Crhistian-Mario Oblitas, Ana Sampedro-Viana, Sabela Fernández-Rodicio, Manuel Rodríguez-Yáñez, Iria López-Dequidt, Arturo Gonzalez-Quintela, Antonio J Mosqueira, Jacobo Porto-Álvarez, Javier Martínez Fernández, Marcos Bazarra-Barreiros, María Teresa Abengoza-Bello, Sara Ortega-Espina, Alberto Ouro, Francisco Campos, Tomás Sobrino, José Castillo, Maria Luz Alonso-Alonso, Pablo Hervella, Ramón Iglesias-Rey
{"title":"Hyperthermia and Early Growth of Cerebral Infarct: The Potential Role of Blood-Brain Barrier Permeability.","authors":"Crhistian-Mario Oblitas, Ana Sampedro-Viana, Sabela Fernández-Rodicio, Manuel Rodríguez-Yáñez, Iria López-Dequidt, Arturo Gonzalez-Quintela, Antonio J Mosqueira, Jacobo Porto-Álvarez, Javier Martínez Fernández, Marcos Bazarra-Barreiros, María Teresa Abengoza-Bello, Sara Ortega-Espina, Alberto Ouro, Francisco Campos, Tomás Sobrino, José Castillo, Maria Luz Alonso-Alonso, Pablo Hervella, Ramón Iglesias-Rey","doi":"10.1007/s12975-025-01349-x","DOIUrl":"https://doi.org/10.1007/s12975-025-01349-x","url":null,"abstract":"<p><p>Hyperthermia within the first 24 h following ischemic stroke (IS) has been associated with poor outcomes. We sought to determine whether blood-brain barrier (BBB) permeability contributes to the relationship between hyperthermia and early infarct growth (EIG). A retrospective analysis was conducted on a prospective stroke biobank. EIG was defined as the percentage difference between the initial volume (mL) determined by the diffusion-weighted imaging at admission and the volume (mL) from the control CT image on the 4 th-7 th day. Hyperthermia was defined as an axillary body temperature ≥ 37.5 °C within the first 24 h. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) serum levels were measured by ELISA. One-hundred and two (19.7%) patients showed EIG from a cohort of 519 patients (45.6% females). Linear correlation was observed for axillar body temperature and EIG (Pearson's r = 0.46; p < 0.001). sTWEAK serum levels showed a c-statistic of 0.74 (95% CI: 0.69-0.79), with an optimal cut-off point > 3000 pg/mL for EIG prediction. Moreover, microalbuminuria levels strongly correlated with sTWEAK levels (Pearson's r = 0.75; p < 0.001). In the multivariate analysis for EIG was observed an independent association with hyperthermia (adjusted OR 24.21; 95% CI: 12.03-39.12), sTWEAK levels > 3000 pg/mL (adjusted OR 16.43; 95% CI: 3.71-72.70), leukoaraiosis (adjusted OR 10.42; 95% CI: 2.68-39.08), and microalbuminuria (adjusted OR 1.02; 95% CI: 1.00-1.12). In our cohort, hyperthermia was independently associated with EIG after IS. The fact that microalbuminuria, leukoaraiosis, and sTWEAK were also associated with EIG suggests a relationship with increased BBB permeability.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804321","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}
Mudassir Farooqui, Afshin A Divani, Milagros Galecio-Castillo, Ameer E Hassan, Mouhammad A Jumaa, Marc Ribo, Michael Abraham, Nils Petersen, Johanna Fifi, Waldo R Guerrero, Amer M Malik, James E Siegler, Thanh N Nguyen, Sunil A Sheth, Albert J Yoo, Guillermo Linares, Nazli Janjua, Darko Quispe-Orozco, Asad Ikram, Wondewossen G Tekle, Syed F Zaidi, Cynthia B Zevallos, Federica Rizzo, Tiffany Barkley, Reade De Leacy, Jane Khalife, Mohamad Abdalkader, Sergio Salazar-Marioni, Jazba Soomro, Weston Gordon, Aaron Rodriguez-Calienes, Juan Vivanco-Suarez, Charoskhon Turabova, Maxim Mokin, Dileep R Yavagal, Santiago Ortega-Gutierrez
{"title":"Safety Outcomes of Antiplatelet Therapy During Endovascular Treatment of Tandem Lesions in Acute Ischemic Stroke Patients.","authors":"Mudassir Farooqui, Afshin A Divani, Milagros Galecio-Castillo, Ameer E Hassan, Mouhammad A Jumaa, Marc Ribo, Michael Abraham, Nils Petersen, Johanna Fifi, Waldo R Guerrero, Amer M Malik, James E Siegler, Thanh N Nguyen, Sunil A Sheth, Albert J Yoo, Guillermo Linares, Nazli Janjua, Darko Quispe-Orozco, Asad Ikram, Wondewossen G Tekle, Syed F Zaidi, Cynthia B Zevallos, Federica Rizzo, Tiffany Barkley, Reade De Leacy, Jane Khalife, Mohamad Abdalkader, Sergio Salazar-Marioni, Jazba Soomro, Weston Gordon, Aaron Rodriguez-Calienes, Juan Vivanco-Suarez, Charoskhon Turabova, Maxim Mokin, Dileep R Yavagal, Santiago Ortega-Gutierrez","doi":"10.1007/s12975-023-01214-9","DOIUrl":"10.1007/s12975-023-01214-9","url":null,"abstract":"<p><p>Risk of hemorrhage remains with antiplatelet medications required with carotid stenting during endovascular therapy (EVT) for tandem lesion (TLs). We evaluated the safety of antiplatelet regimens in EVT of TLs. This multicenter study included anterior circulation TL patients from 2015 to 2020, stratified by periprocedural EVT antiplatelet strategy: (1) no antiplatelets, (2) single oral, (3) dual oral, and (4) intravenous IV (in combination with single or dual oral). Primary outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were any hemorrhage, favorable functional status (mRS 0-2) at 90 days, successful reperfusion (mTICI score ≥ 2b), in-stent thrombosis, and mortality at 90 days. Of the total 691 patients, 595 were included in the final analysis. One hundred and nineteen (20%) received no antiplatelets, 134 (22.5%) received single oral, 152 (25.5%) dual oral, and 196 (31.9%) IV combination. No significant association was found for sICH (ref: no antiplatelet: 5.7%; single:4.2%; aOR 0.64, CI 0.20-2.06, p = 0.45, dual:1.9%; aOR 0.35, CI 0.09-1.43, p = 0.15, IV combination: 6.1%; aOR 1.05, CI 0.39-2.85, p = 0.92). No association was found for parenchymal or petechial hemorrhage. Odds of successful reperfusion were significantly higher with dual oral (aOR 5.85, CI 2.12-16.14, p = 0.001) and IV combination (aOR 2.35, CI 1.07-5.18, p = 0.035) compared with no antiplatelets. Odds of excellent reperfusion (mTICI 2c/3) were significantly higher for cangrelor (aOR 4.41; CI 1.2-16.28; p = 0.026). No differences were noted for mRS 0-2 at 90 days, in-stent thrombosis, and mortality rates. Administration of dual oral and IV (in combination with single or dual oral) antiplatelets during EVT was associated with significantly increased odds of successful reperfusion without an increased rate of symptomatic hemorrhage or mortality in patients with anterior circulation TLs.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"328-338"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138452658","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}
Qiao Zhang, Jinlin Chen, Jingjing Lin, Ruichao Liang, Min He, Yanchao Wang, Hong Tan
{"title":"Porous Three-Dimensional Polyurethane Scaffolds Promote Scar-Free Endogenous Regeneration After Acute Brain Hemorrhage.","authors":"Qiao Zhang, Jinlin Chen, Jingjing Lin, Ruichao Liang, Min He, Yanchao Wang, Hong Tan","doi":"10.1007/s12975-023-01212-x","DOIUrl":"10.1007/s12975-023-01212-x","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is the most lethal subtype of stroke and is associated with significant morbidity and mortality. Despite advances in the clinical treatment of ICH, limited progress has been made regarding endogenous brain regeneration after ICH. Failure of brain regeneration is mainly attributed to the inhibitive regenerative microenvironment caused by secondary injury after ICH. In this study, we investigated a three-dimensional biodegradable waterborne polyurethane (BWPU) scaffold as a tool to promote brain regeneration after ICH. After implantation into the cavity following hematoma evacuation, these implanted scaffolds could act as a reservoir; store a series of necrotic debris, cytokines, and chemokines; and attract microglia/macrophages to their pores. Subsequently, these microglia/macrophages were polarized into the M1-like subtype to eliminate these substances. This process disperses M1-like immune cells and prevents the formation of dense glial scar-free structures after ICH. Inflammatory cells in scaffolds include scar-free secreted growth factors and extracellular matrix (ECM) proteins, and further induce a M2-like immune cells enriched regeneration-predominant microenvironment to promote endogenous brain regeneration with functional recovery. In summary, in this work, we have revealed the potential and mechanism of the BWPU scaffold as a tool to promote endogenous brain tissue regeneration after ICH.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"299-314"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138296080","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}
Max I Myers, Kevin J Hines, Andrew Gray, Gabrielle Spagnuolo, Robert Rosenwasser, Lorraine Iacovitti
{"title":"Intracerebral Transplantation of Autologous Mesenchymal Stem Cells Improves Functional Recovery in a Rat Model of Chronic Ischemic Stroke.","authors":"Max I Myers, Kevin J Hines, Andrew Gray, Gabrielle Spagnuolo, Robert Rosenwasser, Lorraine Iacovitti","doi":"10.1007/s12975-023-01208-7","DOIUrl":"10.1007/s12975-023-01208-7","url":null,"abstract":"<p><p>While treatments exist for the acute phase of stroke, there are limited options for patients with chronic infarcts and long-term disability. Allogenic mesenchymal stem cells (alloMSCs) show promise for the treatment of stroke soon after ischemic injury. There is, however, no information on the use of autologous MSCs (autoMSCs), delivered intracerebrally in rats with a chronic infarct. In this study, rats underwent middle cerebral artery occlusion (MCAO) to induce stroke followed by bone marrow aspiration and MSC expansion in a closed bioreactor. Four weeks later, brain MRI was obtained and autoMSCs (1 × 10<sup>6</sup>, 2.5 × 10<sup>6</sup> or 5 × 10<sup>6</sup>; n = 6 each) were stereotactically injected into the peri-infarct and compared to controls (MCAO only; MCAO + PBS; n = 6-9). Behavior was assessed using the modified neurological severity score (mNSS). For comparison, an additional cohort of MCAO rats were implanted with 2.5 × 10<sup>6</sup> alloMSCs generated from a healthy rat. All doses of autoMSCs produced significant improvement (54-70%) in sensorimotor function 60 days later. In contrast, alloMSCs improved only 31.7%, similar to that in PBS controls 30%. Quantum dot-labeled auto/alloMSCs were found exclusively at the implantation site throughout the post-transplantation period with no tumor formation on MRI or Ki67 staining of engrafted MSCs. Small differences in stroke volume and no differences in corpus callosum width were observed after MSC treatment. Stroke-induced glial reactivity in the peri-infarct was long-lasting and unabated by auto/alloMSC transplantation. These studies suggest that intracerebral transplantation of autoMSCs as compared to alloMSCs may be a promising treatment in chronic stroke.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"248-261"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427118","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}
Jacopo Bellomo, Martina Sebök, Vittorio Stumpo, Christiaan H B van Niftrik, Darja Meisterhans, Marco Piccirelli, Lars Michels, Beno Reolon, Giuseppe Esposito, Tilman Schubert, Zsolt Kulcsar, Andreas R Luft, Susanne Wegener, Luca Regli, Jorn Fierstra
{"title":"Blood Oxygenation Level-Dependent Cerebrovascular Reactivity-Derived Steal Phenomenon May Indicate Tissue Reperfusion Failure After Successful Endovascular Thrombectomy.","authors":"Jacopo Bellomo, Martina Sebök, Vittorio Stumpo, Christiaan H B van Niftrik, Darja Meisterhans, Marco Piccirelli, Lars Michels, Beno Reolon, Giuseppe Esposito, Tilman Schubert, Zsolt Kulcsar, Andreas R Luft, Susanne Wegener, Luca Regli, Jorn Fierstra","doi":"10.1007/s12975-023-01203-y","DOIUrl":"10.1007/s12975-023-01203-y","url":null,"abstract":"<p><p>In acute ischemic stroke due to large-vessel occlusion (LVO), the clinical outcome after endovascular thrombectomy (EVT) is influenced by the extent of autoregulatory hemodynamic impairment, which can be derived from blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR). BOLD-CVR imaging identifies brain areas influenced by hemodynamic steal. We sought to investigate the presence of steal phenomenon and its relationship to DWI lesions and clinical deficit in the acute phase of ischemic stroke following successful vessel recanalization.From the prospective longitudinal IMPreST (Interplay of Microcirculation and Plasticity after ischemic Stroke) cohort study, patients with acute ischemic unilateral LVO stroke of the anterior circulation with successful endovascular thrombectomy (EVT; mTICI scale ≥ 2b) and subsequent BOLD-CVR examination were included for this analysis. We analyzed the spatial correlation between brain areas exhibiting BOLD-CVR-associated steal phenomenon and DWI infarct lesion as well as the relationship between steal phenomenon and NIHSS score at hospital discharge.Included patients (n = 21) exhibited steal phenomenon to different extents, whereas there was only a partial spatial overlap with the DWI lesion (median 19%; IQR, 8-59). The volume of steal phenomenon outside the DWI lesion showed a positive correlation with overall DWI lesion volume and was a significant predictor for the NIHSS score at hospital discharge.Patients with acute ischemic unilateral LVO stroke exhibited hemodynamic steal identified by BOLD-CVR after successful EVT. Steal volume was associated with DWI infarct lesion size and with poor clinical outcome at hospital discharge. BOLD-CVR may further aid in better understanding persisting hemodynamic impairment following reperfusion therapy.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"207-216"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50163040","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}
Qiang Hao, Haibin Zhang, Heze Han, Hengwei Jin, Li Ma, Ruinan Li, Zhipeng Li, Anqi Li, Kexin Yuan, Qinghui Zhu, Ke Wang, Runting Li, Fa Lin, Chengzhuo Wang, Yukun Zhang, Hongwei Zhang, Yang Zhao, Weitao Jin, Dezhi Gao, Geng Guo, Debin Yan, Jun Pu, Shuai Kang, Xun Ye, Youxiang Li, Shibin Sun, Hao Wang, Yu Chen, Xiaolin Chen, Yuanli Zhao
{"title":"Recurrence of Cerebral Arteriovenous Malformation Following Complete Obliteration Through Endovascular Embolization.","authors":"Qiang Hao, Haibin Zhang, Heze Han, Hengwei Jin, Li Ma, Ruinan Li, Zhipeng Li, Anqi Li, Kexin Yuan, Qinghui Zhu, Ke Wang, Runting Li, Fa Lin, Chengzhuo Wang, Yukun Zhang, Hongwei Zhang, Yang Zhao, Weitao Jin, Dezhi Gao, Geng Guo, Debin Yan, Jun Pu, Shuai Kang, Xun Ye, Youxiang Li, Shibin Sun, Hao Wang, Yu Chen, Xiaolin Chen, Yuanli Zhao","doi":"10.1007/s12975-023-01215-8","DOIUrl":"10.1007/s12975-023-01215-8","url":null,"abstract":"<p><p>Arteriovenous malformation (AVM) recurrence after embolization was rarely reported. This study aimed to explore the potential risk factors of recurrence in angiographically obliterated AVMs treated with endovascular embolization. This study reviewed AVMs treated with embolization only in a prospective multicenter registry from August 2011 to December 2021, and ultimately included 92 AVMs who had achieved angiographic obliteration. Recurrence was assessed by follow-up digital subtraction angiography (DSA) or magnetic resonance imaging (MRI). Hazard ratios (HRs) with 95% confidence intervals were calculated using Cox proportional hazards regression models. Nineteen AVMs exhibited recurrence on follow-up imaging. The recurrence rates after complete obliteration at 6 months, 1 year, and 2 years were 4.35%, 9.78%, and 13.0%, respectively. Multivariate Cox regression analysis identified diffuse nidus (HR 3.208, 95% CI 1.030-9.997, p=0.044) as an independent risk factor for recurrence. Kaplan-Meier analysis confirmed a higher cumulative risk of recurrence with diffuse nidus (log-rank, p=0.016). Further, in the exploratory analysis of the effect of embolization timing after AVM rupture on recurrence after the complete obliteration, embolization within 7 days of the hemorrhage was found as an independent risk factor (HR 4.797, 95% CI 1.379-16.689, p=0.014). Kaplan-Meier analysis confirmed that embolization within 7 days of the hemorrhage was associated with a higher cumulative risk of recurrence in ruptured AVMs (log-rank, p<0.0001). This study highlights the significance of diffuse nidus as an independent risk factor for recurrence after complete embolization of AVMs. In addition, we identified a potential recurrent risk associated with early embolization in ruptured AVMs.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"339-349"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92156840","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":"Neural Stem Cell Extracellular Vesicles Carrying YBX1 Inhibited Neuronal Pyroptosis Through Increasing m6A-modified GPR30 Stability and Expression in Ischemic Stroke.","authors":"Jun Peng, Jun He, Long Lin, You Li, Ying Xia","doi":"10.1007/s12975-023-01210-z","DOIUrl":"10.1007/s12975-023-01210-z","url":null,"abstract":"<p><p>Neural stem cell-derived extracellular vesicles (NSC-derived EVs) alleviated ischemic stroke (IS) by suppressing the activation of nucleotide-binding domain leucine-rich repeats family protein 3 (NLRP3) inflammasome and neuronal pyroptosis. However, the specific mechanism needs further investigation. qRT-qPCR, Western blotting, and immunofluorescence detected related gene expression. Immunofluorescent analyzed the expression of Ki-67, βIII-Tubulin (Tuj1), and GFAP. Lactate dehydrogenase (LDH) release and IL-1β and IL-18 levels were analyzed by LDH and ELISA kits. TTC staining evaluated the infarction of brain tissues. Flow cytometric analysis measured caspase-1 activity. M6A methylated RNA immunoprecipitation PCR (MeRIP-PCR) measured methylation levels of G protein-coupled receptor 30 (GPR30). RIP and Co-IP analyzed the interactions of Y box binding protein (YBX1)/GPR30, YBX1/IGF2BP1 and NLRP3/speckle-type POZ protein (SPOP), as well as the ubiquitination levels of NLRP3. NSC-derived EVs inhibited the ischemia-reperfusion (I/R) injury of rats and the neuronal pyroptosis induced by oxygen-glucose deprivation/reoxygenation (OGD/R). Knockdown of EVs carrying YBX1 or GPR30 silencing abolished these inhibiting effects. GPR30 mRNA and IGF2BP1 protein were enriched by YBX1 antibody. YBX1 enhanced the stability of m6A-modified GPR30 by interacting with IGF2BP1 and thus promoting GPR30 expression. Knockdown of IGF2BP1 suppressed the binding between YBX1 and GPR30 mRNA. GPR30 promoted NLRP3 ubiquitination by interacting with SPOP. EVs carrying YBX1 could reduce the infarction of brain tissues and inhibit neuronal pyroptosis in rats with I/R injury. NSC-derived EVs carrying YBX1 increased the stability of m6A-modified GPR30 by interacting with IGF2BP1; the upregulation of GPR30 inhibited the activation of NLRP3 inflammasome through promoting NLRP3 ubiquitination by SPOP, ultimately suppressing the neuronal pyroptosis in IS.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"262-279"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107592275","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}
Bharath Chelluboina, Soomin Jeong, Charles Kozhikkadan Davis, Suresh L Mehta, Raghu Vemuganti
{"title":"Therapeutic Potential of Intravenous miR-21 Mimic after Stroke Following STAIR Criteria.","authors":"Bharath Chelluboina, Soomin Jeong, Charles Kozhikkadan Davis, Suresh L Mehta, Raghu Vemuganti","doi":"10.1007/s12975-023-01223-8","DOIUrl":"10.1007/s12975-023-01223-8","url":null,"abstract":"<p><p>The microRNA-21 (miR-21) levels in the brain are crucial in determining post-stroke brain damage and recovery. The miR-21 exerts neuroprotection by targeting mRNAs that translate proteins that mediate brain damage. We currently determined the efficacy and efficiency of intravenously administered miR-21 mimic after focal cerebral ischemia in mice. Adult male mice were intravenously administered with either control mimic or miR-21 mimic at 5 min/2 h after reperfusion following 1 h transient middle cerebral artery occlusion to determine the therapeutic window of miR-21 mimic. Adult female, type-2 diabetic male, aged male, and aged female mice were administered with control/miR-21 mimic at 5 min after reperfusion following 35 min/1 h transient middle cerebral artery occlusion. Early administration of miR-21 mimic significantly reduced brain damage and promoted long-term recovery after stroke. Further, miR-21 mimic is more effective in males than in females subjected to stroke. However, delayed treatment with miR-21 mimic is not efficacious, and type-2 diabetic subjects show no improvement with miR-21 mimic treatment.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"403-409"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138831707","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}
Reinier W P Tack, Claudia Amboni, Danny van Nuijs, Marcela Pekna, Mervyn D I Vergouwen, Gabriel J E Rinkel, Elly M Hol
{"title":"Inflammation, Anti-inflammatory Interventions, and Post-stroke Cognitive Impairment: a Systematic Review and Meta-analysis of Human and Animal Studies.","authors":"Reinier W P Tack, Claudia Amboni, Danny van Nuijs, Marcela Pekna, Mervyn D I Vergouwen, Gabriel J E Rinkel, Elly M Hol","doi":"10.1007/s12975-023-01218-5","DOIUrl":"10.1007/s12975-023-01218-5","url":null,"abstract":"<p><p>The pathophysiology and treatment of post-stroke cognitive impairment (PSCI) are not clear. Stroke triggers an inflammatory response, which might affect synapse function and cognitive status. We performed a systematic review and meta-analysis to assess whether patients with PSCI have increased levels of inflammatory markers and whether anti-inflammatory interventions in animals decrease PSCI. We systematically searched PubMed, EMBASE, and PsychInfo for studies on stroke. For human studies, we determined the standardized mean difference (SMD) on the association between PSCI and markers of inflammation. For animal studies, we determined the SMD of post-stroke cognitive outcome after an anti-inflammatory intervention. Interventions were grouped based on proposed mechanism of action. In patients, the SMD of inflammatory markers for those with versus those without PSCI was 0.46 (95% CI 0.18; 0.76; I<sup>2</sup> = 92%), and the correlation coefficient between level of inflammation and cognitive scores was - 0.25 (95% CI - 0.34; - 0.16; I<sup>2</sup> = 75%). In animals, the SMD of cognition for those treated with versus those without anti-inflammatory interventions was 1.43 (95% CI 1.12; 1.74; I<sup>2</sup> = 83%). The largest effect sizes in treated animals were for complement inhibition (SMD = 1.94 (95% CI 1.50; 2.37), I<sup>2</sup> = 51%) and fingolimod (SMD = 2.1 (95% CI 0.75; 3.47), I<sup>2</sup> = 81%). Inflammation is increased in stroke survivors with cognitive impairment and is negatively correlated with cognitive functioning. Anti-inflammatory interventions seem to improve cognitive functioning in animals. Complement inhibition and fingolimod are promising therapies on reducing PSCI.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"535-546"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138446297","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}
Sarina Falcione, Elena Spronk, Danielle Munsterman, Twinkle Joy, Roobina Boghozian, Glen C Jickling
{"title":"Sex Differences in Thrombin Generation in Patients with Acute Ischemic Stroke.","authors":"Sarina Falcione, Elena Spronk, Danielle Munsterman, Twinkle Joy, Roobina Boghozian, Glen C Jickling","doi":"10.1007/s12975-023-01200-1","DOIUrl":"10.1007/s12975-023-01200-1","url":null,"abstract":"<p><p>Sex differences in stroke exist, including variation in stroke risk and outcome. Differences in thrombin generation may contribute to this variation between females and males. To examine this, we assessed sex differences in thrombin generation between females and males with acute ischemic stroke and the relationship to blood cell gene expression. In 97 patients with acute ischemic stroke, thrombin generation was measured by thrombin generation assay. Blood cell gene expression was measured by microarray. Differences in thrombin generation between sexes were identified and the relationship to blood cell gene expression examined. Genes associated with sex differences in thrombin generation were analyzed by functional pathway analysis. Females and males had similar overall capacity to generate thrombin. The peak thrombin generated in females was 468.8 nM (SD 91.6), comparable to males (479.3nM;SD 90.8; p = 0.58). Lag time, time to peak thrombin, and endogenous thrombin potential were also similar between females and males. While overall thrombin generation was comparable between females and males with stroke, differences in genes that promote this thrombin generation exist. Females with high peak thrombin had an increase in genes that promote thrombosis, and platelet activation. In contrast, males with high peak thrombin had a decrease in genes involved in thrombus degradation. Females and males with acute ischemic stroke have similar capacity to generate thrombin, however, differences may exist in how this thrombin generation is achieved, with females having increased thrombin signaling, and platelet activation, and males having decreased thrombus degradation. This suggests regulatory differences in thrombosis may exist between females and males that may contribute to sex differences in stroke.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"169-177"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138177366","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}