Journal of Cerebral Blood Flow & Metabolism最新文献

Orthostatic hypotension and cerebral small vessel disease: A systematic review 直立性低血压与脑小血管疾病：系统回顾

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2024-09-17 DOI: 10.1177/0271678x241283226

Julia HI Wiersinga, Frank J Wolters, Mike JL Peters, Hanneke FM Rhodius-Meester, Marijke C Trappenburg, Majon Muller

{"title":"Orthostatic hypotension and cerebral small vessel disease: A systematic review","authors":"Julia HI Wiersinga, Frank J Wolters, Mike JL Peters, Hanneke FM Rhodius-Meester, Marijke C Trappenburg, Majon Muller","doi":"10.1177/0271678x241283226","DOIUrl":"https://doi.org/10.1177/0271678x241283226","url":null,"abstract":"Orthostatic hypotension(OH) is highly prevalent in ageing populations and may contribute to cognitive decline through cerebral small vessel disease(CSVD). Research on the association between OH and CSVD is fragmented and inconsistent. We systematically reviewed the literature for studies assessing the association between OH and CSVD, published until December 1st 2023 in MEDLINE, PubMed or Web of Science. We included studies with populations aged ≥60, that assessed OH in relation to CSVD including white matter hyperintensities(WMH), lacunes and cerebral microbleeds. Modified JBI checklist was used to assess risk of bias. A narrative synthesis of the results was presented. Of 3180 identified studies, eighteen were included. Fifteen studies reported on WMH, four on lacunes, seven on microbleeds. Six of fifteen studies on WMH found that OH was related to an increased burden of WMH, neither longitudinal studies found associations with WMH progression. Findings were inconsistent across studies concerning lacunes and microbleeds. Across outcomes, adequate adjustment for systolic blood pressure tended to coincide with smaller effect estimates. Current evidence on the OH-CSVD association originates mostly from cross-sectional studies, providing inconsistent and inconclusive results. Longitudinal studies using standardized and fine-grained assessment of OH and CSVD and adequate adjustment for supine blood pressure are warranted.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The relative associations of aortic and carotid artery stiffness with CeVD and cognition 主动脉和颈动脉僵化与心血管疾病和认知的相对关系

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2024-09-10 DOI: 10.1177/0271678x241281137

Caroline Robert, Lieng-Hsi Ling, Eugene SJ Tan, Narayanaswamy Venketasubramanian, Shir Lynn Lim, Lingli Gong, Josephine Lunaria Berboso, Arthur Mark Richards, Christopher Chen, Saima Hilal

{"title":"The relative associations of aortic and carotid artery stiffness with CeVD and cognition","authors":"Caroline Robert, Lieng-Hsi Ling, Eugene SJ Tan, Narayanaswamy Venketasubramanian, Shir Lynn Lim, Lingli Gong, Josephine Lunaria Berboso, Arthur Mark Richards, Christopher Chen, Saima Hilal","doi":"10.1177/0271678x241281137","DOIUrl":"https://doi.org/10.1177/0271678x241281137","url":null,"abstract":"We examined the relative associations of aortic and carotid artery stiffness with cerebrovascular disease (CeVD), cognition, and dementia subtypes in a memory clinic cohort of 272 participants (mean age = 75.4, SD = 6.8). We hypothesized that carotid artery stiffness would have greater effects on outcomes, given its proximate relationship to the brain. Aortic and carotid artery stiffness were assessed with applanation tonometry and carotid ultrasonography, respectively. CeVD markers included white matter hyperintensities (WMH), lacunes, cerebral microbleeds, cortical infarcts, and intracranial stenosis. Cognition was assessed by the Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and a neuropsychological battery. Multivariable linear regression was conducted to determine associations of arterial stiffness with WMH and cognition, while logistic regression analysed associations with CeVD markers and dementia subtypes. Carotid artery stiffness z-score was associated with WMH, cortical infarcts, vascular cognitive impairment, and MMSE, independent of age, sex, education, vascular risk factors, and aortic stiffness z-score. Although aortic stiffness z-score was independently associated with cortical infarcts, this became non-significant after further adjusting for carotid artery stiffness z-score. We found that carotid artery stiffness had greater effects on CeVD, cognitive function and impairment in memory clinic patients compared to aortic stiffness.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"11 1","pages":"271678X241281137"},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Detectability of white matter cerebral blood flow using arterial spin labeling MRI in patients with sickle cell disease: Relevance of flow territory, bolus arrival time, and hematocrit 利用动脉自旋标记磁共振成像检测镰状细胞病患者的脑白质血流：血流区域、血栓到达时间和血细胞比容的相关性

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2024-09-10 DOI: 10.1177/0271678x241270283

Wesley T Richerson, Megan Aumann, Alexander K Song, Jarrod J Eisma, Samantha Davis, Lauren Milner, Maria Garza, L Taylor Davis, Dann Martin, Lori C Jordan, Manus J Donahue

{"title":"Detectability of white matter cerebral blood flow using arterial spin labeling MRI in patients with sickle cell disease: Relevance of flow territory, bolus arrival time, and hematocrit","authors":"Wesley T Richerson, Megan Aumann, Alexander K Song, Jarrod J Eisma, Samantha Davis, Lauren Milner, Maria Garza, L Taylor Davis, Dann Martin, Lori C Jordan, Manus J Donahue","doi":"10.1177/0271678x241270283","DOIUrl":"https://doi.org/10.1177/0271678x241270283","url":null,"abstract":"Sickle cell disease (SCD) is the most common genetic blood disorder, characterized by red cell hemolysis, anemia, and corresponding increased compensatory cerebral blood flow (CBF). SCD patients are at high risk for cerebral infarcts and CBF quantification is likely critical to assess infarct risk. Infarcts primarily localize to white matter (WM), yet arterial spin labeling (ASL) MRI, the most common non-invasive CBF approach, has poor WM CBF sensitivity owing to low WM CBF and long WM bolus arrival time (BAT). We hypothesize that anemia, and associated cerebral hyperemia, in SCD leads to improved WM detection with ASL. We performed 3-Tesla multi-delay pulsed ASL in SCD (n = 35; age = 30.5 ± 8.3 years) and control (n = 15; age = 28.7 ± 4.5 years) participants and applied t-tests at each inversion time within different flow territories, and determined which regions were significantly above noise floor (criteria: one-sided p < 0.05). Total WM CBF-weighted signal was primarily detectable outside of borderzone regions in SCD (CBF = 17.7 [range = 12.9–25.0] mL/100 g/min), but was largely unphysiological in control (CBF = 8.1 [range = 7.6–9.9)] mL/100 g/min) participants. WM BAT was reduced in SCD versus control participants (ΔBAT = 37 [range = 46–70] ms) and BAT directly correlated with hematocrit (Spearman’s-ρ = 0.62; p < 0.001). Findings support the feasibility of WM CBF quantification using ASL in SCD participants for appropriately parameterized protocols.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"58 1","pages":"271678X241270283"},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microglia contact cerebral vasculature through gaps between astrocyte endfeet 小胶质细胞通过星形胶质细胞端瓣之间的间隙与脑血管接触

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2024-09-10 DOI: 10.1177/0271678x241280775

Gary P Morris, Catherine G Foster, Brad A Sutherland, Søren Grubb

{"title":"Microglia contact cerebral vasculature through gaps between astrocyte endfeet","authors":"Gary P Morris, Catherine G Foster, Brad A Sutherland, Søren Grubb","doi":"10.1177/0271678x241280775","DOIUrl":"https://doi.org/10.1177/0271678x241280775","url":null,"abstract":"The close spatial relationship between microglia and cerebral blood vessels implicates microglia in vascular development, homeostasis and disease. In this study we used the publicly available Cortical MM^3 electron microscopy dataset to systematically investigate microglial interactions with the vasculature. Our analysis revealed that approximately 20% of microglia formed direct contacts with blood vessels through gaps between adjacent astrocyte endfeet. We termed these contact points “plugs”. Plug-forming microglia exhibited closer proximity to blood vessels than non-plug forming microglia and formed multiple plugs, predominantly near the soma, ranging in surface area from ∼0.01 μm2 to ∼15 μm2. Plugs were enriched at the venule end of the vascular tree and displayed a preference for contacting endothelial cells over pericytes at a ratio of 3:1. In summary, we provide novel insights into the ultrastructural relationship between microglia and the vasculature, laying a foundation for understanding how these contacts contribute to the functional cross-talk between microglia and cells of the vasculature in health and disease.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Refined movement analysis in the Staircase test reveals differential motor deficits in mouse models of stroke 阶梯测试中的精细运动分析表明中风小鼠模型存在不同的运动障碍

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2024-05-15 DOI: 10.1177/0271678x241254718

Matej Skrobot, Rafael De Sa, Josefine Walter, Arend Vogt, Raik Paulat, Janet Lips, Larissa Mosch, Susanne Mueller, Sina Dominiak, Robert Sachdev, Philipp Boehm-Sturm, Ulrich Dirnagl, Matthias Endres, Christoph Harms, Nikolaus Wenger

{"title":"Refined movement analysis in the Staircase test reveals differential motor deficits in mouse models of stroke","authors":"Matej Skrobot, Rafael De Sa, Josefine Walter, Arend Vogt, Raik Paulat, Janet Lips, Larissa Mosch, Susanne Mueller, Sina Dominiak, Robert Sachdev, Philipp Boehm-Sturm, Ulrich Dirnagl, Matthias Endres, Christoph Harms, Nikolaus Wenger","doi":"10.1177/0271678x241254718","DOIUrl":"https://doi.org/10.1177/0271678x241254718","url":null,"abstract":"Accurate assessment of post-stroke deficits is crucial in translational research. Recent advances in machine learning offer precise quantification of rodent motor behavior post-stroke, yet detecting lesion-specific upper extremity deficits remains unclear. Employing proximal middle cerebral artery occlusion (MCAO) and cortical photothrombosis (PT) in mice, we assessed post-stroke impairments via the Staircase test. Lesion locations were identified using 7 T-MRI. Machine learning was applied to reconstruct forepaw kinematic trajectories and feature analysis was achieved with MouseReach, a new data-processing toolbox. Lesion reconstructions pinpointed ischemic centers in the striatum (MCAO) and sensorimotor cortex (PT). Pellet retrieval alterations were observed, but were unrelated to overall stroke volume. Instead, forepaw slips and relative reaching success correlated with increasing cortical lesion size in both models. Striatal lesion size after MCAO was associated with prolonged reach durations that occurred with delayed symptom onset. Further analysis on the impact of selective serotonin reuptake inhibitors in the PT model revealed no clear treatment effects but replicated strong effect sizes of slips for post-stroke deficit detection. In summary, refined movement analysis unveiled specific deficits in two widely-used mouse stroke models, emphasizing the value of deep behavioral profiling in preclinical stroke research to enhance model validity for clinical translation.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141060215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enlarged perivascular spaces in alcohol-related brain damage induced by dyslipidemia 血脂异常诱发酒精相关脑损伤的血管周围空间扩大

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2024-05-03 DOI: 10.1177/0271678x241251570

Han Liu, Lin Meng, Jiuqi Wang, Chi Qin, Renyi Feng, Yongkang Chen, Pei Chen, Qingyong Zhu, Mingming Ma, Junfang Teng, Xuebing Ding

{"title":"Enlarged perivascular spaces in alcohol-related brain damage induced by dyslipidemia","authors":"Han Liu, Lin Meng, Jiuqi Wang, Chi Qin, Renyi Feng, Yongkang Chen, Pei Chen, Qingyong Zhu, Mingming Ma, Junfang Teng, Xuebing Ding","doi":"10.1177/0271678x241251570","DOIUrl":"https://doi.org/10.1177/0271678x241251570","url":null,"abstract":"Perivascular spaces (PVSs) as the anatomical basis of the glymphatic system, are increasingly recognized as potential imaging biomarkers of neurological conditions. However, it is not clear whether enlarged PVSs are associated with alcohol-related brain damage (ARBD). We aimed to investigate the effect of long-term alcohol exposure on dyslipidemia and the glymphatic system in ARBD. We found that patients with ARBD exhibited significantly enlargement of PVSs in the frontal cortex and basal ganglia, as well as a notable increased levels of total cholesterol (TC) and triglycerides (TG). The anatomical changes of the glymphatic drainage system mentioned above were positively associated with TC and TG. To further explore whether enlarged PVSs affects the function of the glymphatic system in ARBD, we constructed long alcohol exposure and high fat diet mice models. The mouse model of long alcohol exposure exhibited increased levels of TC and TG, enlarged PVSs, the loss of aquaporin-4 polarity caused by reactive astrocytes and impaired glymphatic drainage function which ultimately caused cognitive deficits, in a similar way as high fat diet leading to impairment in glymphatic drainage. Our study highlights the contribution of dyslipidemia due to long-term alcohol abuse in the impairment of the glymphatic drainage system.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140827418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Time-domain methods for quantifying dynamic cerebral blood flow autoregulation: Review and recommendations. A white paper from the Cerebrovascular Research Network (CARNet) 量化动态脑血流自动调节的时域方法：回顾与建议。脑血管研究网络（CARNet）白皮书

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2024-05-01 DOI: 10.1177/0271678x241249276

Kyriaki Kostoglou, Felipe Bello-Robles, Patrice Brassard, Max Chacon, Jurgen AHR Claassen, Marek Czosnyka, Jan-Willem Elting, Kun Hu, Lawrence Labrecque, Jia Liu, Vasilis Z Marmarelis, Stephen J Payne, Dae Cheol Shin, David Simpson, Jonathan Smirl, Ronney B Panerai, Georgios D Mitsis

{"title":"Time-domain methods for quantifying dynamic cerebral blood flow autoregulation: Review and recommendations. A white paper from the Cerebrovascular Research Network (CARNet)","authors":"Kyriaki Kostoglou, Felipe Bello-Robles, Patrice Brassard, Max Chacon, Jurgen AHR Claassen, Marek Czosnyka, Jan-Willem Elting, Kun Hu, Lawrence Labrecque, Jia Liu, Vasilis Z Marmarelis, Stephen J Payne, Dae Cheol Shin, David Simpson, Jonathan Smirl, Ronney B Panerai, Georgios D Mitsis","doi":"10.1177/0271678x241249276","DOIUrl":"https://doi.org/10.1177/0271678x241249276","url":null,"abstract":"Cerebral Autoregulation (CA) is an important physiological mechanism stabilizing cerebral blood flow (CBF) in response to changes in cerebral perfusion pressure (CPP). By maintaining an adequate, relatively constant supply of blood flow, CA plays a critical role in brain function. Quantifying CA under different physiological and pathological states is crucial for understanding its implications. This knowledge may serve as a foundation for informed clinical decision-making, particularly in cases where CA may become impaired. The quantification of CA functionality typically involves constructing models that capture the relationship between CPP (or arterial blood pressure) and experimental measures of CBF. Besides describing normal CA function, these models provide a means to detect possible deviations from the latter. In this context, a recent white paper from the Cerebrovascular Research Network focused on Transfer Function Analysis (TFA), which obtains frequency domain estimates of dynamic CA. In the present paper, we consider the use of time-domain techniques as an alternative approach. Due to their increased flexibility, time-domain methods enable the mitigation of measurement/physiological noise and the incorporation of nonlinearities and time variations in CA dynamics. Here, we provide practical recommendations and guidelines to support researchers and clinicians in effectively utilizing these techniques to study CA.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140827419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamic neuroreceptor positron emission tomography in non-anesthetized rats using point source based motion correction: A feasibility study with [11C]ABP688 使用基于点源的运动校正技术对非麻醉大鼠进行动态神经受体正电子发射断层扫描：使用[11C]ABP688的可行性研究

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2024-04-29 DOI: 10.1177/0271678x241239133

Tina Kroll, Alan Miranda, Alexandra Drechsel, Simone Beer, Markus Lang, Alexander Drzezga, Pedro Rosa-Neto, Jeroen Verhaeghe, David Elmenhorst, Andreas Bauer

{"title":"Dynamic neuroreceptor positron emission tomography in non-anesthetized rats using point source based motion correction: A feasibility study with [11C]ABP688","authors":"Tina Kroll, Alan Miranda, Alexandra Drechsel, Simone Beer, Markus Lang, Alexander Drzezga, Pedro Rosa-Neto, Jeroen Verhaeghe, David Elmenhorst, Andreas Bauer","doi":"10.1177/0271678x241239133","DOIUrl":"https://doi.org/10.1177/0271678x241239133","url":null,"abstract":"To prevent motion artifacts in small animal positron emission tomography (PET), animals are routinely scanned under anesthesia or physical restraint. Both may potentially alter metabolism and neurochemistry. This study investigates the feasibility of fully awake acquisition and subsequent absolute quantification of dynamic brain PET data via pharmacokinetic modelling in moving rats using the glutamate 5 receptor radioligand [11C]ABP688 and point source based motion correction. Five male rats underwent three dynamic [11C]ABP688 PET scans: two test-retest awake PET scans and one scan under anesthesia for comparison. Specific radioligand binding was determined via the simplified reference tissue model (reference: cerebellum) and outcome parameters BPND and R1 were evaluated in terms of stability and reproducibility. Test-retest measurements in awake animals gave reliable results with high correlations of BPND (y = 1.08 × −0.2, r = 0.99, p < 0.01) and an acceptable variability (mean over all investigated regions 15.7 ± 2.4%). Regional [11C]ABP688 BPNDs under awake and anesthetized conditions were comparable although in awake scans, absolute radioactive peak uptakes were lower and relative blood flow in terms of R1 was higher. Awake small animal PET with absolute quantification of neuroreceptor availability is technically feasible and reproducible thereby providing a suitable alternative whenever effects of anesthesia are undesirable, e.g. in sleep research.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140827352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endothelial lincRNA-p21 alleviates cerebral ischemia/reperfusion injury by maintaining blood-brain barrier integrity 内皮细胞 lincRNA-p21 通过维持血脑屏障完整性减轻脑缺血再灌注损伤

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2024-04-25 DOI: 10.1177/0271678x241248907

Yun-Hua Zhao, Yu Liang, Kang-Ji Wang, Sheng-Nan Jin, Xiao-Meng Yu, Qian Zhang, Jia-Yi Wei, Hui Liu, Wen-Gang Fang, Wei-Dong Zhao, Yuan Li, Yu-Hua Chen

{"title":"Endothelial lincRNA-p21 alleviates cerebral ischemia/reperfusion injury by maintaining blood-brain barrier integrity","authors":"Yun-Hua Zhao, Yu Liang, Kang-Ji Wang, Sheng-Nan Jin, Xiao-Meng Yu, Qian Zhang, Jia-Yi Wei, Hui Liu, Wen-Gang Fang, Wei-Dong Zhao, Yuan Li, Yu-Hua Chen","doi":"10.1177/0271678x241248907","DOIUrl":"https://doi.org/10.1177/0271678x241248907","url":null,"abstract":"Blood-brain barrier (BBB) disruption is increasingly recognized as an early contributor to the pathophysiology of cerebral ischemia/reperfusion (I/R) injury, and is also a key event in triggering secondary damage to the central nervous system. Recently, long non-coding RNA (lncRNA) have been found to be associated with ischemic stroke. However, the roles of lncRNA in BBB homeostasis remain largely unknown. Here, we report that long intergenic non-coding RNA-p21 (lincRNA-p21) was the most significantly down-regulated lncRNA in human brain microvascular endothelial cells (HBMECs) after oxygen and glucose deprivation/reoxygenation (OGD/R) treatment among candidate lncRNA, which were both sensitive to hypoxia and involved in atherosclerosis. Exogenous brain-endothelium-specific overexpression of lincRNA-p21 could alleviate BBB disruption, diminish infarction volume and attenuate motor function deficits in middle cerebral artery occlusion/reperfusion (MCAO/R) mice. Further results showed that lincRNA-p21 was critical to maintain BBB integrity by inhibiting the degradation of junction proteins under MCAO/R and OGD/R conditions. Specifically, lincRNA-p21 could inhibit autophagy-dependent degradation of occludin by activating PI3K/AKT/mTOR signaling pathway. Besides, lincRNA-p21 could inhibit VE-cadherin degradation by binding with miR-101-3p. Together, we identify that lincRNA-p21 is critical for BBB integrity maintenance, and endothelial lincRNA-p21 overexpression could alleviate cerebral I/R injury in mice, pointing to a potential strategy to treat cerebral I/R injury.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"99 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140798079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An update on stem cell therapy for stroke patients: Where are we now? 中风患者干细胞疗法的最新进展：我们现在在哪里？

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2024-04-19 DOI: 10.1177/0271678x241227022

Jonah Gordon, Cesar V Borlongan

{"title":"An update on stem cell therapy for stroke patients: Where are we now?","authors":"Jonah Gordon, Cesar V Borlongan","doi":"10.1177/0271678x241227022","DOIUrl":"https://doi.org/10.1177/0271678x241227022","url":null,"abstract":"With a foundation built upon initial work from the 1980s demonstrating graft viability in cerebral ischemia, stem cell transplantation has shown immense promise in promoting survival, enhancing neuroprotection and inducing neuroregeneration, while mitigating both histological and behavioral deficits that frequently accompany ischemic stroke. These findings have led to a number of clinical trials that have thoroughly supported a strong safety profile for stem cell therapy in patients but have generated variable efficacy. As preclinical evidence continues to expand through the investigation of new cell lines and optimization of stem cell delivery, it remains critical for translational models to adhere to the protocols established through basic scientific research. With the recent shift in approach towards utilization of stem cells as a conjunctive therapy alongside standard thrombolytic treatments, key issues including timing, route of administration, and stem cell type must each be appropriately translated from the laboratory in order to resolve the question of stem cell efficacy for cerebral ischemia that ultimately will enhance therapeutics for stroke patients towards improving quality of life.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140630543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0