CBF changes, while blocking 5-HT1B receptors expressed primarily in cerebral vasculature attenuated the decreasing CBF phase. This suggests that serotonergic neuron activation leading to animal awakening could allow the NVC to exert a hyperemic function during a biphasic CBF response, with a predominant decrease in the cortex.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1591-1607"},"PeriodicalIF":4.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140110377","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 effectiveness and safety of human urinary kallidinogenase in acute ischemic stroke patients undergoing endovascular therapy. 接受血管内治疗的急性缺血性脑卒中患者服用人尿液凯利苷原酶的有效性和安全性。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2024-09-01 Epub Date: 2024-03-09 DOI: 10.1177/0271678X241238033

Mengmeng Wang, Changwei Guo, Jie Yang, Jing Li, Jinrong Hu, Zhouzhou Peng, Meng Guo, Lingyu Zhang, Fengli Li, Qingwu Yang, Wenjie Zi, Pengfei Wang

{"title":"The effectiveness and safety of human urinary kallidinogenase in acute ischemic stroke patients undergoing endovascular therapy.","authors":"Mengmeng Wang, Changwei Guo, Jie Yang, Jing Li, Jinrong Hu, Zhouzhou Peng, Meng Guo, Lingyu Zhang, Fengli Li, Qingwu Yang, Wenjie Zi, Pengfei Wang","doi":"10.1177/0271678X241238033","DOIUrl":"10.1177/0271678X241238033","url":null,"abstract":"The effectiveness and safety of human urinary kallidinogenase (HUK) in acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT) due to large vessel occlusion (LVO) was unclear. A pooled analysis was performed using individual data from the DEVT and RESCUE BT trials. Patients were divided into two groups based on HUK treatment. The primary outcome was the 90-day modified Rankin Scale (mRS) score. Safety outcomes included 90-day mortality and symptomatic intracranial hemorrhage (sICH) within 48 hours. A total of 1174 patients were included in the study. Of these, 150 (12.8%) patients received HUK. The adjusted common odds ratio (OR) of the mRS score was 1.458 (95% confidence interval [CI] = 1.072-1.983; p = 0.016) favoring HUK. The incidence of sICH (2.0% vs. 8.6%; adjusted OR: 0.198; 95% CI: 0.061-0.638; p = 0.007) and mortality (11.3% vs.18.5%; adjusted OR: 0.496; 95% CI: 0.286-0.862; p = 0.013) was lower in HUK group than non-HUK group. This association was consistent with propensity score-matching and the inverse probability of treatment weighting analysis. In conclusion, HUK was safe and associated with a preferable prognosis in AIS patients due to LVO in the anterior circulation.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1565-1576"},"PeriodicalIF":4.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068422","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

Macro- and microvascular contributions to cerebral structural alterations in patients with asymptomatic carotid artery stenosis. 大血管和微血管对无症状颈动脉狭窄患者脑结构改变的影响。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2024-09-01 Epub Date: 2024-03-20 DOI: 10.1177/0271678X241238935

Lena Schmitzer, Stephan Kaczmarz, Jens Göttler, Gabriel Hoffmann, Michael Kallmayer, Hans-Henning Eckstein, Dennis Martin Hedderich, Jan Kufer, Claus Zimmer, Christine Preibisch, Fahmeed Hyder, Nico Sollmann

{"title":"Macro- and microvascular contributions to cerebral structural alterations in patients with asymptomatic carotid artery stenosis.","authors":"Lena Schmitzer, Stephan Kaczmarz, Jens Göttler, Gabriel Hoffmann, Michael Kallmayer, Hans-Henning Eckstein, Dennis Martin Hedderich, Jan Kufer, Claus Zimmer, Christine Preibisch, Fahmeed Hyder, Nico Sollmann","doi":"10.1177/0271678X241238935","DOIUrl":"10.1177/0271678X241238935","url":null,"abstract":"Atherosclerosis can underly internal carotid artery stenosis (ICAS), a major risk factor for ischemic stroke, as well as small vessel disease (SVD). This study aimed to investigate hemodynamics and structural alterations associated with SVD in ICAS patients. 28 patients with unilateral asymptomatic ICAS and 30 age-matched controls underwent structural (T1-/T2-weighted and diffusion tensor imaging [DTI]) and hemodynamic (pseudo-continuous arterial spin labeling and dynamic susceptibility contrast) magnetic resonance imaging. SVD-related alterations were assessed using free water (FW), FW-corrected DTI, and peak-width of skeletonized mean diffusivity (PSMD). Furthermore, cortical thickness, cerebral blood flow (CBF), and capillary transit time heterogeneity (CTH) were analyzed. Ipsilateral to the stenosis, cortical thickness was significantly decreased in the posterior dorsal cingulate cortex (p = 0.024) and temporal pole (p = 0.028). ICAS patients exhibited elevated PSMD (p = 0.005), FW (p < 0.001), and contralateral alterations in FW-corrected DTI metrics. We found significantly lateralized CBF (p = 0.011) and a tendency for lateralized CTH (p = 0.067) in the white matter (WM) related to ICAS. Elevated PSMD and FW may indicate a link between SVD and WM changes. Contralateral alterations were seen in FW-corrected DTI, whereas hemodynamic and cortical changes were mainly ipsilateral, suggesting SVD might influence global brain changes concurrent with ICAS-related hemodynamic alterations.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1629-1642"},"PeriodicalIF":4.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174942","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

Cpeb4-mediated Dclk2 promotes neuronal pyroptosis induced by chronic cerebral ischemia through phosphorylation of Ehf. Cpeb4介导的Dclk2通过磷酸化Ehf促进慢性脑缺血诱导的神经元热解。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2024-09-01 Epub Date: 2024-03-21 DOI: 10.1177/0271678X241240590

Miao Sun, Xin Huang, Xuelei Ruan, Xiuli Shang, Mengyang Zhang, Libo Liu, Ping Wang, Ping An, Yang Lin, Jin Yang, Yixue Xue

{"title":"Cpeb4-mediated Dclk2 promotes neuronal pyroptosis induced by chronic cerebral ischemia through phosphorylation of Ehf.","authors":"Miao Sun, Xin Huang, Xuelei Ruan, Xiuli Shang, Mengyang Zhang, Libo Liu, Ping Wang, Ping An, Yang Lin, Jin Yang, Yixue Xue","doi":"10.1177/0271678X241240590","DOIUrl":"10.1177/0271678X241240590","url":null,"abstract":"Chronic cerebral ischemia (CCI) is a clinical syndrome characterised by brain dysfunction due to decreased chronic cerebral perfusion. CCI initiates several inflammatory pathways, including pyroptosis. RNA-binding proteins (RBPs) play important roles in CCI. This study aimed to explore whether the interaction between RBP-Cpeb4 and Dclk2 affected Ehf phosphorylation to regulate neuronal pyroptosis. HT22 cells and mice were used to construct oxygen glucose deprivation (OGD)/CCI models. We found that Cpeb4 and Dclk2 were upregulated in OGD-treated HT22 cells and CCI-induced hippocampal CA1 tissues. Cpeb4 upregulated Dclk2 expression by increasing Dclk2 mRNA stability. Knockdown of Cpeb4 or Dclk2 inhibited neuronal pyroptosis in OGD-treated HT22 cells and CCI-induced hippocampal CA1 tissues. By binding to the promoter regions of Caspase1 and Caspase3, the transcription factor Ehf reduced their promoter activities and inhibited the transcription. Dclk2 phosphorylated Ehf and changed its nucleoplasmic distribution, resulting in the exit of p-Ehf from the nucleus and decreased Ehf levels. It promoted the expression of Caspase1 and Caspase3 and stimulated neuronal pyroptosis of HT22 cells induced by OGD. Cpeb4/Dclk2/Ehf pathway plays an important role in the regulation of cerebral ischemia-induced neuronal pyroptosis.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1655-1673"},"PeriodicalIF":4.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184561","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