{"title":"Neurovascular coupling is preserved in the cerebral cortex of diabetic mice: A longitudinal study.","authors":"Pei-Pei Chiang, Amy R Nippert, Eric A Newman","doi":"10.1177/0271678X251377575","DOIUrl":"10.1177/0271678X251377575","url":null,"abstract":"<p><p>Neurovascular coupling (NVC), which mediates transient increases in blood flow to increased neuronal activity, is markedly reduced in the retinas of diabetic patients and in animal models of diabetes. It is unclear, however, whether NVC is similarly reduced in the diabetic brain, as previous studies have yielded conflicting results. We investigated this question by simultaneously monitoring the responses of neurons and adjacent penetrating arterioles to whisker stimulation in the Akita mouse model of type 1 diabetes. We found that NVC, as quantified by two independent analytical techniques, remained constant in Akita mice as diabetes progressed and did not differ from aged-matched control mice. Although NVC, as measured by peak vascular dilation, remained constant, the dilation was more prolonged in 27-33 compared to 11-20 weeks of age (WOA) Akita mice, leading to an enhancement of the blood flow increase. NVC remained constant in control mice between age groups and the basal diameter of penetrating arterioles in both control and Akita mice did not vary between 11 and 33 WOA.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251377575"},"PeriodicalIF":4.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marin Radmilović, Helena Justić, Anja Barić, Martina Ratko, Iva Šimunić, Zoran Vatavuk, Aleksandra Dugandžić, Marina Dobrivojević Radmilović
{"title":"Bradykinin type 2 receptor deficiency alters vascular endothelial growth factor and atrial natriuretic peptide levels in early-stage diabetic retinopathy.","authors":"Marin Radmilović, Helena Justić, Anja Barić, Martina Ratko, Iva Šimunić, Zoran Vatavuk, Aleksandra Dugandžić, Marina Dobrivojević Radmilović","doi":"10.1177/0271678X251377570","DOIUrl":"10.1177/0271678X251377570","url":null,"abstract":"<p><p>Diabetic retinopathy is a leading cause of visual impairment among working-age adults. Given the multiple pathophysiologic functions of bradykinin and its links to vascular endothelial growth factor (VEGF) and atrial natriuretic peptide (ANP) signaling, we hypothesized their interconnected involvement in the development of retinal vascular permeability in early-stage diabetic retinopathy. Diabetic mice, bradykinin type 2 receptor (B2R) knock-out diabetic mice, and their non-diabetic controls underwent magnetic resonance imaging, fluorescein angiography, vascular permeability measurements, retinal ELISA, Western blot, qPCR, and immunohistochemistry, glycemic assessments, and evaluation of intraocular and blood pressure. Diabetes upregulated B2R expression without altering retinal bradykinin levels. B2R deficiency in diabetic mice unexpectedly exacerbated vascular permeability but ameliorated retinal thinning and ganglion cell loss. B2R-deficient animals had decreased VEGF and VEGF receptor-2 levels, despite increased gene expression, indicating a regulatory effect on protein synthesis. Both diabetes and B2R deficiency, especially the latter, increased ANP and guanylyl cyclase/natriuretic peptide receptor-A levels and their gene expression. This study provides new insights into the interplay between bradykinin, VEGF, and ANP in diabetic retinopathy. It highlights a regulatory role of B2R in VEGF and ANP signaling, suggesting targets for future research on vascular permeability and neuroprotection in early-stage diabetic retinopathy.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251377570"},"PeriodicalIF":4.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"G6PD deficiency is implicated in Circle of Willis variants in stroke patients and impairs brain vasculature in zebrafish.","authors":"Yuangui Cai, Jianle Li, Yicong Chen, Zilin Ou, Jiating Wei, Xiya Long, Zhiyi Xiong, Miaoxian Yang, Yingxin He, Hailin Yan, Tingna Zhu, Jinsheng Zeng","doi":"10.1177/0271678X251377678","DOIUrl":"10.1177/0271678X251377678","url":null,"abstract":"<p><p>Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common hereditary enzyme defect in the world, may be involved in cerebrovascular abnormalities suggested by clinical research. However, whether and how G6PD deficiency impairs cerebral vasculature is poorly understood. We therefore aimed at determining the role of G6PD in brain vasculature. By evaluating cerebrovascular imaging data from stroke patients, we found patients with G6PD deficiency exhibited greater morphological variability in the circle of Willis (CoW) with reduced frequency of the anterior communicating artery, bilateral A1 segments, but a higher incidence of fetal posterior cerebral artery (fPCA). To further confirm G6PD deficiency was associated with cerebrovascular abnormalities, we used pharmacological inhibitor to suppress G6PD activity in zebrafish embryos and utilized CRISPR/Cas9 technology to generate <i>g6pd</i> homozygous knockout and endothelial cell-specific knockout zebrafish lines. We found all of these models demonstrated varying degrees of cerebrovascular morphological abnormalities and impairment of cerebrovascular angiogenesis. Transcriptomic data analysis and in vitro experiments further elucidated that G6PD deficiency led to dysfunctional angiogenic response and induced apoptosis. Altogether, we first demonstrated that G6PD deficiency may be associated with CoW variants in stroke patients and impairing cerebrovascular morphology and angiogenesis during zebrafish development.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251377678"},"PeriodicalIF":4.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between different bilirubin subtypes and clinical outcomes in acute ischemic stroke patients undergoing mechanical thrombectomy: A retrospective cohort study.","authors":"Hongye Xu, Lijun Wang, Li Xu, Xiaoxi Zhang, Hongyu Ma, Jianqiang Fan, Longjuan Yu, He Li, Hanchen Liu, Hongjian Shen, Tianxiang Gao, Yu Gao, Wen Yin, Rundong Chen, Yu Zhou, Zhenwei Wen, Weilong Hua, Lei Zhang, Yongxin Zhang, Yongwei Zhang, Jianmin Liu, Pengfei Xing, Zifu Li, Pengfei Yang","doi":"10.1177/0271678X251378298","DOIUrl":"10.1177/0271678X251378298","url":null,"abstract":"<p><p>The association between serum bilirubin levels and clinical outcomes in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy (MT) remains elusive, warranting further investigation. This retrospective cohort study encompassed 787 AIS patients who underwent MT between January 2018 and December 2022. Baseline serum levels of direct bilirubin (DBIL), indirect bilirubin (IBIL), and total bilirubin (TBIL) were documented. Adverse clinical outcomes comprised any intracranial hemorrhage (ICH) within 72 h, symptomatic intracranial hemorrhage, stroke-associated pneumonia (SAP), early neurological deterioration, 3-month poor functional outcome, and 3-month mortality. The findings revealed that DBIL and TBIL levels exhibited positive correlations with the incidence of SAP, ICH, and 3-month poor functional outcome. IBIL levels demonstrated a positive association with ICH occurrence. Notably, DBIL tends to exhibite superior predictive value for adverse outcomes compared to IBIL and TBIL. In conclusion, baseline serum bilirubin could as a potential biomarker for adverse clinical outcomes in AIS patients undergoing MT, pending further validation.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251378298"},"PeriodicalIF":4.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jordan U Hanania, Connor Wj Bevington, Ju-Chieh Kevin Cheng, Dongning Su, Alexandra Pavel, A Jon Stoessl, Vesna Sossi
{"title":"A generalized framework for <i>in vivo</i> detection of dopamine release using positron emission tomography.","authors":"Jordan U Hanania, Connor Wj Bevington, Ju-Chieh Kevin Cheng, Dongning Su, Alexandra Pavel, A Jon Stoessl, Vesna Sossi","doi":"10.1177/0271678X251362958","DOIUrl":"10.1177/0271678X251362958","url":null,"abstract":"<p><p>Voxel-level detection of task-induced striatal dopamine (DA) release in humans is achievable with dynamic PET imaging, enabling complex studies of motor, cognitive, and reward tasks. We previously introduced a data-driven methodology termed Residual Space Detection (RSD), which improved detection of low-amplitude DA release, however its applicability was limited to detection of low-amplitude and/or localized effects. Here, we generalize RSD to broader DA release scenarios by introducing a novel model-based baseline time-activity curve prediction method in combination with non-local-means clustering (RSD-Hybrid-IMRTM). In simulations, RSD-Hybrid-IMRTM outperforms our previous methodology for detecting global striatal DA release, improving absolute detection sensitivity by 18% at 5% false positive rate, while also demonstrating the ability to track the magnitude of task-induced changes in synaptic DA concentrations in a noise-robust manner. As a proof of principle, we apply RSD-Hybrid-IMRTM to healthy controls and Parkinson's disease subjects undergoing finger and foot tapping tasks. Results reveal expected group differences in parametric maps, parameter magnitudes, and functional segregation, demonstrating RSD-Hybrid-IMRTM's utility for investigating neurotransmission in human cohorts.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251362958"},"PeriodicalIF":4.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mudasir Maqbool, Daniel Gündel, Jeih-San Liow, Jinsoo Hong, Paul A Parcon, Raven Cureton, Matilah T Pamie-George, Adrian E Jenson, Shawn Wu, Ioline D Henter, Sami S Zogbhi, Victor W Pike, Rareş-Petru Moldovan, Robert B Innis
{"title":"Evaluation of deuterated [<sup>18</sup>F]JHU94620 for imaging cannabinoid type 2 receptors in rodent and monkey brain.","authors":"Mudasir Maqbool, Daniel Gündel, Jeih-San Liow, Jinsoo Hong, Paul A Parcon, Raven Cureton, Matilah T Pamie-George, Adrian E Jenson, Shawn Wu, Ioline D Henter, Sami S Zogbhi, Victor W Pike, Rareş-Petru Moldovan, Robert B Innis","doi":"10.1177/0271678X251371377","DOIUrl":"10.1177/0271678X251371377","url":null,"abstract":"<p><p>PET imaging of cannabinoid type-2 receptors (CB2Rs) in the healthy brain remains challenging due to low receptor density and the unavailability of radiotracers with high affinity and selectivity. Because some carbon-deuterium bonds are less susceptible than carbon-proton bonds to enzymatic cleavage, deuteration of [<sup>18</sup>F]JHU94620 was pursued to potentially slow its metabolism. This study: (1) evaluated the sensitivity of a heavily deuterated version of the agonist [<sup>18</sup>F]JHU94620 ([<sup>18</sup>F]JHU94620-<i>d</i><sub>8</sub>) to detect brain CB2Rs in healthy Sprague-Dawley rats and monkeys and in a rat model of inflammation; (2) assessed the metabolic stability of [<sup>18</sup>F]JHU94620 and [<sup>18</sup>F]JHU94620-<i>d</i><sub>8</sub> in whole blood, plasma, and brain of control (FVB) mice and in the whole blood and plasma of monkeys; and (3) investigated the efflux transporter substrate liability of [<sup>18</sup>F]JHU94620<i>-d</i><sub>8</sub>. Deuteration of [<sup>18</sup>F]JHU94620 did not significantly affect its uptake in the brains of FVB mice, Sprague-Dawley rats, or monkeys, nor did it affect metabolic stability, except in FVB mice. [<sup>18</sup>F]JHU94620-<i>d</i><sub>8</sub> was also found to be a moderate substrate for efflux transporters in monkeys but not in mice. The sensitivity of [<sup>18</sup>F]JHU94620-<i>d</i><sub>8</sub> was inadequate to detect the low density of CB2Rs that are in the agonist-preferring state in the brain.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251371377"},"PeriodicalIF":4.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neurological recovery after ICH is mediated by the aryl hydrocarbon receptor-bilirubin interplay through improved erythrophagocytosis.","authors":"Xiurong Zhao, Shun-Ming Ting, Guanghua Sun, Jaroslaw Aronowski","doi":"10.1177/0271678X251371375","DOIUrl":"10.1177/0271678X251371375","url":null,"abstract":"<p><p>Hematoma clearance after ICH is a pro-hemostatic process aiming at repair/recovery and is achieved through microglia/macrophages (MMΦ)-mediated erythrophagocytosis. Upon the engulfment of masses of erythrocytes and toxic hemolysis products, hemoglobin and heme, phagocytes convert them to bilirubin (BrB). Bilirubin is essentially not soluble in water and when overproduced, it precipitates within the cell causing injury. Thus, keeping bilirubin soluble and at a low intracellular level is needed for proper function of MMΦ. Here, using cultured microglia (MG), we found that intracellular formation of BrB in microglia during erythrophagocytosis coincides with the activation of transcription factor AhR, and AhR target genes upregulation, including ligandin, a protein known for retention of BrB solubility, and Mrp1 known for mediating BrB efflux from the cell. Further studies showed that AhR contributed to MG' self-protection from BrB toxicity for a more efficient phagocytosis. Using mouse ICH model, we established that AhR is abundant in MMΦ located near hematoma, and that AhR agonists, ITE, used as treatment for ICH, improved both hematoma clearance and neurological recovery. In support of important role of AhR in microglia in ICH, the selective AhR-deficiency in MG in mice worsened the hematoma clearance and impaired post-ICH recovery and weakened ITE from mediating therapeutic effect.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251371375"},"PeriodicalIF":4.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Franziska Lieschke, Yi Zheng, Josephine Lok, Jan Hendrik Schaefer, Christian Foerch, Klaus van Leyen
{"title":"Dual antiplatelet therapy increases intracerebral hemorrhage and edema after controlled cortical impact and can be partially encountered by 12/15-lipoxygenase inhibition.","authors":"Franziska Lieschke, Yi Zheng, Josephine Lok, Jan Hendrik Schaefer, Christian Foerch, Klaus van Leyen","doi":"10.1177/0271678X251371376","DOIUrl":"10.1177/0271678X251371376","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is increasingly prevalent in older age groups, many of whom receive dual antiplatelet therapy (DAPT). The impact of DAPT on post-traumatic intracranial hemorrhage (ICH) and mortality remains controversial. This study investigates ICH in a mouse TBI model under DAPT and explores the potential protective effects of 12/15-lipoxygenase (LOX) inhibition. Male C57BL6 mice received aspirin and clopidogrel in drinking water for 3 days before TBI induction via controlled cortical impact (CCI). The 12/15-LOX inhibitor BPN-27332 was administered i.p. 1 h after CCI. ICH and edema volumes were quantified 24 h post-injury, functional outcomes were assessed over 7 days, and lesion volumes were analyzed on day 7. DAPT significantly increased ICH (36.56 ± 7.1 vs 6.72 ± 2.12 mm<sup>2</sup>, <i>p</i> = 0.0004) and edema (21.86% ± 2.0% vs 5.94% ± 2.04%, <i>p</i> = 0.0002). BPN-27332 reduced ICH (29.03 ± 4.97 vs 43.99 ± 4.54 mm<sup>2</sup>, <i>p</i> = 0.038) and edema (7.98% ± 4.61% vs 26.11% ± 3.76%, <i>p</i> = 0.0064) in mice under DAPT. No significant functional differences were observed. Lesion volumes tended to be smaller in the BPN-27332 treated mice. DAPT exacerbates ICH risk in experimental TBI, while 12/15-LOX inhibition may help reduce post-traumatic ICH and edema.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251371376"},"PeriodicalIF":4.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Torben D Pearson, Sarah Bricault, Chi-Hyeon Yoo, Hsiao-Ying Wey
{"title":"PET/CT imaging of the late-gestation fetal brain in pregnant rats: A proof-of-concept study.","authors":"Torben D Pearson, Sarah Bricault, Chi-Hyeon Yoo, Hsiao-Ying Wey","doi":"10.1177/0271678X251370861","DOIUrl":"10.1177/0271678X251370861","url":null,"abstract":"<p><p>Preclinical PET studies offer the opportunity to elucidate molecular mechanisms underlying early neurodevelopment with minimal invasiveness. We demonstrated the feasibility of fetal brain PET in four pregnant rats (<i>n</i> = 42 fetuses). [<sup>18</sup>F]FDG uptake in rat fetuses was readily visualized by PET imaging. Additionally, in vivo fetal brain [<sup>18</sup>F]FDG concentration (standardized uptake value (SUV)) was significantly correlated with ex vivo SUV from matched post-mortem brains (<i>R</i><sup>2</sup> = 0.90, <i>p</i> < 0.001). We further investigated the effect of the dopamine receptor antagonist haloperidol on cerebral glucose metabolism (CMR<sub>glu</sub>) and [<sup>11</sup>C]raclopride binding in maternal and fetal brains. Dopamine D2 receptor blockade by haloperidol resulted in significant decreases (<i>p</i> < 0.001, <i>n</i> = 33 vs 9 fetuses) in in vivo CMR<sub>glu</sub> and ex vivo [<sup>18</sup>F]FDG SUV. Consistently, haloperidol pretreatment significantly decreased [<sup>11</sup>C]raclopride SUV ratio (SUVR) by 17% (<i>p</i> < 0.001, <i>n</i> = 6 vs 6 fetuses) in the fetal whole-brain, using the maternal cerebellum as the reference region. In all, our results show that PET/CT imaging of the fetal rat brain can reliably quantify specific molecular targets in vivo, and future translational studies of neurodevelopment are feasible in this model.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251370861"},"PeriodicalIF":4.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marion Giraud, Dae Hee Yun, Leon P Munting, Kwanghun Chung, Brian J Bacskai, Steven M Greenberg, Matthew P Frosch, Alain Goriely, Susanne J van Veluw, Sylvie Lorthois
{"title":"CAA-related enlarged perivascular spaces are associated with abnormal angioarchitecture in human brain tissue: A key role for white matter atrophy?","authors":"Marion Giraud, Dae Hee Yun, Leon P Munting, Kwanghun Chung, Brian J Bacskai, Steven M Greenberg, Matthew P Frosch, Alain Goriely, Susanne J van Veluw, Sylvie Lorthois","doi":"10.1177/0271678X251369256","DOIUrl":"10.1177/0271678X251369256","url":null,"abstract":"<p><p>Cerebral Amyloid Angiopathy, a common age-related small vessel disease leading to hemorrhagic stroke, shares many characteristics with Alzheimer's disease: toxic amyloid deposits, microvascular alterations and enlarged perivascular spaces (EPVS). Together, PVS enlargement, reduced amyloid-β clearance and further accumulation form a vicious cycle underlying disease progression. Yet, the neuropathological correlates of EPVS, including the associated angioarchitecture, are poorly understood. We provide quantitative 3D reconstructions of human brain microvascular networks and their topographical associations with EPVS in large volumes of cleared human tissue spanning over the gray/white matter interface. We reveal the existence of six vessel/PVS morphotypes, including sinusoid and helical vessels, enclosed in increasingly enlarged PVS, and increasingly disconnected from their surrounding network. Based on the buckling of elongated structures, we discuss how they likely result from generic processes of mechanical origin, driven by white matter atrophy, thus advancing our understanding of the pathophysiological overlap between amyloid-related and cerebrovascular disease.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X251369256"},"PeriodicalIF":4.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}