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}
Andreas Hahn, Murray B Reed, Christian Milz, Pia Falb, Matej Murgaš, Rupert Lanzenberger
{"title":"A unified approach for identifying PET-based neuronal activation and molecular connectivity with the functional PET toolbox.","authors":"Andreas Hahn, Murray B Reed, Christian Milz, Pia Falb, Matej Murgaš, Rupert Lanzenberger","doi":"10.1177/0271678X251370831","DOIUrl":"10.1177/0271678X251370831","url":null,"abstract":"<p><p>Functional PET (fPET) identifies stimulation-specific changes of physiological processes, individual molecular connectivity and group-level molecular covariance. Since there is currently no consistent analysis approach available for these techniques, we present a toolbox for unified fPET assessment. The toolbox supports analysis of data obtained with a variety of radiotracers, scanners, experimental protocols, cognitive tasks and species. It includes general linear model (GLM)-based assessment of task-specific effects, percent signal change and absolute quantification, and data-driven independent component analysis (ICA). It allows computation of molecular connectivity via temporal correlations of PET signals and molecular covariance as between-subject covariance using static images. Toolbox performance was evaluated by comparison to previous results obtained using established protocols, demonstrating strong agreement (<i>r</i> = 0.91-0.99). Stimulation-induced changes in metabolism ([<sup>18</sup>F]FDG) and neurotransmitter dynamics (6-[<sup>18</sup>F]FDOPA, [<sup>11</sup>C]AMT) were detected across different cognitive tasks. Molecular connectivity demonstrated metabolic interactions between networks, whereas group-level covariance highlighted interhemispheric relationships. These results underscore the toolbox's flexibility in capturing dynamic molecular processes. The toolbox offers a comprehensive, reproducible, user-friendly approach for analyzing fPET data across various experimental settings. This facilitates sharing of analyses pipelines and comparison across centres to advance the study of brain metabolism and neurotransmitter dynamics in health and 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":"271678X251370831"},"PeriodicalIF":4.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014283","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}
Maider Garbizu, Naroa Mocha-Muñoz, Esther Rubio-López, Laura Palacios, Laura Aguado, María Ardaya, Ana Joya, Unai Alduntzin, Sandra Plaza-García, Daniel Padro, Vanessa Gómez-Vallejo, Unai Cossío, Makoto Higuchi, Pedro Ramos-Cabrer, José Luis Zugaza, Jordi Llop, Abraham Martín
{"title":"Longitudinal imaging evaluation of the inflammatory role of purinergic A<sub>2</sub>A receptors during subacute and chronic ischemic stroke.","authors":"Maider Garbizu, Naroa Mocha-Muñoz, Esther Rubio-López, Laura Palacios, Laura Aguado, María Ardaya, Ana Joya, Unai Alduntzin, Sandra Plaza-García, Daniel Padro, Vanessa Gómez-Vallejo, Unai Cossío, Makoto Higuchi, Pedro Ramos-Cabrer, José Luis Zugaza, Jordi Llop, Abraham Martín","doi":"10.1177/0271678X251370835","DOIUrl":"10.1177/0271678X251370835","url":null,"abstract":"<p><p>Adenosine A<sub>2</sub> receptors (A<sub>2</sub>ARs) have shown promising therapeutic properties despite their controversial role in modulating stroke outcome. However, the temporal evolution of cerebral A<sub>2</sub>ARs density after cerebral ischemia and its subsequent neuroinflammatory response have been scarcely explored. In this study, the expression of A<sub>2</sub>ARs after transient middle cerebral artery occlusion (MCAO) was evaluated in rats by positron emission tomography (PET) with [<sup>11</sup>C]SCH442416 and immunohistochemistry (IHC). In addition, the role of A<sub>2</sub>ARs in stroke inflammation with pharmacological modulation was assessed with magnetic resonance imaging (MRI), PET imaging with [<sup>18</sup>F]DPA-714 (TSPO), IHC, western-blot, and autoradiography. After cerebral ischemia, [<sup>11</sup>C]SCH442416 and IHC revealed neural expression of A<sub>2</sub>ARs in the striatum in healthy brains, followed by a binding decrease at day 1 and a subsequent significant increase at day 3 after ischemia in microglia and infiltrated leukocytes. Furthermore, activation of A<sub>2</sub>ARs with the agonist CGS-21680 resulted in a reduction in stroke volume, along with an increase in TSPO expression in immune cells in the striatum. Our results provide novel evidence on A<sub>2</sub>ARs density dynamics after cerebral ischemia that might guide the therapeutic management of stroke by modulating adenosine receptors.</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":"271678X251370835"},"PeriodicalIF":4.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014276","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}
William W Wroe, Hussein A Zeineddine, Spiros L Blackburn, Jaroslaw Aronowski, Devin W McBride
{"title":"The role of neutrophils in vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: Is it time for a SAH clinical trial targeting neutrophils?","authors":"William W Wroe, Hussein A Zeineddine, Spiros L Blackburn, Jaroslaw Aronowski, Devin W McBride","doi":"10.1177/0271678X251370858","DOIUrl":"10.1177/0271678X251370858","url":null,"abstract":"<p><p>Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological disease, and one of the primary drivers of morbidity after aneurysm rupture is the phenomenon of delayed cerebral ischemia (DCI). Significant knowledge has been gained over the past two decades of the impact of neuroinflammation in DCI; and neutrophils are now believed to play a major role. There is significant human subject data showing the rise of neutrophil related inflammatory markers and neutrophil's association with poor outcome after aSAH, but as of yet no trials involving human subjects have been done specifically targeting neutrophils. There is however a growing body of evidence in animals models that targeting neutrophils, or their byproducts such as neutrophil extracellular traps improves outcomes. This review summarizes the available evidence of neutrophil's impact in both human subjects and animal models of aSAH and should serve as an impetuous to explore clinical trials in human subjects.</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":"271678X251370858"},"PeriodicalIF":4.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014246","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}
Daniel Sconzo, Felipe Ramirez-Velandia, Alejandro Enriquez-Marulanda, Coleman P Riordan, Sandeep Muram, Nima Aghdam, Philipp Taussky, Christopher S Ogilvy
{"title":"Reversible edema after radiosurgery for arteriovenous malformations (AVMs): Inflow and outflow imbalance.","authors":"Daniel Sconzo, Felipe Ramirez-Velandia, Alejandro Enriquez-Marulanda, Coleman P Riordan, Sandeep Muram, Nima Aghdam, Philipp Taussky, Christopher S Ogilvy","doi":"10.1177/0271678X251358986","DOIUrl":"10.1177/0271678X251358986","url":null,"abstract":"<p><p>We examine the remodeling of arterial feeders and draining veins following Stereotactic Radiosurgery (SRS) and explore their relationship with radiation-induced edema using retrospective data from 50 patients with cerebral AVMs treated with CyberKnife between 2010 and 2023 at a single center. Univariate analyses were performed. 46% of patients developed post-SRS edema. Patients with edema had larger AVM volumes (4.5 vs. 2.1 cm³; p < 0.01) and showed greater reduction in the diameter of their main draining vein (33% vs. 13%; p < 0.01) and accessory draining vein (24.5% vs. 6%; p < 0.01). Those without edema had a larger reduction in the diameter of the main feeder artery (15% vs. 8%; p = 0.03). Patients with edema showed higher change in resistance to outflow in the main draining vein (406% vs. 71%; p < 0.01) and second largest vein (192% vs. 27%; p < 0.01), while those without edema showed higher resistance to inflow in the arterial feeder (95% vs. 38%; p = 0.03). There were no differences in radiation dosing (p = 0.97), obliteration rates (p = 0.35), or functional outcomes (p = 0.61) at follow-up. Post-SRS edema in AVMs is associated with higher resistance to outflow seen in a disproportionated greater reduction in the size of draining veins compared to arterial feeders.</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":"271678X251358986"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12401954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144986289","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}
Anina Seidemo, Linda Knutsson, Nirbhay N Yadav, Pia C Sundgren, Ronnie Wirestam, Peter Cm van Zijl
{"title":"Cerebral glucose delivery, transport and metabolism: Theory and modeling using four, three, and two tissue compartments.","authors":"Anina Seidemo, Linda Knutsson, Nirbhay N Yadav, Pia C Sundgren, Ronnie Wirestam, Peter Cm van Zijl","doi":"10.1177/0271678X251366074","DOIUrl":"https://doi.org/10.1177/0271678X251366074","url":null,"abstract":"<p><p>Flux equations describing brain D-glucose uptake are presented for up to four tissue compartments: blood, endothelial intracellular space in the blood-brain barrier (BBB), extravascular-extracellular space (EES), and intracellular space. Transport rates are described by Michaelis-Menten kinetics, including half-saturation constants (<math><msub><mrow><mi>K</mi></mrow><mrow><mi>T</mi></mrow></msub></math>) and maximum rates for transport<math><mi> </mi><msub><mrow><mo>(</mo><mi>T</mi></mrow><mrow><mi>max</mi></mrow></msub><mo>)</mo><mi> </mi></math>over the BBB and the cell membrane (CMB). These transport parameters and the maximum rate for hexokinase-catalyzed metabolism (<math><msubsup><mrow><mi>V</mi></mrow><mrow><mi>max</mi></mrow><mrow><mi>H</mi><mi>K</mi></mrow></msubsup></math>) were determined by numerical fitting of the models to both steady-state and dynamic D-glucose uptake data in human gray matter from MRS. Two-, three-, and four-compartment results are compared, including effects of incorporating an endothelial compartment with unequal ratios (<math><msub><mrow><mi>R</mi></mrow><mrow><mi>A</mi><mo>/</mo><mi>L</mi></mrow></msub></math>) of GLUT1 receptors on abluminal and luminal membranes. Four-compartment fitting with<math><mi> </mi><msub><mrow><mi>R</mi></mrow><mrow><mi>A</mi><mo>/</mo><mi>L</mi></mrow></msub><mo>=</mo><mn>2.0</mn><mi> </mi></math>resulted in<math><mi> </mi><msubsup><mrow><mi>T</mi></mrow><mrow><mi>max</mi></mrow><mrow><mi>BBB</mi></mrow></msubsup><mo>=</mo><mn>0.804</mn><mo>±</mo><mn>0.131</mn><mo> </mo></math>µmol/g/min,<math><mi> </mi><msubsup><mrow><mi>K</mi></mrow><mrow><mi>T</mi></mrow><mrow><mi>BBB</mi></mrow></msubsup><mo>=</mo><mn>6.20</mn><mo>±</mo><mn>1.53</mn><mo> </mo></math>mM,<math><mi> </mi><msubsup><mrow><mi>T</mi></mrow><mrow><mi>max</mi></mrow><mrow><mi>CMB</mi></mrow></msubsup><mo>=</mo><mn>1.04</mn><mo>±</mo><mn>0.25</mn><mo> </mo></math>µmol/g/min,<math><mi> </mi><msubsup><mrow><mi>K</mi></mrow><mrow><mi>T</mi></mrow><mrow><mi>CMB</mi></mrow></msubsup><mo>=</mo><mn>3.10</mn><mo>±</mo><mn>0.70</mn><mo> </mo></math>mM and<math><mi> </mi><msubsup><mrow><mi>V</mi></mrow><mrow><mi>max</mi></mrow><mrow><mi>H</mi><mi>K</mi></mrow></msubsup><mo>=</mo><mn>0.260</mn><mo>±</mo><mn>0.039</mn><mo> </mo></math>µmol/g/min, comparing well with the simpler models. A model with at least three tissue compartments (blood, EES, cell) is essential for quantification and interpretation of dynamic glucose-enhanced (DGE) MRI data in brain tumors, where signal intensities depend on compartmental pH in addition to concentration, and where the signal contribution from the EES is dominant. It should also be relevant to PET and MR(S) studies of pathologies where the BBB is compromised.</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":"271678X251366074"},"PeriodicalIF":4.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144986242","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":"Exercise-induced extracellular vesicles derived from platelet-rich plasma improved recovery after ischemic stroke.","authors":"Yoshifumi Miyauchi, Nobukazu Miyamoto, Toshiki Inaba, Hai-Bin Xu, Chikage Kijima, Kenichiro Hira, Nobutaka Hattori, Yuji Ueno","doi":"10.1177/0271678X251369219","DOIUrl":"https://doi.org/10.1177/0271678X251369219","url":null,"abstract":"<p><p>Stroke remains a major global health burden, with limited treatments for chronic ischemic stroke necessitating novel therapies. This study explored the therapeutic potential of platelet-rich plasma (PRP)-derived extracellular vesicles (EVs) in stroke recovery, particularly in exercise-trained rats. PRP-derived EVs from treadmill-loaded and sedentary rats were designated athletes (aPRP-EVs) and non-athlete (nPRP-EVs), respectively. Both were administered to primary cortical neurons exposed to oxygen-glucose deprivation (OGD) and to adult male Wistar/ST rats subjected to permanent middle cerebral artery occlusion (MCAO). Exercise increased CD63, CD31, and transforming growth factor-β1 (TGF-β1) in PRP-derived EVs. In OGD-exposed neurons, aPRP-EVs enhanced viability, elevated phosphorylated neurofilament heavy chain, and reduced intracellular calcium. Canonical pathway analysis showed upregulated TGF-β/SMAD signaling in EV groups versus vehicle, while 'Ca signaling' was downregulated in aPRP-EVs versus nPRP-EVs. In MCAO rats, EVs improved neurological and motor function and reduced neuronal apoptosis at 28 days, with aPRP-EVs promoting earlier, greater recovery and infarct reduction. These effects correlated with TGF-β1 upregulation, SMAD4 nuclear translocation, reduced NMDAR2B expression, and enhanced axonal growth in the peri-infarct region. PRP-derived EVs, particularly from exercise-trained donors, enhance neuroregeneration and functional recovery in chronic ischemic stroke via TGF-β/SMAD and calcium signaling modulation.</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":"271678X251369219"},"PeriodicalIF":4.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144986245","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}
Ning Ding, Ben Xiang, Huiwen Jiang, Yao Yu, Jian Liu, Yuqian Zhao, Jingmin Luan, Yanqiu Yang, Yi Wang, Zhenhe Ma
{"title":"OCT-PAM dual-mode imaging to evaluate early ischemic stroke in rats.","authors":"Ning Ding, Ben Xiang, Huiwen Jiang, Yao Yu, Jian Liu, Yuqian Zhao, Jingmin Luan, Yanqiu Yang, Yi Wang, Zhenhe Ma","doi":"10.1177/0271678X251369613","DOIUrl":"https://doi.org/10.1177/0271678X251369613","url":null,"abstract":"<p><p>Early diagnosis of ischemic stroke is crucial for timely intervention and saving brain function. The mechanisms of stroke are complex, involving multiple parameters such as blood flow perfusion, tissue status, and oxygenation levels. These parameters interact with each other, necessitating multiple systems to evaluate. The animal model must be moved among systems for various systems monitoring, which complicates the operation and may induce additional interference. Here, we propose a non-contact all-optic OCT-PAM dual-mode imaging system for monitoring rat cortex states. The compact probe enables facilitating long-term multi-parameter observation. Using the system, we quantitatively monitored the state of the rat cortex of ischemic stroke during the acute phase, including blood perfusion density, vessel diameter, vessel length, optical attenuation coefficient, and photoacoustic absorption. We observed reduced perfusion in the affected cortex, contralateral perfusion increases, and vasodilation, suggesting collateral circulation activation. Additionally, increased optical attenuation and photoacoustic absorption in the stroke area were linked to blood-brain barrier changes. This OCT-PAM system and its quantitative analysis method offer a promising tool for early ischemic stroke diagnosis and exploring underlying molecular and cellular mechanisms.</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":"271678X251369613"},"PeriodicalIF":4.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144986228","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}