Haoran Qiu, Kai Chen, Yunruo Chen, Yang Yu, Xinlong Ma, Zhaoyang Yuan, Maogui Li, Jianfeng Zhuang, Mingxiang Zhang, Wandong Su, Yunyan Wang, Donghai Wang, Weiying Zhong
{"title":"Integration of Multi-Omics and Machine Learning Identifies TGFB1 and SERPINE1 as Biomarkers of Vascular Smooth Muscle Cell Senescence in Intracranial Aneurysms.","authors":"Haoran Qiu, Kai Chen, Yunruo Chen, Yang Yu, Xinlong Ma, Zhaoyang Yuan, Maogui Li, Jianfeng Zhuang, Mingxiang Zhang, Wandong Su, Yunyan Wang, Donghai Wang, Weiying Zhong","doi":"10.1007/s12975-026-01419-8","DOIUrl":"10.1007/s12975-026-01419-8","url":null,"abstract":"<p><p>Intracranial aneurysms (IAs) are severe cerebrovascular disorders lacking effective gene therapy or pharmacological interventions. Vascular smooth muscle cell (VSMC) senescence has been associated with various cardiovascular and cerebrovascular diseases; however, its role in IA pathogenesis remains unexplored, and the key regulatory genes remain unidentified. By integrating multi-omics data, machine learning, and experimental validation, we identified two senescence-associated genes (SAGs) that may serve as VSMC senescence biomarkers in IAs. We integrated single-cell RNA sequencing data from a mouse elastase-induced IA model (GSE193533) with human bulk RNA sequencing and microarray datasets to investigate VSMC senescence in IA. Our analyses included cell clustering, cell-cell communication, differential expression, functional enrichment, pseudotime trajectory inference, and high-dimensional weighted gene co-expression network analysis (hdWGCNA). Machine learning identified candidate SAGs, which were validated using external datasets and immunohistochemical analysis of human IA tissues. Single-cell analysis of the mouse IA model revealed 26 clusters across 10 cell types, with IA samples showing VSMC depletion, immune cell enrichment, and fibroblast expansion. VSMCs were categorized into five subsets (VSMC1-5), with the extracellular matrix remodeling and synthetic-inflammatory subtype (VSMC1) significantly increased. Differential expression analysis of VSMCs intersecting with senescence-associated genes from the Aging Atlas database identified 159 SAGs enriched in inflammatory and apoptotic pathways. Integrating hdWGCNA and bulk transcriptomics identified 45 key SAGs. TGFB1 and SERPINE1 emerged as robust biomarkers of senescence-associated VSMCs, showing high diagnostic accuracy (AUC > 0.75) and upregulation in IA tissues. Our study provides new insights into the pathological mechanisms of intracranial aneurysms. VSMC senescence may contribute to IA progression. TGFB1 and SERPINE1 may serve as biomarkers and promising therapeutic targets for VSMC senescence in IA. However, their specific mechanisms require further investigation and validation.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 1","pages":"24"},"PeriodicalIF":4.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150659","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}
Yuqian Tang, Yan Song, Qiuwen Sun, Muyuan Tong, Yejing Zhang, Yan Chen, Junyi Sha, Chengbin Xue, Jiabing Shen, Aihong Li
{"title":"Transplantation of Skin-Derived Precursor Schwann Cells Ameliorates Secondary Brain Injury after ICH in Mice by Activating the PI3K/AKT/FOXO3a Signaling Pathway.","authors":"Yuqian Tang, Yan Song, Qiuwen Sun, Muyuan Tong, Yejing Zhang, Yan Chen, Junyi Sha, Chengbin Xue, Jiabing Shen, Aihong Li","doi":"10.1007/s12975-026-01416-x","DOIUrl":"10.1007/s12975-026-01416-x","url":null,"abstract":"<p><p>This study investigated the therapeutic potential of skin-derived precursor Schwann cells (SKP-SCs) for secondary brain injury following intracerebral hemorrhage (ICH) and its underlying mechanisms. An ICH model was established in mice via intrastriatal autologous blood injection. SKP-SCs were administered intranasally 24 h post-ICH, with the AKT inhibitor GDC0068 used for intervention. Results demonstrated that transplanted SKP-SCs survived peri-hematomally, significantly improved short- and long-term neurological function, reduced brain tissue damage and neuronal apoptosis, preserved blood-brain barrier integrity, and suppressed microglial/macrophage activation and neutrophil infiltration. Mechanistically, SKP-SCs exerted neuroprotection by activating the PI3K/AKT/FOXO3a signaling pathway. In conclusion, intranasal SKP-SC transplantation alleviates ICH-induced deficits and secondary injury via this pathway, representing a promising therapeutic strategy during the acute phase following ICH.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 1","pages":"23"},"PeriodicalIF":4.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114123","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}
Maria E Ramos-Araque, Cristina Rodriguez, Rebeca Vecino, Elisa Cortijo Garcia, Mercedes de Lera Alfonso, Mercedes Sanchez Barba, Laura Colàs-Campàs, Francisco Purroy, Juan F Arenillas, Angeles Almeida, Maria Delgado-Esteban
{"title":"Correction to: The Neuronal Ischemic Tolerance Is Conditioned by the Tp53 Arg72Pro Polymorphism.","authors":"Maria E Ramos-Araque, Cristina Rodriguez, Rebeca Vecino, Elisa Cortijo Garcia, Mercedes de Lera Alfonso, Mercedes Sanchez Barba, Laura Colàs-Campàs, Francisco Purroy, Juan F Arenillas, Angeles Almeida, Maria Delgado-Esteban","doi":"10.1007/s12975-026-01417-w","DOIUrl":"10.1007/s12975-026-01417-w","url":null,"abstract":"","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 1","pages":"22"},"PeriodicalIF":4.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12864331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106970","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}
Min Li, Shijie Long, Mingxi Dang, Yaojing Chen, Zhanjun Zhang
{"title":"Identification of Brain Regions and Networks Critical to Poststroke Cognitive Impairment Through Lesion-symptom and Lesion Network Analyses.","authors":"Min Li, Shijie Long, Mingxi Dang, Yaojing Chen, Zhanjun Zhang","doi":"10.1007/s12975-026-01415-y","DOIUrl":"10.1007/s12975-026-01415-y","url":null,"abstract":"<p><p>Clarifying the critical lesion regions of poststroke cognitive impairment (PSCI) could improve the understanding of how anatomical locations and functional networks jointly influence the manifestation of cognitive deficits. Lesion-symptom and lesion network analyses are performed to identify the anatomical sites and functional networks related to specific cognitive functions. The multidomain cognitive statuses and the focal brain lesions of 83 patients with PSCI were recorded during the acute poststroke period (< 2 weeks). Multivariate lesion-symptom mapping was performed to identify risk regions, i.e., lesion sites associated with worse cognitive deficits; functional lesion network mapping was performed to identify risk networks, i.e., brain networks connected to risk regional peaks. Lesion-symptom mapping analysis identified several brain regions where lesions were significantly correlated with neurological deficit, general cognitive impairment, visuospatial dysfunction, and executive dysfunction. Various types of cognitive deficits presented diverse risk region distribution patterns with different peaks. Functional lesion network mapping demonstrated that networks connected to peak risk regions for neurological deficit and general cognitive impairment were mostly similar to the default network (DN), whereas the risk network for visuospatial and executive dysfunctions was the somatomotor network (SN). Functional imaging measurements directly from PSCI patients revealed that intranetwork functional connections within the limbic network, which is functionally similar to the DN, were stably reduced in all patients, and intranetwork functional connections in the SN exhibited the same pattern. Although the decreases did not present the network preference observed in lesion network mapping, these results still support the concept that lesions to specific nodes of the DN or SN are associated with the cognitive deficits that constitute PSCI.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 1","pages":"21"},"PeriodicalIF":4.2,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106997","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}
Michelle Lin, Mozammel Bhuiyan, Carly McCurry, Jessica Lamb, Marcio A Diniz, Karni Bedirian, Anil K Chauhan, Abhishek Jha, Aditi Jain, Enrique C Leira, Rakeshkumar Patel, Mohammad B Khan, Pradip Kamat, David C Hess, Krishnan Dhandapani, Huaxin Sheng, Sasha Zhang, Wei Yang, Bingren Hu, Chunli Liu, Lauren Sansing, Pinar Caglayan, Qinyue Guan, Ligia Boisserand, Cenk Ayata, Takahiko Imai, Kirsten Lynch, Patrick Lyden
{"title":"Feasibility of a Multi-Laboratory Model of Middle Cerebral Artery Thromboembolic Stroke with Thrombolysis: TE-MCAo.","authors":"Michelle Lin, Mozammel Bhuiyan, Carly McCurry, Jessica Lamb, Marcio A Diniz, Karni Bedirian, Anil K Chauhan, Abhishek Jha, Aditi Jain, Enrique C Leira, Rakeshkumar Patel, Mohammad B Khan, Pradip Kamat, David C Hess, Krishnan Dhandapani, Huaxin Sheng, Sasha Zhang, Wei Yang, Bingren Hu, Chunli Liu, Lauren Sansing, Pinar Caglayan, Qinyue Guan, Ligia Boisserand, Cenk Ayata, Takahiko Imai, Kirsten Lynch, Patrick Lyden","doi":"10.1007/s12975-025-01407-4","DOIUrl":"10.1007/s12975-025-01407-4","url":null,"abstract":"<p><p>No single animal stroke model satisfies all needs of translational stroke investigation. While the nylon filament model is widely accepted in preclinical translational stroke research, thromboembolic models have more physiological relevance. Thromboembolic models are technically difficult, time consuming, and show variable results, making them problematic for multi-laboratory preclinical network use. We sought to develop and validate a multi-laboratory thromboembolic middle cerebral artery occlusion model that encompasses vessel occlusion and subsequent thrombolysis. To reduce the numbers of donor animals used, we developed a method to store donor blood for later use. Using prefabricated microcatheters, we simplified thrombus preparation and handling. Emboli were prepared in microcatheters and injected directly into the middle cerebral artery from the internal carotid artery. For thrombolysis we used intravenous Tenecteplase dosing at 1.5 mg/kg. To demonstrate feasibility and ease-of-use, the model was implemented at six research laboratories. We wrote and field-tested standard operating procedures, training videos, and hands-on surgical training workshops. We enrolled 170 Sprague Dawley rats of both sexes at six laboratories who performed 4 to 6 thrombus embolizations per week. All sites could achieve reproducible occlusion and thrombolysis. Thromboemboli prepared from stored blood served as well as emboli from freshly drawn blood. Of 135 rats who received one embolus, 33 (24%) died before 48-hour MRI scan. In survivors, stroke volume was 13 ± 16% of the ipsilateral hemisphere. Occlusions were seen in the MCA in 15%, distal ICA in 19%, both (T-occlusions) in 2% and in the MCA/ACA in 1%. Corner test, neurobehavioral battery, and MRI showed reasonably consistent stroke injury. We established the feasibility and reproducibility of a multi-laboratory rodent thromboembolic model but further development is needed to improve the success rate and lower the mortality rate before this model can be accepted widely.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 1","pages":"20"},"PeriodicalIF":4.2,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12855246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146087297","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}
Janos Lückl, Monika Szücs, Ferenc Rarosi, Amirhossein Salehzadeh, Jens P Dreier
{"title":"Predictive Utility of Cerebral Blood Flow Transients in Experimental Stroke.","authors":"Janos Lückl, Monika Szücs, Ferenc Rarosi, Amirhossein Salehzadeh, Jens P Dreier","doi":"10.1007/s12975-025-01410-9","DOIUrl":"10.1007/s12975-025-01410-9","url":null,"abstract":"<p><p>A gap in developing novel preclinical treatment strategies for ischemic stroke is predicting long-term outcome in experimental stroke models early during ischemia to reduce heterogeneity and sample size. Besides saving costs through improved risk stratification, reducing the number of animals is a requirement of the 3Rs principle. In this secondary analysis, we analyzed 28 Sprague-Dawley rats of a prospective data base that underwent 90-minute filament-occlusion of the middle cerebral artery (MCAO) to assess the predictive power of early variables at 30, 60, and 90 min after occlusion. The animals were sacrificed after 72 h. Infarct sizes were determined by hematoxylin staining. In a minimally invasive fashion, we recorded cerebral blood flow (CBF) with laser-Doppler flowmetry and direct current (DC)/alternating current-electrocorticography (ECoG) with epidural Ag/AgCl electrodes. Both CBF and ECoG markers correlated with the cortical infarct volumes. Multiclass receiver operating characteristic analysis identified the best predictors of three risk classes, and Spearman's rank correlation was used to explore relationships between ECoG and CBF. The slope of the CBF transients in response to spreading depolarization (SD) was the best biomarker at all time points, while the DC integral was the best epidural biomarker. Both correlated negatively at all time points (ρ < -0.68). In summary, we have found that early risk stratification during MCAO in rats is possible using minimally invasive biomarkers. This would enable, in particular, the early sorting out of animals with a low risk of cortical infarction in neuroprotection studies, where these animals typically distort the statistical results.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 1","pages":"19"},"PeriodicalIF":4.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12823744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019657","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}
Basel Musmar, Joanna M Roy, Hammam Abdalrazeq, Celine Yacoub, Nimer Adeeb, Antony A Fuleihan, Sravanthi Koduri, Michael Baldassari, Matthews Lan, Pious Patel, Arbaz A Momin, Elias Atallah, Rabab Alshahrani, Spyridon Karadimas, Saman Sizdahkhani, Ajay Garg, Kareem El Naamani, Ching-Jen Chen, Roland Jabre, Hassan Saad, Jonathan A Grossberg, Adam A Dmytriw, Aman B Patel, Mirhojjat Khorasanizadeh, Christopher S Ogilvy, Ajith J Thomas, Andre Monteiro, Adnan Siddiqui, Gustavo M Cortez, Ricardo A Hanel, Rahim Abo Kasem, Guilherme Porto, Alejandro M Spiotta, Anthony J Piscopo, David M Hasan, Mohammad Ghorbani, Joshua Weinberg, Shahid M Nimjee, Kimon Bekelis, Mohamed M Salem, Jan-Karl Burkhardt, Akli Zetchi, Charles Matouk, Brian M Howard, Rosalind Lai, Rose Du, Rawad Abbas, Abdelaziz Amllay, Alfredo Munoz, Nabeel A Herial, Stavropoula I Tjoumakaris, Michael Reid Gooch, Christina Notarianni, Bharat Guthikonda, Jacques Morcos, Robert H Rosenwasser, Pascal Jabbour
{"title":"Outcomes of Bypass Surgery in Patients with Moyamoya Syndrome Secondary To Sickle Cell Disease: a Multicenter Study.","authors":"Basel Musmar, Joanna M Roy, Hammam Abdalrazeq, Celine Yacoub, Nimer Adeeb, Antony A Fuleihan, Sravanthi Koduri, Michael Baldassari, Matthews Lan, Pious Patel, Arbaz A Momin, Elias Atallah, Rabab Alshahrani, Spyridon Karadimas, Saman Sizdahkhani, Ajay Garg, Kareem El Naamani, Ching-Jen Chen, Roland Jabre, Hassan Saad, Jonathan A Grossberg, Adam A Dmytriw, Aman B Patel, Mirhojjat Khorasanizadeh, Christopher S Ogilvy, Ajith J Thomas, Andre Monteiro, Adnan Siddiqui, Gustavo M Cortez, Ricardo A Hanel, Rahim Abo Kasem, Guilherme Porto, Alejandro M Spiotta, Anthony J Piscopo, David M Hasan, Mohammad Ghorbani, Joshua Weinberg, Shahid M Nimjee, Kimon Bekelis, Mohamed M Salem, Jan-Karl Burkhardt, Akli Zetchi, Charles Matouk, Brian M Howard, Rosalind Lai, Rose Du, Rawad Abbas, Abdelaziz Amllay, Alfredo Munoz, Nabeel A Herial, Stavropoula I Tjoumakaris, Michael Reid Gooch, Christina Notarianni, Bharat Guthikonda, Jacques Morcos, Robert H Rosenwasser, Pascal Jabbour","doi":"10.1007/s12975-026-01412-1","DOIUrl":"10.1007/s12975-026-01412-1","url":null,"abstract":"<p><strong>Background: </strong>Moyamoya syndrome (MMS) associated with sickle cell disease (SCD) is a severe vasculopathy that significantly increases stroke risk. While cerebral revascularization is increasingly considered in this population, concerns about perioperative safety and long-term outcomes have limited its use in clinical practice.</p><p><strong>Methods: </strong>We conducted a multicenter, retrospective cohort study of 553 patients with MMS who underwent surgical revascularization across 13 centers. Patients were grouped by SCD status (SCD-MMS vs. moyamoya disease (MMD)). Primary outcomes included perioperative stroke, perioperative complications, and functional status at discharge. Secondary outcomes included length of stay, and follow-up stroke.</p><p><strong>Results: </strong>Of 553 patients, 32 (5.8%) had SCD. There were no significant differences in overall perioperative stroke (OR 1.05, 95% CI 0.19 to 5.54), symptomatic perioperative stroke (OR 0.94, 95% CI 0.09 to 8.94), perioperative complications (OR 1.66, 95% CI 0.47 to 5.86), or follow-up stroke (OR 0.88, 95% CI 0.17 to 4.55). Functional outcomes at discharge were similarly favorable in both groups (mRS 0-1: OR 0.84, 95% CI 0.29 to 2.40). SCD was associated with a longer hospital stay (beta 2.78 days, 95% CI 0.60 to 4.96).</p><p><strong>Conclusion: </strong>Surgical revascularization for MMS in patients with SCD does not confer additional procedural risk and yields outcomes comparable to those of patients without SCD. These findings support the role of bypass surgery as a viable treatment option in this high-risk population.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 1","pages":"18"},"PeriodicalIF":4.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012547","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}
Zixian Mei, Weijie Zhong, Tanjun Deng, Xuchen Meng, Xin Lv, Jiexi Xiao, Yi Li
{"title":"Recent Advances in Mitochondrial Transplantation for Ischemic Stroke: A Review of in Vitro and in Vivo Studies.","authors":"Zixian Mei, Weijie Zhong, Tanjun Deng, Xuchen Meng, Xin Lv, Jiexi Xiao, Yi Li","doi":"10.1007/s12975-025-01401-w","DOIUrl":"10.1007/s12975-025-01401-w","url":null,"abstract":"<p><p>Ischemic stroke is a common and devastating disease that imposes a huge burden on global health and the economy. Mitochondrial dysfunction is a key feature of cerebral ischemia-reperfusion injury (CIRI). Mitochondrial transplantation, an emerging neuroprotective strategy that introduces exogenous mitochondria into a living organism, has shown great potential in various neurological diseases. However, significant challenges persist, including the lack of standardized dosing regimens and unclear mechanisms regarding long-term mitochondrial engraftment. While initial clinical trials have demonstrated the safety of this approach, the field is currently at a pivotal juncture requiring rigorous translation from preclinical success to proven clinical efficacy. This review summarizes the in vitro and in vivo research findings on mitochondrial transplantation in stroke models, with the aim of providing a basis for the clinical translation of this technology.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 1","pages":"17"},"PeriodicalIF":4.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012558","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}
Katharina A M Hackenberg, Nicola Willett, Uwe Seibold, Gereon Weingarten, Rita Dreier, Natalija Pantelic, Amr Abdulazim, Gabriel J E Rinkel, Björn Wängler, Carmen Wängler, Nima Etminan
{"title":"Collagen Imaging in Human Intracranial Aneurysms - a Translational Proof-of-Concept Study.","authors":"Katharina A M Hackenberg, Nicola Willett, Uwe Seibold, Gereon Weingarten, Rita Dreier, Natalija Pantelic, Amr Abdulazim, Gabriel J E Rinkel, Björn Wängler, Carmen Wängler, Nima Etminan","doi":"10.1007/s12975-025-01403-8","DOIUrl":"10.1007/s12975-025-01403-8","url":null,"abstract":"<p><p>Unruptured intracranial aneurysms (IAs) are highly prevalent in the general population and there is an unmet need for radiological surrogates for the assessment of an increased risk of rupture. High turnover of type I collagen, i.e. abundant proportions of newly synthesized, immature collagen, has been linked to structural instability of the IA wall. This study aimed to test a newly synthesized positron emission tomography tracer that could selectively visualize immature type I collagen in human IAs as a marker for structural instability and thereby increased rupture risk. Following the synthesis of [<sup>68</sup>Ga]Ga-NODA-GA-PEG<sub>1</sub>-collagelin, in vitro and ex vivo analyses of collagen, nonhuman tissue and human IAs were performed. Patients undergoing microsurgical repair for unruptured and ruptured IAs were prospectively included in this cross-sectional, single-center study. After safe IA clipping and IA excision, cryosections of IAs were incubated with the tracer, and signal intensity was quantified via autoradiography. To differentiate immature from mature collagen, polarization microscopy was performed after picrosirius red staining. Our study showed that the synthesized tracer [<sup>68</sup>Ga]Ga-NODA-GA-PEG<sub>1</sub>-collagelin bound specifically to type I collagen in vitro and in rat tail tendon ex vivo. We included 25 patients with 25 IAs (12 unruptured, 13 ruptured). The tracer preferentially labeled immature type I collagen in human IAs ex vivo: Regions with high tracer uptake correlated with areas rich in immature collagen, as identified by polarization microscopy (r = 0.40, P = 0.002). [<sup>68</sup>Ga]Ga-NODA-GA-PEG<sub>1</sub>-collagelin could serve as a complementary, noninvasive molecular imaging tool for personalized assessment of IA instability, but animal studies are required before in vivo use of [<sup>68</sup>Ga]Ga-NODA-GA-PEG<sub>1</sub>-collagelin in humans.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 1","pages":"16"},"PeriodicalIF":4.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012574","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":"Association between Lipid Accumulation Product and 3-Month Functional Outcome after Ischemic Stroke: the Obesity-Stroke Paradox.","authors":"Yuan Ren, Ying Zhou, Tian-Yu Gu, Yang Cheng, Wei-Hua Wu, Xiao-Guang Dong, Feng-E Li, Yu-Sheng Zhang","doi":"10.1007/s12975-025-01396-4","DOIUrl":"10.1007/s12975-025-01396-4","url":null,"abstract":"<p><p>To explore the association of lipid accumulation product (LAP) with 3-month functional outcome and etiologic subtypes in patients with acute ischemic stroke. Patients with acute ischemic stroke admitted from July 1, 2020, to June 30, 2022 were enrolled in this study. Initial neurological severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) at admission. Functional outcome was evaluated by the modified Rankin Scale (mRS) at 3 months after ischemic stroke onset. Etiologic subtypes were determined according to the method reported in the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. LAP was calculated by a well-established formula and analyzed by quartiles (Q1-Q4). Multivariate logistic regression analysis was conducted to evaluate the association of LAP quartiles with 3-month functional outcome and etiologic subtypes in patients with acute ischemic stroke. A total of 431 patients with acute ischemic stroke were included in this study. After adjusting for several confounding factors, compared with those in the LAP-Q1 group, patients in LAP-Q3 and LAP-Q4 group had a reduced association with poor 3-month functional outcome [odds ratio (OR): 0.038, 95% confidence interval (CI): 0.004-0.339; OR: 0.014, 95% CI: 0.001-0.158]. Furthermore, patients in LAP-Q3 and LAP-Q4 group showed an increased association with Small-artery occlusion (SAO) subtype (OR: 1.919, 95% CI: 1.075-3.425; OR: 2.322, 95% CI: 1.265-4.262). Elevated LAP levels were associated with favorable 3-month functional outcome in patients with acute ischemic stroke, supporting the concept of the \"obesity-stroke paradox\". Concurrently, patients with elevated LAP levels were more likely to experience SAO as the etiological subtype of their stroke. </p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 1","pages":"15"},"PeriodicalIF":4.2,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967276","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}