Translational Stroke Research最新文献

{"title":"CircRNA circ_0004058 Modulates Early Brain Injury in Subarachnoid Hemorrhage Through miR-221-3p and VE1 Activation Pathway.","authors":"Hua Gu, Yong Cai","doi":"10.1007/s12975-025-01383-9","DOIUrl":"https://doi.org/10.1007/s12975-025-01383-9","url":null,"abstract":"<p><p>Subarachnoid hemorrhage (SAH) frequently results in early brain injury (EBI), which remains a major barrier to favorable neurological recovery. Understanding the molecular underpinnings of EBI is crucial for developing targeted therapeutics. Circular RNAs (circRNAs) have emerged as influential molecular players in various brain injury contexts. This study focuses on one such molecule, circ_0004058, examining its impact on EBI through interaction with miR-221-3p and the VE1 signaling pathway. Utilizing an established SAH rodent model, our team conducted a detailed investigation of the expression patterns and interactions involving circ_0004058. Our analyses revealed a significant post-SAH upregulation of circ_0004058, which affected miR-221-3p activity and VE1 signaling. Furthermore, functional modulation of circ_0004058 expression altered the severity of EBI, presenting evidence that it serves as a critical determinant in the injury process. The results suggest that circ_0004058 holds promise as a therapeutic target, offering new possibilities for the development of strategies to mitigate SAH-induced brain damage. Through this study, circ_0004058 is highlighted not only as a biomarker but also as a possible avenue for therapeutic modulation in SAH management.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Effects of Murine Stroke Models on Dopaminergic Neurons, Glial Responses, and Neurobehavioral Outcomes.","authors":"Sidra Tabassum, Heng Hu, Silin Wu, Shuning Huang, Bosco Seong Kyu Yang, Chang-Hun Lee, Aaron W Gusdon, Xuefang S Ren","doi":"10.1007/s12975-025-01381-x","DOIUrl":"10.1007/s12975-025-01381-x","url":null,"abstract":"<p><p>Stroke is a leading cause of disability worldwide, often resulting in persistent motor, cognitive, and emotional impairments. While the hippocampus and amygdala play critical roles in post-stroke behavioral changes, specific neuronal alterations and prolonged glial responses within these regions across different stroke types remain unclear. This study investigates the behavioral, neuronal, and glial effects of subarachnoid hemorrhage (SAH), transient middle cerebral artery occlusion (tMCAO), and photothrombotic stimulation (PTS) in mice. SAH and tMCAO models exhibited significant motor deficits, spatial and recognition memory impairments, and increased anxiety- and depressive-like behaviors, whereas the PTS model showed similar motor and cognitive impairments but lacked affective (anxiety- and depressive-like) behavioral changes. Immunohistochemical analysis revealed increased overlap of tyrosine hydroxylase (TH, a dopaminergic marker) process with NeuN (a neuronal marker) in the dentate gyrus (DG) of SAH and tMCAO mice, highlighting region-specific vulnerability to ischemic damage in the hippocampus. In the amygdala, elevated overlap of TH⁺ process with NeuN in SAH and tMCAO mice suggests enhanced dopaminergic involvement in emotional dysregulation. In contrast, the PTS model did not exhibit any changes in overlap of TH⁺ process with NeuN in either the hippocampus or amygdala, consistent with the absence of affective behavioral deficits. Additionally, SAH and tMCAO models exhibited persistent astrocytic and microglial activation in the amygdala, characterized by increased intensity and density without significant morphological changes, indicative of a chronic inflammatory response. The PTS model also showed increased microglial intensity and density without overt morphological changes, suggesting a more moderate, possibly subclinical inflammatory response. These findings highlight the differential effects of stroke models on behavior, neuronal populations, and glial responses in limbic regions. The pronounced dopaminergic and glial alterations in SAH and tMCAO may underlie post-stroke emotional and cognitive disturbances.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cisternal Contrast-Enhanced MRI Reveals Post-Stroke Glymphatic Impairment and Compensatory Metabolic Waste Clearance via Microglia/Macrophages.","authors":"Chengfeng Sun, Chanchan Li, Luyi Lin, Lekang Yin, Jiaojiao Li, Yan Ren, Weijun Tang, Yanmei Yang","doi":"10.1007/s12975-025-01373-x","DOIUrl":"https://doi.org/10.1007/s12975-025-01373-x","url":null,"abstract":"<p><p>Recent studies have shown that the glymphatic system plays a crucial role in driving hyperacute edema after ischemic stroke. This has sparked interest in understanding how this system changes in later phases of ischemic stroke. In this study, we utilized cisternal contrast-enhanced magnetic resonance imaging (CE-MRI) and immunofluorescence staining to investigate glymphatic system alterations at subacute and chronic phases of ischemic stroke. Middle cerebral artery occlusion (MCAO) for 90 min in Sprague-Dawley rats was used to mimic ischemic stroke. A total of 20 rats were randomly divided into four groups: sham group, MCAO 1-week group, MCAO 2-week group, and MCAO 2-month group. Our results showed the glymphatic system was spatially and temporally heterogeneously impaired in the peri-infarct area at subacute phase, even lasting for chronic phase. Specially, we found retention of contrast after cisternal CE-MRI in the infarct core and peri-infarct area at subacute phase of ischemic stroke, which corresponded to the distribution of microglia/macrophages. Our results indicated that ischemic stroke contributed to long-term glymphatic impairment and waste retention, and cisternal CE-MRI delayed enhancement could reflect the retention of waste and activation of microglia/macrophages in this process. These findings suggest cisternal CE-MRI might be a useful tool for investigating the interaction between the glymphatic system and microglia/macrophages in waste clearance and neuroinflammation after brain insult.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Remote Ischemic Conditioning in Patients Treated with Endovascular Therapy: A RESIST Trial Post Hoc Study.","authors":"Rolf Ankerlund Blauenfeldt, David Charles Hess, David Gaist, Boris Modrau, Jan Brink Valentin, Søren Paaske Johnsen, Niels Hjort, Anne Brink Behrndtz, Martin Faurholdt Gude, Wenbo Zhao, Jonas Jensen, Grethe Andersen, Claus Ziegler Simonsen","doi":"10.1007/s12975-025-01379-5","DOIUrl":"https://doi.org/10.1007/s12975-025-01379-5","url":null,"abstract":"<p><p>Remote ischemic conditioning (RIC) is a simple, non-invasive procedure that has been shown to be safe and feasible in multiple smaller clinical trials. Recent large randomized controlled trials have yielded mixed results regarding clinical effect. Patients with severe stroke may experience greater benefit from cerebroprotective interventions, highlighting the need for adjunctive therapies to enhance endovascular therapy (EVT) outcomes. This post hoc analysis of the RESIST trial evaluates the effect of RIC in the subgroup of patients who underwent EVT. Eligible patients were adults (≥ 18 years old), independent in activities of daily living, who had prehospital stroke symptoms with a duration of less than 4 h. They were randomized to RIC or sham. The primary analysis was performed using the entire range (\"shift analysis\") of the modified Rankin scale (mRS) at 90 days. A total of 737 patients had acute ischemic stroke, and 134 received EVT. The median (IQR) age was 74 (62, 82) years, median NIHSS was 16 (8, 20), and 52 (39%) were female. Median (IQR) overall adherence to RIC/sham was 81% (56, 96). Intravenous thrombolysis (IVT) was initiated in 76 out of the 134 (57%) EVT-treated patients. There was no significant effect of RIC on mRS in EVT-treated patients, OR (95% CI) 1.26 (0.68-2.32). When IVT was given in addition to EVT, RIC was associated with improved functional outcome at 90 days, adjusted OR 2.46 (1.05, 5.78), p = 0.038 but not without adjunctive IVT, aOR 0.57 (0.21-1.53). The effect of RIC was present only in patients achieving complete reperfusion (mTICI 3) following EVT and IVT (54 out of 134 patients). RIC treatment in addition to IVT and EVT was associated with significantly improved functional outcome at 90 days, observed only in patients who achieved complete reperfusion. These results should only serve as hypothesis-generating for future trials. ClinicalTrials.gov:NCT03481777.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Do Patient Outcomes in Mechanical Thrombectomy for Large-Core Stroke Vary Based on Neuroimaging Modalities Used for Patient Selection? A Multicenter Multinational Study.","authors":"Omar Alwakaa, Rahim Abo Kasem, Felipe Ramirez-Velandia, Aryan Wadhwa, Kimberly Han, Michael R Levitt, Ali Alaraj, Pascal Jabbour, Joon-Tae Kim, Brian Howard, Ali Alawieh, Stacey Quintero Wolfe, Robert M Starke, Marios-Nikos Psychogios, Amir Shaban, Nitin Goyal, Justin Dye, Mohamad Ezzeldin, Shinichi Yoshimura, Daniel Sconzo, Jean Filo, Samuel Pettersson, David Fiorella, Omar Tanweer, Daniele G Romano, Pedro Navia, Hugo Cuellar, Isabel Fragata, Adam Polifka, Justin Mascitelli, Joshua Osbun, Fazeel Siddiqui, Mark Moss, Kaustubh Limaye, Maxim Mokin, Charles Matouk, Min S Park, Waleed Brinjikji, Ergun Daglioglu, Richard Williamson, David J Altschul, Ilko Maier, Roberto Crosa, Benjamin Gory, Ramesh Grandhi, Alexandra Paul, Peter Kan, Walter Casagrande, Shakeel Chowdhry, Michael F Stiefel, Ansaar Rai, Alejandro M Spiotta, Philipp Taussky, Christopher S Ogilvy, Justin H Granstein","doi":"10.1007/s12975-025-01378-6","DOIUrl":"10.1007/s12975-025-01378-6","url":null,"abstract":"<p><p>The role of different imaging modalities-non-contrast CT (NCCT), CT perfusion (CTP), and diffusion-weighted imaging (DWI)-in selecting patients with large-core stroke for endovascular thrombectomy (EVT) is a subject of ongoing debate. This study aims to determine whether patients with large-core acute ischemic stroke (AIS) undergoing EVT triaged with CTP or DWI in addition to NCCT had different clinical outcomes compared to those only triaged with NCCT. We queried the Stroke Thrombectomy and Aneurysm Registry (STAR) for patients enrolled between 2014 and 2023 who presented with anterior-circulation AIS and large ischemic core (ASPECTS < 6) who underwent EVT in 41 stroke centers in the USA, Europe, Asia, and South America. Patients were stratified by the imaging used before EVT. Propensity score matching (PSM) was used to compare balanced cohorts of patients with NCCT vs CTP and NCCT vs DWI. The primary outcome was a favorable 90-day functional status (mRS 0-3). Secondary outcomes included intracerebral hemorrhage (ICH) rates, symptomatic ICH (sICH), and successful/complete recanalization, as determined by mTICI score. A total of 403 patients were included, 121 were selected with NCCT alone, 227 with CTP, and 55 with DWI. Before PSM, 90-day mRS 0-3, successful reperfusion mTICI ≥ 2B, and sICH rates were similar across the three imaging modalities. mTICI-2C or greater rates were highest in DWI (50.9%; p < 0.01), followed by NCCT (41.3%) and CTP (27.8%). Patients selected with CTP had the highest ICH incidence (44.1%; p < 0.01). After 1:1 PSM, 104 pairs of NCCT vs CTP and 36 pairs of NCCT vs DWI were compared. There were no significant differences in any procedural or functional outcome measure between the matched groups, including mTICI ≥ 2C recanalization, 90-day mRS 0-3, ICH rates, and sICH rates. In patients with anterior large-vessel occlusion AIS with low ASPECTS, we found that selecting patients for EVT based on NCCT or employing advanced imaging to elucidate collaterals, infarct volume, and ischemic penumbra does not alter procedural or patient outcomes. NCCT alone may be sufficient to select patients for EVT in this patient population, especially in settings with limited resources.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Profiles of Neuroglial Injury Biomarkers after Ischemic Stroke.","authors":"Karl Sjölin, Björn Röyter, Bianka Forgo, Julia Aulin, Kim Kultima, Johan Lindbäck, Jakob O Ström, Joachim Burman","doi":"10.1007/s12975-025-01380-y","DOIUrl":"10.1007/s12975-025-01380-y","url":null,"abstract":"<p><strong>Objective: </strong>To determine the temporal profiles of glial fibrillary acidic protein (GFAP), neurofilament light (NFL), total tau (t-tau), and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) in plasma the first week after acute ischemic stroke, and identify the optimal time points for assessing infarct volume by these biomarkers.</p><p><strong>Patients & methods: </strong>In this cohort study, biomarker plasma concentrations were determined daily over the first week and at 90 days after symptom onset in patients with acute ischemic stroke. A brain MRI was performed on day three. Temporal variations in biomarker levels were analyzed using linear mixed-effects models, and optimal time points for infarct volume correlation were identified with continuous Pearson analysis.</p><p><strong>Results: </strong>38 patients with a median age of 78 (IQR 72-86) and mean infarct volume of 5.5 (IQR 1.6-17) cm³ were included. We identified three distinct temporal patterns: (1) a parabolic trajectory of GFAP, reaching zenith after three days, (2) a consistent increase in NFL throughout the week, and (3) an initial surge in t-tau and UCHL1 levels, stabilizing by day three. The optimal time point for infarct volume correlation occurred at 119 h for GFAP (r = 0.94, 95% CI: [0.84-0.98]), 144 h for NFL (r = 0.78, [0.47, 0.92]), 122 h for t-tau (r = 0.82, [0.56, 0.93]) and 113 h for UCHL1 (r = 0.83, [0.60, 0.93]).</p><p><strong>Interpretation: </strong>This high-resolution serial sampling of plasma GFAP, NFL, t-tau, and UCHL1 the first week after acute ischemic stroke identified three distinct temporal profiles. These biomarkers provided the most accurate infarct volume assessment 4-6 days after symptom onset.</p><p><strong>Clinicaltrials: </strong>gov NCT03812666 (registration date 2019-01-23).</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter Regarding Article, \"Exploring the Efficacy and Safety of Argatroban as an Adjunct to Antiplatelet Therapy in Ischemic Stroke Patients: a Systematic Review and Meta-Analysis\".","authors":"Yunhe Luo","doi":"10.1007/s12975-025-01382-w","DOIUrl":"https://doi.org/10.1007/s12975-025-01382-w","url":null,"abstract":"","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Ischemic Stroke Patients Based on Plasma Concentrations of Extracellular Vesicles.","authors":"Naomi C Buntsma, Chi M Hau, Mandy Los, Vivien M Chen, Ton G van Leeuwen, Yvo B W E M Roos, Rienk Nieuwland, Aleksandra Gasecka, Edwin van der Pol","doi":"10.1007/s12975-025-01371-z","DOIUrl":"https://doi.org/10.1007/s12975-025-01371-z","url":null,"abstract":"<p><p>Patients presenting with stroke symptoms suffer from either ischemic stroke, hemorrhagic stroke, transient ischemic attacks (TIA), or \"stroke mimics,\" which include benign headaches, epilepsy, and vestibular disorders. As ischemic and hemorrhagic stroke patients require different medical treatments, early identification of the underlying cause of symptoms is essential for tailored and urgent medical intervention. This study investigates whether extracellular vesicles (EVs), present in peripheral blood of patients presenting with stroke symptoms, can be used to identify patients with ischemic stroke. Blood was collected from 155 patients presenting with stroke symptoms in the emergency room and analyzed for EVs by flow cytometry (ethics approval number NL72929.018.20). The primary endpoint was to compare platelet EV concentrations between patients with (n = 66) and without (n = 89) ischemic stroke. Concentrations of EVs from both activated platelets and leukocytes were lower in patients presenting with ischemic stroke compared to other patients (p = 0.038 and p = 0.015, respectively). No significant differences in other EV types were observed. In addition, ischemic stroke patients were older and had a higher diastolic blood pressure compared to patients with other diagnoses. In a multivariable analysis, leukocyte EVs and diastolic blood pressure were independent indicators of ischemic stroke. To conclude, this study demonstrates that the plasma concentration of leukocyte EVs can be useful to identify ischemic stroke patients in an emergency setting.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocyte-derived Exosomal GJA1-20 k Targets Pink1-mediated Mitophagy to Attenuate Traumatic Brain Injury.","authors":"Yalun Li, Wei Chen, Jiugeng Feng","doi":"10.1007/s12975-025-01374-w","DOIUrl":"https://doi.org/10.1007/s12975-025-01374-w","url":null,"abstract":"<p><p>Connexin 43 (Cx43), particularly its truncated isoform GJA1-20 k, has shown promise in mitigating neuronal injury through mitochondrial regulation. This study aimed to investigate the therapeutic potential of astrocyte-derived extracellular vesicles (EVs) enriched with GJA1-20 k (Exo-GJA1-20 k) for treating traumatic brain injury (TBI). Primary astrocytes were isolated and transfected with an adeno-associated viral vector to overexpress GJA1-20 k. EVs were extracted and characterized using nanoparticle tracking analysis and Western blotting. A controlled cortical impact (CCI) model of TBI was established in mice, followed by daily administration of Exo-GJA1-20 k via tail vein injections. Mitochondrial function, neuroinflammation, pyroptosis, and cognitive outcomes were evaluated through molecular assays, histological staining, and behavioral tests, including the Morris Water Maze and open field tests. Exo-GJA1-20 k treatment significantly improved mitochondrial quality control by enhancing mitophagy and reducing mitochondrial dysfunction. Pyroptosis, driven by the NLRP3 inflammasome, was notably suppressed, with significant reductions in NLRP3, ASC, and IL-1β expression levels. Behavioral analyses revealed enhanced cognitive performance, as evidenced by shorter escape latencies in the Morris Water Maze and reduced anxiety-like behaviors in the open field test in Exo-GJA1-20 k-treated mice compared to controls. Importantly, the therapeutic effects of Exo-GJA1-20 k were diminished in Pink1-knockout mice, underscoring the dependence on Pink1-mediated mitophagy. This study demonstrates that Exo-GJA1-20 k exerts neuroprotective effects by modulating the mitophagy-NLRP3 inflammasome axis, alleviating neuroinflammation, and mitigating cognitive deficits in a TBI model. These findings propose a novel therapeutic strategy for addressing TBI-induced neuronal damage and underscore the potential of EV-based therapies for treating neurological disorders.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Association Between Early PaCO₂ Correction Speed and Cerebrovascular Autoregulation in a Porcine Model of Extracorporeal Resuscitation.","authors":"Mingfeng Cao, Camila S Contreras-Rojas, Qihong Wang, Yaman B Ahmed, Jessica Briscoe, Carlos A Pardo, Hannah Rando, Jin Kook Kang, Glenn Whitman, Steve Keller, Tito Porras, Sung-Min Cho","doi":"10.1007/s12975-025-01376-8","DOIUrl":"https://doi.org/10.1007/s12975-025-01376-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Prior clinical research demonstrated that rapid reduction in arterial carbon dioxide (PaCO&lt;sub&gt;2&lt;/sub&gt;) levels during extracorporeal membrane oxygenation (ECMO) is associated with acute brain injury (ABI), which may be due to sudden cerebral vasoconstriction and impaired cerebrovascular autoregulation (CVAR). However, the causal relationship between rapid PaCO&lt;sub&gt;2&lt;/sub&gt; correction and its impact on ABI has not been firmly established due to the lack of high-quality evidence. We aimed to investigate whether rapid PaCO&lt;sub&gt;2&lt;/sub&gt; correction following extracorporeal cardiopulmonary resuscitation (ECPR) causes CVAR impairment and neuronal injury in a porcine model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this prospective preclinical experimental study, six female pigs (mean weight: 50.75 ± 1.89 kg) were subjected to 15 min of ventricular fibrillation and were then supported by ECMO. The return of spontaneous circulation (ROSC) was attempted in animals at 20 min post-ECMO initiation. Arterial blood gas (ABG) was sampled at specific time points, while arterial blood pressure (ABP) and intracranial pressure (ICP) were continuously monitored. Sweep gas flow was set relative to each animal's ECMO flow rate: 100% in the control group, 200% in the rapid correction group, and 25% in the slow correction group. PRx was computed as the Pearson correlation coefficient between 10-s average mean arterial pressure (MAP) and ICP values using 1-min windows updated every 30 s. Experimental phases were defined for data analysis, including baseline, fibrillation, ECMO I (0-10 min after ECMO initiation), ECMO II (10-20 min), and POST-R (post-ROSC, 20-30 min). Linear mixed-effects models were used to assess group-wise differences in ΔPRx over time. Histopathological analysis was performed to quantify neuronal injury across cortical and subcortical regions. Brain tissues were harvested and histologically analyzed for neuronal injury ischemia vulnerable regions: the midbrain, cerebellum, striatum in the basal ganglia, temporal cortex, hypothalamus, and hippocampus.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In the rapid group, PaCO&lt;sub&gt;2&lt;/sub&gt; correction caused a steep drop in PaCO₂-from 60 to approximately 30 mmHg within 5 min-and was associated with impaired CVAR. Following ECMO initiation, the rapid group exhibited a significant rise in ΔPRx, indicating impaired CVAR. Group differences in ΔPRx were significant at ECMO I (F = 8.12, p = 0.001), ECMO II (F = 6.21, p = 0.003), and POST-R (F = 13.47, p &lt; 0.001). At ECMO II, median PRx in the rapid group was 0.50 (IQR: 0.10, 0.78), significantly higher than the control (0.11, IQR: - 0.27, 0.42) and slow (0.38, IQR: - 0.06, 0.55). Histologically, the rapid correction group exhibited significantly increased ischemic neuronal injury in ischemia-prone regions: caudate (43.1% injured neurons vs. 10.6% in control, p = 0.041), putamen (66.6% vs. 23.9%, p = 0.003), temporal cortex (34.9% vs. 8.9%, p = 0.013), and hi","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}