Pub Date : 2025-12-17DOI: 10.1016/j.jstrokecerebrovasdis.2025.108529
Yangfang An , Biao Wang , Jiali Zhao , Hui Zhou , Qiong Zhou
Objective
Mitochondrial dysfunction is a key determinant of neuronal death and a promising therapeutic target in ischemic stroke. Dl-3-n-butylphthalide (NBP), an approved neuroprotective agent in China, has been shown to improve mitochondrial integrity, yet its precise molecular mechanisms remain unclear. This study aimed to determine whether NBP exerts neuroprotection by upregulating mitochondrial cytochrome c oxidase subunit 1 (MT-CO1) and to clarify the contribution of MT-CO1 to mitochondrial function recovery.
Methods
MT-CO1 expression was measured in the circulation from acute ischemic stroke participants before and following NBP therapy. In SH-SY5Y cells under OGD/R treatment, the action of NBP on mitochondrial bioenergetics, oxidative stress, and apoptosis were assessed. MT-CO1 knockdown was used to determine mechanistic involvement.
Results
NBP significantly increased MT-CO1 expression both in vivo and in vitro, improved mitochondrial membrane voltage and ATP production, reduced ROS generation, and decreased apoptosis. MT-CO1 silencing markedly attenuated these protective effects.
Conclusion
NBP protects against ischemia-induced mitochondrial dysfunction partly through MT-CO1 upregulation, supporting MT-CO1 as a potential therapeutic target for mitochondrial function protection in ischemic stroke.
{"title":"Dl-3-n-butylphthalide protects against ischemic stroke by enhancing mitochondrial function via MT-CO1 upregulation","authors":"Yangfang An , Biao Wang , Jiali Zhao , Hui Zhou , Qiong Zhou","doi":"10.1016/j.jstrokecerebrovasdis.2025.108529","DOIUrl":"10.1016/j.jstrokecerebrovasdis.2025.108529","url":null,"abstract":"<div><h3>Objective</h3><div>Mitochondrial dysfunction is a key determinant of neuronal death and a promising therapeutic target in ischemic stroke. Dl-3-n-butylphthalide (NBP), an approved neuroprotective agent in China, has been shown to improve mitochondrial integrity, yet its precise molecular mechanisms remain unclear. This study aimed to determine whether NBP exerts neuroprotection by upregulating mitochondrial cytochrome c oxidase subunit 1 (MT-CO1) and to clarify the contribution of MT-CO1 to mitochondrial function recovery.</div></div><div><h3>Methods</h3><div>MT-CO1 expression was measured in the circulation from acute ischemic stroke participants before and following NBP therapy. In SH-SY5Y cells under OGD/R treatment, the action of NBP on mitochondrial bioenergetics, oxidative stress, and apoptosis were assessed. MT-CO1 knockdown was used to determine mechanistic involvement.</div></div><div><h3>Results</h3><div>NBP significantly increased MT-CO1 expression both <em>in vivo</em> and <em>in vitro</em>, improved mitochondrial membrane voltage and ATP production, reduced ROS generation, and decreased apoptosis. MT-CO1 silencing markedly attenuated these protective effects.</div></div><div><h3>Conclusion</h3><div>NBP protects against ischemia-induced mitochondrial dysfunction partly through MT-CO1 upregulation, supporting MT-CO1 as a potential therapeutic target for mitochondrial function protection in ischemic stroke.</div></div>","PeriodicalId":54368,"journal":{"name":"Journal of Stroke & Cerebrovascular Diseases","volume":"35 2","pages":"Article 108529"},"PeriodicalIF":1.8,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comment on “synergistic impacts of physical activity and sleep on risk of dementia and all-cause mortality in Chinese older stroke survivors”","authors":"Bhumesh Tyagi MD , Leelabati Toppo MD , Aishwarya Biradar MD","doi":"10.1016/j.jstrokecerebrovasdis.2025.108526","DOIUrl":"10.1016/j.jstrokecerebrovasdis.2025.108526","url":null,"abstract":"","PeriodicalId":54368,"journal":{"name":"Journal of Stroke & Cerebrovascular Diseases","volume":"35 2","pages":"Article 108526"},"PeriodicalIF":1.8,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16DOI: 10.1016/j.jstrokecerebrovasdis.2025.108528
Ji Li , Yongjie Zhu , Jing Han , Zhenshan Wang , Hongbo Xue , Meili Zhai , Chong Liu
Background
With global population aging, the incidence of ischemic stroke is rising annually. However, its underlying mechanisms and effective clinical preventive and therapeutic measures remain elusive. This study investigated inflammatory mechanisms and therapeutic targets using a rat cerebral ischemia-reperfusion injury (CIRI) model, focusing on endoplasmic reticulum stress (ERS)-mediated inflammation.
Methods
A rat CIRI model was established. Neurological assessments were performed 24 h post-modeling. Histopathological analysis evaluated inflammatory cytokines (IL-1β, TNF-α) and NF-κB p65 nuclear translocation in the ischemic penumbra. Molecular profiling assessed activation of endoplasmic reticulum stress (ERS) markers (GRP78, p-PERK, p-eIF2α) and the ERS-associated transcription factor Glutamine-rich protein 1 (QRICH1). Pharmacological induction of ERS and treatment with berberine (BBR) were employed, with mechanistic studies including PERK inhibition.
Results
Neurological assessments revealed significant CIRI-induced neural deficits. Histopathology demonstrated upregulated IL-1β/TNF-α and NF-κB p65 nuclear translocation. Molecular profiling identified activation of ERS markers (GRP78, p-PERK, p-eIF2α) and a time-dependent elevation of QRICH1 post-CIRI. Pharmacological ERS induction confirmed QRICH1/PERK/NF-κB pathway activation. BBR administration significantly attenuated IL-1β/TNF-α levels, suppressed IκB-α degradation, and inhibited NF-κB nuclear translocation. Mechanistically, BBR downregulated QRICH1 upregulation and suppressed agonist-induced ERS-inflammatory cascades; these therapeutic effects were partially reversed by PERK inhibitor.
Conclusion
These findings propose modulation of the QRICH1-ERS pathway as a promising therapeutic target for CIRI management, with BBR conferring protection by partially suppressing this axis.
{"title":"Role of Qrich1-mediated endoplasmic reticulum stress pathway in Berberine inhibition of NF-κB activation induced by cerebral ischemia-reperfusion injury","authors":"Ji Li , Yongjie Zhu , Jing Han , Zhenshan Wang , Hongbo Xue , Meili Zhai , Chong Liu","doi":"10.1016/j.jstrokecerebrovasdis.2025.108528","DOIUrl":"10.1016/j.jstrokecerebrovasdis.2025.108528","url":null,"abstract":"<div><h3>Background</h3><div>With global population aging, the incidence of ischemic stroke is rising annually. However, its underlying mechanisms and effective clinical preventive and therapeutic measures remain elusive. This study investigated inflammatory mechanisms and therapeutic targets using a rat cerebral ischemia-reperfusion injury (CIRI) model, focusing on endoplasmic reticulum stress (ERS)-mediated inflammation.</div></div><div><h3>Methods</h3><div>A rat CIRI model was established. Neurological assessments were performed 24 h post-modeling. Histopathological analysis evaluated inflammatory cytokines (IL-1β, TNF-α) and NF-κB p65 nuclear translocation in the ischemic penumbra. Molecular profiling assessed activation of endoplasmic reticulum stress (ERS) markers (GRP78, p-PERK, p-eIF2α) and the ERS-associated transcription factor Glutamine-rich protein 1 (QRICH1). Pharmacological induction of ERS and treatment with berberine (BBR) were employed, with mechanistic studies including PERK inhibition.</div></div><div><h3>Results</h3><div>Neurological assessments revealed significant CIRI-induced neural deficits. Histopathology demonstrated upregulated IL-1β/TNF-α and NF-κB p65 nuclear translocation. Molecular profiling identified activation of ERS markers (GRP78, p-PERK, p-eIF2α) and a time-dependent elevation of QRICH1 post-CIRI. Pharmacological ERS induction confirmed QRICH1/PERK/NF-κB pathway activation. BBR administration significantly attenuated IL-1β/TNF-α levels, suppressed IκB-α degradation, and inhibited NF-κB nuclear translocation. Mechanistically, BBR downregulated QRICH1 upregulation and suppressed agonist-induced ERS-inflammatory cascades; these therapeutic effects were partially reversed by PERK inhibitor.</div></div><div><h3>Conclusion</h3><div>These findings propose modulation of the QRICH1-ERS pathway as a promising therapeutic target for CIRI management, with BBR conferring protection by partially suppressing this axis.</div></div>","PeriodicalId":54368,"journal":{"name":"Journal of Stroke & Cerebrovascular Diseases","volume":"35 2","pages":"Article 108528"},"PeriodicalIF":1.8,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1016/j.jstrokecerebrovasdis.2025.108525
Zijie Wang , Xinwei Zhao , Yan Ma
<div><h3>Introduction</h3><div>Stroke is a major acute cerebrovascular disorder and a leading cause of disability and death, for which ageing is a key risk factor. However, individuals of the same chronological age differ markedly in cerebrovascular vulnerability. This study aimed to investigate the association between biological aging and stroke risk and prognosis using several validated aging metrics.</div></div><div><h3>Methods</h3><div>In NHANES 1999–2018, we derived the frailty index (FI), Klemera–Doubal age (KDMAge) and phenotypic age (PhenoAge) as alternative measures of biological aging. Logistic regression, tests for trend, restricted cubic splines and subgroup analyses were used to assess associations with stroke prevalence. Kaplan–Meier curves and Cox regression were applied to evaluate all-cause mortality among stroke survivors. In parallel, we conducted bidirectional two-sample Mendelian randomization (MR) using large genome-wide association studies to examine the potential causal effects of multiple biological aging indicators (four epigenetic age acceleration measures, telomere length, facial aging and FI) on stroke and its ischaemic subtypes, and the reverse effects of stroke on aging acceleration.</div></div><div><h3>Results</h3><div>Among 34,856 participants, higher FI, KDMAge and PhenoAge, as well as biological age acceleration, were associated with increased stroke risk; these associations remained significant in fully adjusted models. Dose–response analyses revealed non-linear relationships between biological aging metrics and stroke, with FI and PhenoAge showing J-shaped and KDMAge S-shaped patterns. In survival analyses of 1,167 stroke patients, PhenoAge acceleration and frailty status were significantly associated with reduced survival probability and higher all-cause mortality, whereas KDMAge acceleration showed weaker prognostic value. In MR analyses meta-analysing GIGASTROKE and MEGASTROKE, genetically predicted FI was associated with higher risk of stroke overall (OR = 1.57, 95 % CI: 1.36–1.83, <em>p</em> < 0.001) and with major ischaemic subtypes, while other aging clocks showed weaker or subtype-specific associations. Reverse MR indicated that stroke liability was associated with higher PhenoAge acceleration (OR = 1.54, 95 % CI: 1.12–2.12, <em>p</em> = 0.008), higher FI (OR = 1.11, 95 % CI: 1.05–1.17, <em>p</em> < 0.001) and accelerated facial aging (OR = 1.02, 95 % CI: 1.01–1.03, <em>p</em> = 0.001).</div></div><div><h3>Conclusion</h3><div>In a nationally representative sample, multiple biological aging indicators were associated with stroke and post-stroke all-cause mortality, and bidirectional MR supported a potential two-way relationship between biological aging and stroke. Among the evaluated metrics, FI showed the most robust and consistent associations with stroke risk and survival and provided the clearest and most stable genetic evidence compatible with a causal effect on stroke and its ischaemic subty
中风是一种主要的急性脑血管疾病，是致残和死亡的主要原因，其中衰老是一个关键的危险因素。然而，相同年龄的个体在脑血管易损性方面存在显著差异。本研究旨在通过几个有效的衰老指标来研究生物衰老与卒中风险和预后之间的关系。方法在NHANES 1999-2018中，我们导出了脆性指数（FI）、klemera - double年龄（KDMAge）和表型年龄（PhenoAge）作为生物衰老的替代指标。采用Logistic回归、趋势检验、受限三次样条和亚组分析来评估与卒中患病率的关系。应用Kaplan-Meier曲线和Cox回归评价脑卒中幸存者的全因死亡率。与此同时，我们利用大型全基因组关联研究进行了双向双样本孟德尔随机化（MR），以检验多种生物衰老指标（四种表观遗传年龄加速指标、端粒长度、面部衰老和FI）对中风及其缺血性亚型的潜在因果影响，以及中风对衰老加速的反向影响。结果在34,856名参与者中，较高的FI、KDMAge和PhenoAge以及生物年龄加速与卒中风险增加相关；这些关联在完全调整后的模型中仍然显著。剂量-反应分析显示生物老化指标与中风之间存在非线性关系，FI和PhenoAge呈j型，kdage呈s型。在1167例脑卒中患者的生存分析中，表型age加速和虚弱状态与生存率降低和全因死亡率升高显著相关，而KDMAge加速显示出较弱的预后价值。在对GIGASTROKE和MEGASTROKE进行的MR荟萃分析中，基因预测的FI与卒中总体风险较高（OR = 1.57, 95% CI: 1.36-1.83, p < 0.001）和主要缺血亚型相关，而其他衰老时钟显示较弱或亚型特异性关联。反向MR显示卒中易感性与较高的表型加速（OR = 1.54, 95% CI: 1.12-2.12, p = 0.008）、较高的FI （OR = 1.11, 95% CI: 1.05-1.17, p < 0.001）和面部加速老化（OR = 1.02, 95% CI: 1.01-1.03, p = 0.001）相关。结论：在一个具有全国代表性的样本中，多种生物衰老指标与脑卒中和脑卒中后全因死亡率相关，双向磁共振支持生物衰老与脑卒中之间潜在的双向关系。在评估的指标中，FI显示出与卒中风险和生存最强大和一致的关联，并提供了最清晰和最稳定的遗传证据，与卒中及其缺血性亚型的因果效应相一致。这些发现支持FI作为在卒中风险分层和二级预防中捕获生物衰老的实用工具，这一主张值得在前瞻性和介入性研究中进行测试。
{"title":"Association between biological aging and stroke and all-cause mortality: A population-based cross-sectional study and Mendelian randomization analysis","authors":"Zijie Wang , Xinwei Zhao , Yan Ma","doi":"10.1016/j.jstrokecerebrovasdis.2025.108525","DOIUrl":"10.1016/j.jstrokecerebrovasdis.2025.108525","url":null,"abstract":"<div><h3>Introduction</h3><div>Stroke is a major acute cerebrovascular disorder and a leading cause of disability and death, for which ageing is a key risk factor. However, individuals of the same chronological age differ markedly in cerebrovascular vulnerability. This study aimed to investigate the association between biological aging and stroke risk and prognosis using several validated aging metrics.</div></div><div><h3>Methods</h3><div>In NHANES 1999–2018, we derived the frailty index (FI), Klemera–Doubal age (KDMAge) and phenotypic age (PhenoAge) as alternative measures of biological aging. Logistic regression, tests for trend, restricted cubic splines and subgroup analyses were used to assess associations with stroke prevalence. Kaplan–Meier curves and Cox regression were applied to evaluate all-cause mortality among stroke survivors. In parallel, we conducted bidirectional two-sample Mendelian randomization (MR) using large genome-wide association studies to examine the potential causal effects of multiple biological aging indicators (four epigenetic age acceleration measures, telomere length, facial aging and FI) on stroke and its ischaemic subtypes, and the reverse effects of stroke on aging acceleration.</div></div><div><h3>Results</h3><div>Among 34,856 participants, higher FI, KDMAge and PhenoAge, as well as biological age acceleration, were associated with increased stroke risk; these associations remained significant in fully adjusted models. Dose–response analyses revealed non-linear relationships between biological aging metrics and stroke, with FI and PhenoAge showing J-shaped and KDMAge S-shaped patterns. In survival analyses of 1,167 stroke patients, PhenoAge acceleration and frailty status were significantly associated with reduced survival probability and higher all-cause mortality, whereas KDMAge acceleration showed weaker prognostic value. In MR analyses meta-analysing GIGASTROKE and MEGASTROKE, genetically predicted FI was associated with higher risk of stroke overall (OR = 1.57, 95 % CI: 1.36–1.83, <em>p</em> < 0.001) and with major ischaemic subtypes, while other aging clocks showed weaker or subtype-specific associations. Reverse MR indicated that stroke liability was associated with higher PhenoAge acceleration (OR = 1.54, 95 % CI: 1.12–2.12, <em>p</em> = 0.008), higher FI (OR = 1.11, 95 % CI: 1.05–1.17, <em>p</em> < 0.001) and accelerated facial aging (OR = 1.02, 95 % CI: 1.01–1.03, <em>p</em> = 0.001).</div></div><div><h3>Conclusion</h3><div>In a nationally representative sample, multiple biological aging indicators were associated with stroke and post-stroke all-cause mortality, and bidirectional MR supported a potential two-way relationship between biological aging and stroke. Among the evaluated metrics, FI showed the most robust and consistent associations with stroke risk and survival and provided the clearest and most stable genetic evidence compatible with a causal effect on stroke and its ischaemic subty","PeriodicalId":54368,"journal":{"name":"Journal of Stroke & Cerebrovascular Diseases","volume":"35 2","pages":"Article 108525"},"PeriodicalIF":1.8,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145771990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-12DOI: 10.1016/j.jstrokecerebrovasdis.2025.108524
Weichen Liu , Ben Shifflett , Teri McQuaid , Marissa D’Souza , Reza Bavarsad Shahripour , Kunal Agrawal , Dawn M. Meyer , Derek Dutt , Dale Keehan , Nadir Weibel , Brett C. Meyer
Background
Telestroke allows care irrespective of distance but has limitations in degree of immersive interaction. Augmented Reality (AR) holds promise, enabling providers and patients to interact as if in the same physical space. Prior investigations have shown immersive satisfaction for Holo-Stroke allowing 3D hologram providers to be transmitted to distant sites, and allowing for hologram assessments of Large Vessel Occlusions (LVOs).
Methods
We presented 2 evaluation techniques (both telestroke and Holo-Stroke) to a group of stroke service inpatients. Three optical cameras with depth sensing capability were placed around the stroke provider, with imaging streams transmitted in real-time via intranet to a HoloLens 2 Head-Mounted-Display (HMD) worn by patient at a distant site. The provider was visualized in the patient’s room as a hologram. Sample MRI, CTA, NIHSS picture card, and animation video were also visible to the patient through the HMD. Satisfaction questions were assessed via Likert scale. Wilcoxon Signed Rank, and Exact Binomial Test were used.
Results
Twenty inpatients with deficits consistent with acute stroke participated. Median age was 68 years, 45 % were female, 55 % white, and 20 % Hispanic. Median Likert scores favored Holo-Stroke over telestroke overall (47(93 %) vs 25.5(48 %);p < 0.001), and for immersion (10(92 %) vs 4(37 %);p < 0.001), beneficial technique (10(95 %) vs 5.5(55 %);p < 0.001), and seeing images (10(97 %) vs 5(45 %);p < 0.001). Clinical observations were overwhelmingly favorable.
Discussion
This Holo-Stroke telestroke, assessing acute stroke patients in the inpatient setting using wireless 3D hologram technique, resulted in robust immersion and significant increase in patient satisfaction. Although future evaluations of Holo-Stroke in acute telestroke are still warranted, Holo-Stroke has now clearly been shown to improve inpatient immersion and satisfaction.
{"title":"Holo-Stroke-ii: Stroke care through stroke hologram teleportation- inpatient immersion","authors":"Weichen Liu , Ben Shifflett , Teri McQuaid , Marissa D’Souza , Reza Bavarsad Shahripour , Kunal Agrawal , Dawn M. Meyer , Derek Dutt , Dale Keehan , Nadir Weibel , Brett C. Meyer","doi":"10.1016/j.jstrokecerebrovasdis.2025.108524","DOIUrl":"10.1016/j.jstrokecerebrovasdis.2025.108524","url":null,"abstract":"<div><h3>Background</h3><div>Telestroke allows care irrespective of distance but has limitations in degree of immersive interaction. Augmented Reality (AR) holds promise, enabling providers and patients to interact as if in the same physical space. Prior investigations have shown immersive satisfaction for Holo-Stroke allowing 3D hologram providers to be transmitted to distant sites, and allowing for hologram assessments of Large Vessel Occlusions (LVOs).</div></div><div><h3>Methods</h3><div>We presented 2 evaluation techniques (both telestroke and Holo-Stroke) to a group of stroke service inpatients. Three optical cameras with depth sensing capability were placed around the stroke provider, with imaging streams transmitted in real-time via intranet to a HoloLens 2 Head-Mounted-Display (HMD) worn by patient at a distant site. The provider was visualized in the patient’s room as a hologram. Sample MRI, CTA, NIHSS picture card, and animation video were also visible to the patient through the HMD. Satisfaction questions were assessed via Likert scale. Wilcoxon Signed Rank, and Exact Binomial Test were used.</div></div><div><h3>Results</h3><div>Twenty inpatients with deficits consistent with acute stroke participated. Median age was 68 years, 45 % were female, 55 % white, and 20 % Hispanic. Median Likert scores favored Holo-Stroke over telestroke overall (47(93 %) vs 25.5(48 %);<em>p</em> < 0.001), and for immersion (10(92 %) vs 4(37 %);<em>p</em> < 0.001), beneficial technique (10(95 %) vs 5.5(55 %);<em>p</em> < 0.001), and seeing images (10(97 %) vs 5(45 %);<em>p</em> < 0.001). Clinical observations were overwhelmingly favorable.</div></div><div><h3>Discussion</h3><div>This Holo-Stroke telestroke, assessing acute stroke patients in the inpatient setting using wireless 3D hologram technique, resulted in robust immersion and significant increase in patient satisfaction. Although future evaluations of Holo-Stroke in acute telestroke are still warranted, Holo-Stroke has now clearly been shown to improve inpatient immersion and satisfaction.</div></div>","PeriodicalId":54368,"journal":{"name":"Journal of Stroke & Cerebrovascular Diseases","volume":"35 1","pages":"Article 108524"},"PeriodicalIF":1.8,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.1016/j.jstrokecerebrovasdis.2025.108523
Oscar H. Del Brutto MD , Robertino M. Mera MD, PhD , Aldo F. Costa MD , Denisse A. Rumbea MHA , Emilio E. Arias MD , Víctor J. Del Brutto MD, MS
Background and aims
Carotid siphon calcifications (CSC) are recognized markers of cerebrovascular aging and vascular injury. Despite their relevance, longitudinal data on CSC progression is limited. In this study, we evaluated factors associated with CSC progression in middle-aged and older adults.
Methods
We conducted a prospective cohort study in a rural Ecuadorian population, assessing CSC progression using non-enhanced CT scans carried out an average of 7.4 years apart. CSC were graded using Woodcock’s scale (absent, mild, moderate, and severe), with progression defined as an increase of ≥1 grade in the follow-up CT. Poisson and multinomial logistic regression models assessed associations between CSC progression and baseline demographics and cardiovascular risk factors.
Results
The study included 396 individuals aged ≥40 years (mean age: 57.5±11.2 years; 45% women). At baseline, 236 (60%) participants had absent; 87 (22%) mild; and 73 (18%) moderate CSC. Follow-up CTs revealed CSC progression in 17 (4.3%) participants, with an overall rate of 0.78 events per 100 person-years. Smoking (IRR: 3.83; 95% C.I.: 1.3–11.3) and arterial hypertension (IRR: 3.67; 95% CI: 1.5–8.63) emerged as the strongest modifiable predictors of CSC progression. Participants with a poor smoking status showed a progression of 2.61 events per 100 person-years versus 0.68 in non-smokers. Hypertensives had a progression rate of 1.51 events versus 0.41 in normotensives.
Conclusions
CSC may progress over time – albeit slowly – in individuals with advancing age, smoking history, and hypertension. The low rate of progression suggests that routine CT-based monitoring is unlikely to be justified in clinical practice. Instead, our findings highlight the importance of controlling modifiable risk factors to mitigate vascular injury.
{"title":"Longitudinal characterization of carotid siphon calcifications: A CT-based population study","authors":"Oscar H. Del Brutto MD , Robertino M. Mera MD, PhD , Aldo F. Costa MD , Denisse A. Rumbea MHA , Emilio E. Arias MD , Víctor J. Del Brutto MD, MS","doi":"10.1016/j.jstrokecerebrovasdis.2025.108523","DOIUrl":"10.1016/j.jstrokecerebrovasdis.2025.108523","url":null,"abstract":"<div><h3>Background and aims</h3><div>Carotid siphon calcifications (CSC) are recognized markers of cerebrovascular aging and vascular injury. Despite their relevance, longitudinal data on CSC progression is limited. In this study, we evaluated factors associated with CSC progression in middle-aged and older adults.</div></div><div><h3>Methods</h3><div>We conducted a prospective cohort study in a rural Ecuadorian population, assessing CSC progression using non-enhanced CT scans carried out an average of 7.4 years apart. CSC were graded using Woodcock’s scale (absent, mild, moderate, and severe), with progression defined as an increase of ≥1 grade in the follow-up CT. Poisson and multinomial logistic regression models assessed associations between CSC progression and baseline demographics and cardiovascular risk factors.</div></div><div><h3>Results</h3><div>The study included 396 individuals aged ≥40 years (mean age: 57.5±11.2 years; 45% women). At baseline, 236 (60%) participants had absent; 87 (22%) mild; and 73 (18%) moderate CSC. Follow-up CTs revealed CSC progression in 17 (4.3%) participants, with an overall rate of 0.78 events per 100 person-years. Smoking (IRR: 3.83; 95% C.I.: 1.3–11.3) and arterial hypertension (IRR: 3.67; 95% CI: 1.5–8.63) emerged as the strongest modifiable predictors of CSC progression. Participants with a poor smoking status showed a progression of 2.61 events per 100 person-years <em>versus</em> 0.68 in non-smokers. Hypertensives had a progression rate of 1.51 events <em>versus</em> 0.41 in normotensives.</div></div><div><h3>Conclusions</h3><div>CSC may progress over time – albeit slowly – in individuals with advancing age, smoking history, and hypertension. The low rate of progression suggests that routine CT-based monitoring is unlikely to be justified in clinical practice. Instead, our findings highlight the importance of controlling modifiable risk factors to mitigate vascular injury.</div></div>","PeriodicalId":54368,"journal":{"name":"Journal of Stroke & Cerebrovascular Diseases","volume":"35 1","pages":"Article 108523"},"PeriodicalIF":1.8,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.1016/j.jstrokecerebrovasdis.2025.108521
Jiawen Wei, Yan Shen
Background
Physical activity (PA) and sleep reduce the risk of dementia and mortality, but evidence among older stroke survivors in China is limited.
Objective
To investigate the impact of PA on dementia and all-cause mortality risks in this population and analyze its joint effect with sleep.
Methods
Utilizing data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), we analyzed the correlation of PA with dementia and mortality in elderly stroke survivors and explored the mediating role of dementia in the PA–mortality relationship. Joint variables of PA and sleep were constructed to assess their combined effects on dementia and mortality.
Results
Older stroke survivors engaging in regular PA had a 38 % reduced risk of dementia [Odds Ratio (OR) =0.62, 95 % Confidence Interval (CI): 0.56-0.69, P < 0.001] and a 44 % lower risk of mortality [Hazard Ratio (HR) =0.56, 95 % CI: 0.52-0.59, P < 0.001]. Additional protective factors against dementia included pet ownership, social activity, and reading, whereas television viewing and radio listening were linked to an increased risk of dementia. Raising domestic animals/pets, participating in outdoor activities, and performing housework were associated with a lower mortality risk (P < 0.05). Dementia mediated 5.9 % of PA–mortality risk relationship. The joint analysis highlighted that coupling regular PA with sleep exceeding 9 h was associated with a 42 % decrease in dementia risk, whereas pairing it with 9 h or less of sleep yielded a 60 % decrease in mortality risk.
Conclusion
For elderly stroke survivors, PA confers protective effects against both dementia and all-cause mortality. This association is partially mediated by the reduced risk of dementia. Furthermore, the beneficial impact of regular PA on these outcomes is moderated by sleep duration, underscoring the necessity of a joint consideration of both factors in prognostic assessments. This study underscores the importance of adopting an integrative perspective to assess exercise, daily activities, and sleep in stroke survivor prognosis. Our findings provide critical evidence for developing individualized, non-pharmacological, comprehensive management strategies and indicate future directions for interventional research.
{"title":"Synergistic impacts of physical activity and sleep on risk of dementia and all-cause mortality in Chinese older stroke survivors","authors":"Jiawen Wei, Yan Shen","doi":"10.1016/j.jstrokecerebrovasdis.2025.108521","DOIUrl":"10.1016/j.jstrokecerebrovasdis.2025.108521","url":null,"abstract":"<div><h3>Background</h3><div>Physical activity (PA) and sleep reduce the risk of dementia and mortality, but evidence among older stroke survivors in China is limited.</div></div><div><h3>Objective</h3><div>To investigate the impact of PA on dementia and all-cause mortality risks in this population and analyze its joint effect with sleep.</div></div><div><h3>Methods</h3><div>Utilizing data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), we analyzed the correlation of PA with dementia and mortality in elderly stroke survivors and explored the mediating role of dementia in the PA–mortality relationship. Joint variables of PA and sleep were constructed to assess their combined effects on dementia and mortality.</div></div><div><h3>Results</h3><div>Older stroke survivors engaging in regular PA had a 38 % reduced risk of dementia [Odds Ratio (OR) =0.62, 95 % Confidence Interval (CI): 0.56-0.69, <em>P</em> < 0.001] and a 44 % lower risk of mortality [Hazard Ratio (HR) =0.56, 95 % CI: 0.52-0.59, <em>P</em> < 0.001]. Additional protective factors against dementia included pet ownership, social activity, and reading, whereas television viewing and radio listening were linked to an increased risk of dementia. Raising domestic animals/pets, participating in outdoor activities, and performing housework were associated with a lower mortality risk (<em>P</em> < 0.05). Dementia mediated 5.9 % of PA–mortality risk relationship. The joint analysis highlighted that coupling regular PA with sleep exceeding 9 h was associated with a 42 % decrease in dementia risk, whereas pairing it with 9 h or less of sleep yielded a 60 % decrease in mortality risk.</div></div><div><h3>Conclusion</h3><div>For elderly stroke survivors, PA confers protective effects against both dementia and all-cause mortality. This association is partially mediated by the reduced risk of dementia. Furthermore, the beneficial impact of regular PA on these outcomes is moderated by sleep duration, underscoring the necessity of a joint consideration of both factors in prognostic assessments. This study underscores the importance of adopting an integrative perspective to assess exercise, daily activities, and sleep in stroke survivor prognosis. Our findings provide critical evidence for developing individualized, non-pharmacological, comprehensive management strategies and indicate future directions for interventional research.</div></div>","PeriodicalId":54368,"journal":{"name":"Journal of Stroke & Cerebrovascular Diseases","volume":"35 2","pages":"Article 108521"},"PeriodicalIF":1.8,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-10DOI: 10.1016/j.jstrokecerebrovasdis.2025.108522
Karim Borei MD , Abdulaziz T. Bako PhD MPH MBBS , Alan P. Pan MS , Osman Khan BS , Gavin W. Britz MD MPH MBA , Farhaan S. Vahidy PhD MBBS MPH , Thomas B.H. Potter PhD
Introduction
Cerebral Small Vessel Disease (CSVD) is associated with cognitive disruptions after intracerebral hemorrhage (ICH), however evidence connecting CSVD to admission National Institutes of Health Stroke Scale (NIHSS) scores is limited.
Methods
Electronic medical record data were retrieved for adult patients (>18 years) with admission for primary ICH and available NIHSS and CSVD assessment. CSVD burden was graded from 0 to 4 based on magnetic resonance imaging, with 1 point assessed for: 1) deep Fazekas score of 2-3 or periventricular (PV) Fazekas score of 3; 2) cerebral microbleed presence; 3) lacune presence; 4) > 20 basal ganglia perivascular spaces. Severe CSVD was defined as a summary score ≥ 3, and individual marker severity was assessed using the same criteria. The primary outcome was moderate-severe stroke (total NIHSS score ≥5). Secondary outcomes were severe motor deficit (motor score >12), complete aphasia (language score = 3), and cortical deficit (any impairment in language, extinction, and gaze). Associations between CSVD and NIHSS were determined using multivariable logistic regression, adjusting for major clinical and demographic factors. Adjusted odds ratios (aOR) and 95 % confidence interval (CI) are reported.
Results
The cohort included 1024 patients (median age [interquartile range]: 71 [61-79], 53 % male). Patients were 43 % White, 23 % Black, 21 % Hispanic, 8 % Asian, 5 % other; 477 (47 %) showed moderate-severe NIHSS scores and 262 (26 %) showed severe CSVD. Periventricular white matter hyperintensity (WMH) burden was independently associated with moderate-severe NIHSS score (aOR, 95 % CI: 1.54, [1.02-2.33]). Deep WMH burden was independently associated with aphasia (2.02, [1.03-3.91]), and motor deficit (3.64, [1.15-12.19]).
Conclusion
Severe WMH burdens independently increase odds of neurological deficit among patients with primary ICH.
{"title":"Cerebral small vessel disease characteristics associate with domain-specific impairments during Intracerebral Hemorrhage: A retrospective cohort study","authors":"Karim Borei MD , Abdulaziz T. Bako PhD MPH MBBS , Alan P. Pan MS , Osman Khan BS , Gavin W. Britz MD MPH MBA , Farhaan S. Vahidy PhD MBBS MPH , Thomas B.H. Potter PhD","doi":"10.1016/j.jstrokecerebrovasdis.2025.108522","DOIUrl":"10.1016/j.jstrokecerebrovasdis.2025.108522","url":null,"abstract":"<div><h3>Introduction</h3><div>Cerebral Small Vessel Disease (CSVD) is associated with cognitive disruptions after intracerebral hemorrhage (ICH), however evidence connecting CSVD to admission National Institutes of Health Stroke Scale (NIHSS) scores is limited.</div></div><div><h3>Methods</h3><div>Electronic medical record data were retrieved for adult patients (>18 years) with admission for primary ICH and available NIHSS and CSVD assessment. CSVD burden was graded from 0 to 4 based on magnetic resonance imaging, with 1 point assessed for: 1) deep Fazekas score of 2-3 or periventricular (PV) Fazekas score of 3; 2) cerebral microbleed presence; 3) lacune presence; 4) > 20 basal ganglia perivascular spaces. Severe CSVD was defined as a summary score ≥ 3, and individual marker severity was assessed using the same criteria. The primary outcome was moderate-severe stroke (total NIHSS score ≥5). Secondary outcomes were severe motor deficit (motor score >12), complete aphasia (language score = 3), and cortical deficit (any impairment in language, extinction, and gaze). Associations between CSVD and NIHSS were determined using multivariable logistic regression, adjusting for major clinical and demographic factors. Adjusted odds ratios (aOR) and 95 % confidence interval (CI) are reported.</div></div><div><h3>Results</h3><div>The cohort included 1024 patients (median age [interquartile range]: 71 [61-79], 53 % male). Patients were 43 % White, 23 % Black, 21 % Hispanic, 8 % Asian, 5 % other; 477 (47 %) showed moderate-severe NIHSS scores and 262 (26 %) showed severe CSVD. Periventricular white matter hyperintensity (WMH) burden was independently associated with moderate-severe NIHSS score (aOR, 95 % CI: 1.54, [1.02-2.33]). Deep WMH burden was independently associated with aphasia (2.02, [1.03-3.91]), and motor deficit (3.64, [1.15-12.19]).</div></div><div><h3>Conclusion</h3><div>Severe WMH burdens independently increase odds of neurological deficit among patients with primary ICH.</div></div>","PeriodicalId":54368,"journal":{"name":"Journal of Stroke & Cerebrovascular Diseases","volume":"35 1","pages":"Article 108522"},"PeriodicalIF":1.8,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-10DOI: 10.1016/j.jstrokecerebrovasdis.2025.108520
Wei Li, Lei Shi
{"title":"Letter to the editor: Acupuncture combined with repetitive transcranial magnetic stimulation for enhancing cortical excitability in the lesional hemisphere after ischemic stroke: A systematic review and meta-analysis","authors":"Wei Li, Lei Shi","doi":"10.1016/j.jstrokecerebrovasdis.2025.108520","DOIUrl":"10.1016/j.jstrokecerebrovasdis.2025.108520","url":null,"abstract":"","PeriodicalId":54368,"journal":{"name":"Journal of Stroke & Cerebrovascular Diseases","volume":"35 2","pages":"Article 108520"},"PeriodicalIF":1.8,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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