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

A-kinase anchor protein 12 promotes oligodendrogenesis and cognitive recovery in carbon monoxide therapy for traumatic brain injury. A-激酶锚定蛋白12在一氧化碳治疗创伤性脑损伤的过程中促进少突生成和认知能力恢复。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-01 Epub Date: 2025-01-25 DOI: 10.1177/0271678X251314371

Yoon Kyung Choi, Takakuni Maki, Anna C Liang, Kazuhide Hayakawa, Seong-Ho Koh, Young-Myeong Kim, Michael J Whalen, Ji Hae Seo, Josephine Lok, Irwin H Gelman, Kyu-Won Kim, Eng H Lo, Ken Arai

{"title":"A-kinase anchor protein 12 promotes oligodendrogenesis and cognitive recovery in carbon monoxide therapy for traumatic brain injury.","authors":"Yoon Kyung Choi, Takakuni Maki, Anna C Liang, Kazuhide Hayakawa, Seong-Ho Koh, Young-Myeong Kim, Michael J Whalen, Ji Hae Seo, Josephine Lok, Irwin H Gelman, Kyu-Won Kim, Eng H Lo, Ken Arai","doi":"10.1177/0271678X251314371","DOIUrl":"10.1177/0271678X251314371","url":null,"abstract":"Therapeutic drug development for central nervous system injuries, such as traumatic brain injury (TBI), presents significant challenges. TBI results in primary mechanical damage followed by secondary injury, leading to cognitive dysfunction and memory loss. Our recent study demonstrated the potential of carbon monoxide-releasing molecules (CORMs) to improve TBI recovery by enhancing neurogenesis. However, a comprehensive TBI recovery strategy requires not only neurogenesis but also oligodendrogenesis. In this study, we elucidate the critical role of A-kinase anchor protein 12 (AKAP12), a scaffolding protein predominantly expressed by intact pericytes, in oligodendrocyte regeneration during CO therapy for TBI. CORM treatment increased AKAP12 expression, which enhanced myelin intensity and mitigated TBI-induced oligodendrocyte loss. In addition, CO promotes the generation of new oligodendrocytes, a process that is impaired by AKAP12 deficiency. Notably, even after TBI, cognitive function was restored in wild-type mice following CORM treatment, but this effect was absent in Akap12 knockout mice. These findings highlight the importance of CO-induced AKAP12 upregulation, particularly in pericytes, in supporting oligodendrogenesis and cognitive recovery after TBI. Understanding these mechanisms holds promise for the development of targeted therapies to address TBI-associated impairments.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1180-1190"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038940","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

Glucocorticoid signaling mediates lymphopoiesis impairment after cardiac arrest in mice. 糖皮质激素信号介导小鼠心脏骤停后的淋巴系统损伤。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-01 Epub Date: 2025-01-21 DOI: 10.1177/0271678X251314321

Ángela Del Águila, Lihong Dang, Ran Zhang, Jin Zhang, Ata Ur Rehman, Feng Xu, Ashis Dhar, Xiao-Ping Zhong, Huaxin Sheng, Wei Yang

{"title":"Glucocorticoid signaling mediates lymphopoiesis impairment after cardiac arrest in mice.","authors":"Ángela Del Águila, Lihong Dang, Ran Zhang, Jin Zhang, Ata Ur Rehman, Feng Xu, Ashis Dhar, Xiao-Ping Zhong, Huaxin Sheng, Wei Yang","doi":"10.1177/0271678X251314321","DOIUrl":"10.1177/0271678X251314321","url":null,"abstract":"Cardiac arrest (CA) is a life-threatening condition that requires immediate medical attention. Considerable advances in resuscitation have led to an increasing number of patients who survive the initial arrest event. However, among this growing patient population, morbidity and mortality rates remain strikingly high. This has been attributed to post-CA syndrome of which an imbalanced immune response is a crucial component. Using a murine CA model, we have shown that a profound immunosuppressive phase, characterized by severe lymphopenia, ensues following the initial pro-inflammatory response after CA. In the current study, we found that T and B lymphopoiesis was greatly impaired, as evidenced by the rapid and marked depletion of double-positive T cells and pre-B cells in the thymus and bone marrow, respectively. Our data then demonstrated that pharmacologic suppression of glucocorticoid signaling after CA significantly attenuated lymphopoiesis impairment, thereby mitigating post-CA lymphopenia. Lastly, we showed that specific deletion of the glucocorticoid receptor in T or B cells largely prevented the CA-induced depletion of immature lymphocyte populations in the thymus or bone marrow, respectively. Together, our findings indicate that glucocorticoid signaling mediates post-CA impairment of lymphopoiesis, a key contributor to post-CA immunosuppression.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1166-1179"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006237","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

Circulating molecules reflect imaging biomarkers of hemorrhage in cerebral cavernous malformations. 循环分子反映脑海绵状畸形出血的成像生物标志物。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-01 Epub Date: 2025-01-20 DOI: 10.1177/0271678X251314366

Stephanie F Hage, Dehua E Bi, Serena Kinkade, Diana Vera Cruz, Abhinav Srinath, Aditya Jhaveri, Sharbel Romanos, Akash Bindal, Rhonda Lightle, Jessica C Little, Robert Shenkar, Roberto J Alcazar-Felix, Justine Lee, Agnieszka Stadnik, Ashley Sidebottom, Timothy J Carroll, Yuan Ji, Janne Koskimaki, Sean P Polster, Romuald Girard, Issam A Awad

{"title":"Circulating molecules reflect imaging biomarkers of hemorrhage in cerebral cavernous malformations.","authors":"Stephanie F Hage, Dehua E Bi, Serena Kinkade, Diana Vera Cruz, Abhinav Srinath, Aditya Jhaveri, Sharbel Romanos, Akash Bindal, Rhonda Lightle, Jessica C Little, Robert Shenkar, Roberto J Alcazar-Felix, Justine Lee, Agnieszka Stadnik, Ashley Sidebottom, Timothy J Carroll, Yuan Ji, Janne Koskimaki, Sean P Polster, Romuald Girard, Issam A Awad","doi":"10.1177/0271678X251314366","DOIUrl":"10.1177/0271678X251314366","url":null,"abstract":"Increases in mean lesional iron content by quantitative susceptibility mapping (QSM) by ≥6% and/or vascular permeability by dynamic contrast enhanced quantitative perfusion (DCEQP) by ≥40% on MRI have been associated with new symptomatic hemorrhage (SH) in cerebral cavernous malformations (CCMs). It is not known if plasma biomarkers can reflect these changes within the lesion proper. This cohort study enrolled 46 CCM patients with SH in the prior year. Plasma samples, QSM and DCEQP were simultaneously acquired at the beginning and end of 60 one-year epochs of prospective follow-up. Plasma levels of 16 proteins and 12 metabolites linked to CCM hemorrhage were assessed by enzyme-linked immunosorbent assay and liquid-chromatography mass spectrometry, respectively. A weighted model combining the percent changes in plasma levels in roundabout guidance receptor-4, cluster of differentiation 14, thrombomodulin and acetyl-L-carnitine reflected a mean increase in QSM ≥ 6% (97.2% and 100% specificity/sensitivity, p = 3.1 × 10-13). A weighted combination of percent changes in plasma levels of endoglin, pipecolic acid, arachidonic acid and hypoxanthine correlated with an increase in mean DCEQP ≥40% (99.6% specificity and 100% sensitivity, p = 4.1 × 10-17). This is a first report linking with great accuracy changes of circulating molecules to imaging changes reflecting new SH during prospective follow-up of CCMs.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1153-1165"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006228","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

Collateral blood vessels in stroke and ischemic disease: Formation, physiology, rarefaction, remodeling. 中风和缺血性疾病的侧支血管：形成、生理、稀释、重塑。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-01 Epub Date: 2025-03-12 DOI: 10.1177/0271678X251322378

James E Faber

{"title":"Collateral blood vessels in stroke and ischemic disease: Formation, physiology, rarefaction, remodeling.","authors":"James E Faber","doi":"10.1177/0271678X251322378","DOIUrl":"10.1177/0271678X251322378","url":null,"abstract":"Collateral blood vessels are unique, naturally occurring endogenous bypass vessels that provide alternative pathways for oxygen delivery in obstructive arterial conditions and diseases. Surprisingly however, the capacity of the collateral circulation to provide protection varies greatly among individuals, resulting in a significant fraction having poor collateral circulation in their tissues. We recently reviewed evidence that the presence of naturally-occurring polymorphisms in genes that determine the number and diameter of collaterals that form during development (ie, genetic background), is a major contributor to this variation. The purpose of this review is to summarize current understanding of the other determinants of collateral blood flow, drawing on both animal and human studies. These include the level of smooth muscle tone in collaterals, hemodynamic forces, how collaterals form during development (collaterogenesis), de novo formation of additional new collaterals during adulthood, loss of collaterals with aging and cardiovascular risk factor presence (rarefaction), and collateral remodeling (structural lumen enlargement). We also review emerging evidence that collaterals not only provide protection in ischemic conditions but may also serve a physiological function in healthy individuals. Primary focus is on studies conducted in brain, however relevant findings in other tissues are also reviewed, as are questions for future investigation.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1007-1030"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605098","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

Isoform-selective and non-selective rho-kinase inhibitors do not affect collagenase-induced intracerebral hemorrhage outcomes in mice: Influence of sex and circadian cycle. 同种异构体选择性和非选择性rho激酶抑制剂不影响小鼠胶原酶诱导的脑出血结果：性别和昼夜周期的影响

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-01 Epub Date: 2025-01-07 DOI: 10.1177/0271678X241312010

Takahiko Imai, Andreia Morais, Tao Qin, Yuichi Sasaki, Taylan Erdogan, Lisa McKerracher, Cenk Ayata

{"title":"Isoform-selective and non-selective rho-kinase inhibitors do not affect collagenase-induced intracerebral hemorrhage outcomes in mice: Influence of sex and circadian cycle.","authors":"Takahiko Imai, Andreia Morais, Tao Qin, Yuichi Sasaki, Taylan Erdogan, Lisa McKerracher, Cenk Ayata","doi":"10.1177/0271678X241312010","DOIUrl":"10.1177/0271678X241312010","url":null,"abstract":"Rho-associated protein kinase (ROCK) inhibitors are therapeutic candidates in ischemic stroke and subarachnoid hemorrhage. However, their efficacy in intracerebral hemorrhage (ICH) is unknown. Here, we tested the efficacy of fasudil (10 mg/kg), an isoform-nonselective ROCK inhibitor, and NRL-1049 (10 mg/kg), a novel inhibitor with 43-fold higher selectivity for ROCK2 isoform compared with ROCK1, in a collagenase-induced ICH model in mice. Both short (1-3 days) and prolonged (14 days) therapeutic paradigms were tested using robust sample sizes in both males and females and in active and inactive circadian stages. Outcome readouts included weight loss, mortality, hematoma volume, hemispheric swelling, brain water content, BBB permeability to large molecules, and sensorimotor and cognitive function. We found the treatments safe but not efficacious in improving the hematoma volume, BBB disruption, or neurological deficits in this collagenase-induced ICH model. Intriguingly, however, induction of ICH during the active circadian stage was associated with worse tissue and behavioral outcomes compared with the inactive stage.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1191-1202"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949615","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

Glutamine metabolism is systemically different between primary and induced pluripotent stem cell-derived brain microvascular endothelial cells. 谷氨酰胺代谢在原代和诱导多能干细胞衍生的脑微血管内皮细胞之间存在系统性差异。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-01 Epub Date: 2025-01-07 DOI: 10.1177/0271678X241310729

Callie M Weber, Bilal Moiz, Marzyeh Kheradmand, Arielle Scott, Claire Kettula, Brooke Wunderler, Viviana Alpízar Vargas, Alisa Morss Clyne

{"title":"Glutamine metabolism is systemically different between primary and induced pluripotent stem cell-derived brain microvascular endothelial cells.","authors":"Callie M Weber, Bilal Moiz, Marzyeh Kheradmand, Arielle Scott, Claire Kettula, Brooke Wunderler, Viviana Alpízar Vargas, Alisa Morss Clyne","doi":"10.1177/0271678X241310729","DOIUrl":"10.1177/0271678X241310729","url":null,"abstract":"Human primary (hpBMEC) and induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial-like cells (hiBMEC) are interchangeably used in blood-brain barrier models to study neurological diseases and drug delivery. Both hpBMEC and hiBMEC use glutamine as a source of carbon and nitrogen to produce metabolites and build proteins essential to cell function and communication. We used metabolomic, transcriptomic, and computational methods to examine how hpBMEC and hiBMEC metabolize glutamine, which may impact their utility in modeling the blood-brain barrier. We found that glutamine metabolism was systemically different between the two cell types. hpBMEC had a higher metabolic rate and produced more glutamate and GABA, while hiBMEC rerouted glutamine to produce more glutathione, fatty acids, and asparagine. Higher glutathione production in hiBMEC correlated with higher oxidative stress compared to hpBMEC. α-ketoglutarate (α-KG) supplementation increased glutamate secretion from hiBMEC to match that of hpBMEC; however, α-KG also decreased hiBMEC glycolytic rate. These fundamental metabolic differences between BMEC types may impact in vitro blood-brain barrier model function, particularly communication between BMEC and surrounding cells, and emphasize the importance of evaluating the metabolic impacts of iPSC-derived cells in disease models.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1082-1099"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949614","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

Non-invasive [¹⁵O]H₂O PET measurements of cerebral perfusion and cerebrovascular reactivity using an additional heart scan. 无创[15O]H2O PET测量脑灌注和脑血管反应性使用额外的心脏扫描。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-01 Epub Date: 2025-01-20 DOI: 10.1177/0271678X251313743

Mathias Jacobsen Bach, Mia E Larsen, Amanda O Kellberg, Alexander C Henriksen, Stefan Fuglsang, Inge Lise Rasmussen, Markus Nowak Lonsdale, Mark Lubberink, Lisbeth Marner

{"title":"Non-invasive [15O]H2O PET measurements of cerebral perfusion and cerebrovascular reactivity using an additional heart scan.","authors":"Mathias Jacobsen Bach, Mia E Larsen, Amanda O Kellberg, Alexander C Henriksen, Stefan Fuglsang, Inge Lise Rasmussen, Markus Nowak Lonsdale, Mark Lubberink, Lisbeth Marner","doi":"10.1177/0271678X251313743","DOIUrl":"10.1177/0271678X251313743","url":null,"abstract":"Obtaining the arterial input function (AIF) is essential for quantitative regional cerebral perfusion (rCBF) measurements using [15O]H2O PET. However, arterial blood sampling is invasive and complicates the scanning procedure. We propose a new non-invasive dual scan technique with an image derived input function (IDIF) from an additional heart scan. Six patients and two healthy subjects underwent [15O]H2O PET imaging of 1) heart and brain during baseline, and 2) heart and brain after infusion of acetazolamide. The IDIF was extracted from the left ventricle of the heart and compared to the AIF. The rCBF was compared for six bilateral cortical regions. AIFs and IDIFs showed strong agreement. rCBF with AIF and IDIF showed strong correlation for both baseline rCBF (R2 = 0.99, slope = 0.89 CI: [0.87; 0.91], p < 0.0001) and acetazolamide rCBF (R2 = 0.98, slope = 0.93, CI:[0.90;0.97], p < 0.0001) but showed a positive bias of 0.047 mL/(g·min) [-0.025; +0.119] for baseline and 0.024 [-1.04, +1.53] mL/(g·min) for acetazolamide. In conclusion, the invasive arterial cannulation can be replaced by an additional scan of the heart with a minor bias of rCBF estimation. The method is applicable to all scanner systems.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1144-1152"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006240","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 high fat diet-induced cerebrovascular remodeling impairs recovery of blood flow after cerebral ischemia in mice. 慢性高脂饮食诱导的脑血管重塑损害小鼠脑缺血后血流恢复。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-01 Epub Date: 2025-01-17 DOI: 10.1177/0271678X251313723

Jun Li, Naidi Sun, Song Hu, Zhiyi Zuo

{"title":"Chronic high fat diet-induced cerebrovascular remodeling impairs recovery of blood flow after cerebral ischemia in mice.","authors":"Jun Li, Naidi Sun, Song Hu, Zhiyi Zuo","doi":"10.1177/0271678X251313723","DOIUrl":"10.1177/0271678X251313723","url":null,"abstract":"Obesity and associated metabolic disturbances worsen brain ischemia outcome. High fat diet (HFD)-fed mice are obese and have cerebrovascular remodeling and worsened brain ischemia outcome. We determined whether HFD-induced cerebrovascular remodeling impaired reperfusion to the ischemic penumbra. Six-week-old C57BL/6J or matrix metalloprotease-9 knockout (MMP-9-/-) mice were on HFD or regular diet (RD) for 12 to 14 months before a 60-min left middle cerebral arterial occlusion (MCAO). Photoacoustic microscopy was performed at left cerebral frontal cortex. HFD increased cerebrovascular density and tortuosity in C57BL/6J mice but not in MMP-9-/- mice. Blood flow to the ischemic penumbra slowly recovered but did not reach the baseline 2 h after MCAO in RD-fed mice. Oxygen extraction fraction was increased to maintain cerebral metabolic rate of oxygen (CMRO2) throughout brain ischemia and reperfusion period. This blood flow recovery was worsened in HFD-fed mice, leading to decreased CMRO2. MMP-9-/- attenuated these HFD effects. HFD increased MMP-9 activity and interleukin 1β. Pyrrolidine dithiocarbamate, an anti-inflammatory agent, abolished the HFD effects. Interleukin 1β increased MMP-9 activity. In summary, HFD induces cerebrovascular remodeling, leading to worsened recovery of blood supply to the ischemic penumbra to contribute to poor outcome after brain ischemia. Neuroinflammation may activate MMP-9 in HFD-fed mice.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1116-1129"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006220","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

Systematic review and meta-analysis of transcranial doppler biomarkers for the prediction of delayed cerebral ischemia following subarachnoid hemorrhage. 经颅多普勒生物标志物预测蛛网膜下腔出血后迟发性脑缺血的系统回顾和meta分析。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-01 Epub Date: 2025-03-20 DOI: 10.1177/0271678X251313746

Hanna Schenck, Céline van Craenenbroeck, Sander van Kuijk, Erik Gommer, Michael Veldeman, Yasin Temel, Marcel Aries, Werner Mess, Roel Haeren

{"title":"Systematic review and meta-analysis of transcranial doppler biomarkers for the prediction of delayed cerebral ischemia following subarachnoid hemorrhage.","authors":"Hanna Schenck, Céline van Craenenbroeck, Sander van Kuijk, Erik Gommer, Michael Veldeman, Yasin Temel, Marcel Aries, Werner Mess, Roel Haeren","doi":"10.1177/0271678X251313746","DOIUrl":"10.1177/0271678X251313746","url":null,"abstract":"Delayed cerebral ischemia (DCI) following an aneurysmal subarachnoid hemorrhage (aSAH) significantly impacts mortality, morbidity, and healthcare costs. This study assessed the diagnostic accuracy of Transcranial Doppler (TCD)-derived biomarkers for predicting DCI via a systematic review and meta-analysis. Included studies had to correctly define DCI and report data on sensitivity, specificity, positive predictive value, and negative predictive value. Univariate or bivariate analyses with a random effects model were used, and risk of bias was evaluated with the Quality Assessment of Diagnostic Accuracy Studies. From 23 eligible articles (n = 2371 patients), three biomarker categories were identified: cerebral blood flow velocities (CBFV), cerebral autoregulation, and microembolic signals (MES). The highest sensitivity (0.86, 95% CI 0.71-0.94) and specificity (0.75, 95% CI 0.52-0.94) for DCI prediction were achieved with a mean CBFV of 120 cm/s combined with a Lindegaard ratio. The transient hyperemic response test showed the best performance among autoregulatory biomarkers with a sensitivity of 0.88, (95% CI 0.54-0.98) and specificity of 0.82 (95% CI 0.52-0.94). MES were less effective predictors. Combining CBFV with autoregulatory biomarkers enhanced TCD's predictive value. High heterogeneity and risk of bias were noted, indicating the need for a standardized TCD approach for improved DCI evaluation.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1031-1047"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663604","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

Progression of experimental autoimmune encephalomyelitis in mice and neutrophil-mediated blood-brain barrier dysfunction requires non-muscle myosin light chain kinase. 小鼠实验性自身免疫性脑脊髓炎的进展和中性粒细胞介导的血脑屏障功能障碍需要非肌球蛋白轻链激酶。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-01 Epub Date: 2025-02-07 DOI: 10.1177/0271678X251318620

Richard S Beard, Brian A Hoettels, Jessica M McAllister, Jamie E Meegan, Travis S Wertz, Desiree A Self, Dylan E Hrkach, Daniel Greiner, Kristina Chapman, Nuria Villalba, Xiaoyuan Yang, Byeong J Cha, Cheryl L Jorcyk, Julia T Oxford, Mack H Wu, Sarah Y Yuan

{"title":"Progression of experimental autoimmune encephalomyelitis in mice and neutrophil-mediated blood-brain barrier dysfunction requires non-muscle myosin light chain kinase.","authors":"Richard S Beard, Brian A Hoettels, Jessica M McAllister, Jamie E Meegan, Travis S Wertz, Desiree A Self, Dylan E Hrkach, Daniel Greiner, Kristina Chapman, Nuria Villalba, Xiaoyuan Yang, Byeong J Cha, Cheryl L Jorcyk, Julia T Oxford, Mack H Wu, Sarah Y Yuan","doi":"10.1177/0271678X251318620","DOIUrl":"10.1177/0271678X251318620","url":null,"abstract":"Blood-brain barrier (BBB) dysfunction occurs in numerous central nervous system disorders. Unfortunately, a limited understanding of the mechanisms governing barrier function hinders the identification and assessment of BBB-targeted therapies. Previously, we found that non-muscle myosin light chain kinase (nmMLCK) negatively regulates the tight junction protein claudin-5 in brain microvascular endothelial cells (BMVECs) under inflammatory conditions. Here, we used complementary animal and primary cell co-culture models to further investigate nmMLCK and claudin-5 during neuroinflammation. We found that nmMLCK-knockout mice resisted experimental autoimmune encephalomyelitis (EAE), including paralysis, demyelination, neutrophil infiltration, and BBB dysfunction. However, transiently silencing claudin-5 culminated in a fulminant disease course. In parallel, we found that neutrophil-secreted factors triggered a biphasic loss in the barrier quality of wild-type BMVEC monolayers, plus pronounced neutrophil migration during the second phase. Conversely, nmMLCK-knockout monolayers resisted barrier dysfunction and neutrophil migration. Lastly, we found an inverse relationship between claudin-5 expression in BMVECs and neutrophil migration. Overall, our findings support a pathogenic role for nmMLCK in BMVECs during EAE that includes BBB dysfunction and neutrophil infiltration, reveal that claudin-5 contributes to the immune barrier properties of BMVECs, and underscore the harmful effects of claudin-5 loss during neuroinflammation.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1203-1220"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364852","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}

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