Pub Date : 2025-08-01Epub Date: 2025-06-09DOI: 10.1016/j.hest.2025.05.001
Ozal Beylerli , Leili Gulieva , Valentin Pavlov , Huaizhang Shi
Gliomas are among the most prevalent primary intracranial malignancies, and their management remains complex due to high rates of morbidity and mortality. Hemorrhage within gliomas, although relatively uncommon, can exacerbate disease progression, complicate clinical decision-making, and worsen patient outcomes. Identifying reliable, non-invasive biomarkers that predict or detect hemorrhage risk in glioma is an emerging research priority. This review examines the current landscape of non-invasive biomarkers—including advanced neuroimaging parameters, circulating molecular signatures, and genetic markers—that have shown potential in identifying glioma hemorrhage. We begin by summarizing the mechanisms and risk factors underlying hemorrhagic events in glioma, emphasizing the pathophysiological interplay between tumor angiogenesis, microvascular fragility, and coagulopathies. We then explore the role of modern neuroimaging techniques, such as susceptibility-weighted imaging (SWI), dynamic contrast-enhanced MRI, and radiomic-based analytical models, in uncovering hemodynamic and structural features predictive of hemorrhage. Concurrently, we evaluate key circulating biomarkers—ranging from cell-free DNA to microRNAs and extracellular vesicles—that hold promise for real-time, minimally invasive assessment of vascular integrity. By synthesizing evidence from these domains, we highlight their individual strengths and limitations and propose an integrative strategy that combines imaging and liquid biopsy approaches for enhanced diagnostic accuracy. Collectively, this review aims to provide clinicians and researchers with a comprehensive understanding of the utility and prospects of non-invasive biomarkers in the context of glioma hemorrhage, ultimately guiding more personalized surveillance and therapeutic interventions.
{"title":"Identification of non-invasive biomarkers associated with glioma hemorrhage","authors":"Ozal Beylerli , Leili Gulieva , Valentin Pavlov , Huaizhang Shi","doi":"10.1016/j.hest.2025.05.001","DOIUrl":"10.1016/j.hest.2025.05.001","url":null,"abstract":"<div><div>Gliomas are among the most prevalent primary intracranial malignancies, and their management remains complex due to high rates of morbidity and mortality. Hemorrhage within gliomas, although relatively uncommon, can exacerbate disease progression, complicate clinical decision-making, and worsen patient outcomes. Identifying reliable, non-invasive biomarkers that predict or detect hemorrhage risk in glioma is an emerging research priority. This review examines the current landscape of non-invasive biomarkers—including advanced neuroimaging parameters, circulating molecular signatures, and genetic markers—that have shown potential in identifying glioma hemorrhage. We begin by summarizing the mechanisms and risk factors underlying hemorrhagic events in glioma, emphasizing the pathophysiological interplay between tumor angiogenesis, microvascular fragility, and coagulopathies. We then explore the role of modern neuroimaging techniques, such as susceptibility-weighted imaging (SWI), dynamic contrast-enhanced MRI, and radiomic-based analytical models, in uncovering hemodynamic and structural features predictive of hemorrhage. Concurrently, we evaluate key circulating biomarkers—ranging from cell-free DNA to microRNAs and extracellular vesicles—that hold promise for real-time, minimally invasive assessment of vascular integrity. By synthesizing evidence from these domains, we highlight their individual strengths and limitations and propose an integrative strategy that combines imaging and liquid biopsy approaches for enhanced diagnostic accuracy. Collectively, this review aims to provide clinicians and researchers with a comprehensive understanding of the utility and prospects of non-invasive biomarkers in the context of glioma hemorrhage, ultimately guiding more personalized surveillance and therapeutic interventions.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 4","pages":"Pages 176-187"},"PeriodicalIF":1.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2024-11-16DOI: 10.1016/j.hest.2024.11.001
Bing-Qiao Wang , Yu-Fan Ma , Guo-Qing Zhang , Ke Yan , Yan-Yun Wang , Qin Zhang , Lan Chen , Chen-Hao Zhao , Sen Lin , Qing-Wu Yang
Hypertension is a major cause of cerebral hemorrhage. Although they are widely used in preclinical studies on cerebral hemorrhage, traditional in vivo cerebrovascular imaging techniques, such as positron emission tomography and magnetic resonance imaging, often fall short in dynamically visualizing cerebral microcirculation blood flow in rodent models. This study leveraged the high spatiotemporal resolution of multimodal ultrafast sonography microscopy (MUSM) to assess cerebrovascular hemodynamics in vivo within hypertensive mice induced by Angiotensin II (Ang II) and Nω-nitro-L-arginine methyl ester (L-NAME). Cerebrovascular hemodynamics were quantified using variations in cerebral vascular density, diameter, velocity, tortuosity, cerebral flow pulsatility, and instant flow direction. Our findings revealed a decrease in cerebral vascular density and perfusion index after blood pressure increased, particularly in the cortex and basal ganglia regions. This study not only provides a comprehensive view of cerebral dynamics in hypertension but also introduces MUSM as a novel tool for in vivo cerebrovascular hemodynamic analysis in preclinical animal research.
高血压是脑出血的主要原因。传统的活体脑血管成像技术,如正电子发射断层扫描和磁共振成像,虽然广泛用于脑出血的临床前研究,但在动态显示啮齿动物模型的大脑微循环血流方面往往存在不足。本研究利用多模态超快超声显微镜(MUSM)的高时空分辨率,评估血管紧张素II (Ang II)和ω-硝基- l -精氨酸甲酯(L-NAME)诱导的高血压小鼠体内脑血管血流动力学。通过脑血管密度、直径、速度、扭曲度、脑血流脉动度和瞬时血流方向的变化来量化脑血管血流动力学。我们的研究结果显示,血压升高后脑血管密度和灌注指数下降,特别是在皮层和基底节区。该研究不仅提供了高血压脑动力学的全面视图,而且还介绍了MUSM作为临床前动物研究中体内脑血管血流动力学分析的新工具。
{"title":"Multi-modal Ultrafast Sonography Microscopy (MUSM) for super-resolution imaging of cerebral vascular dynamics in a mouse model of hypertension induced by Angiotensin-II and L-NAME","authors":"Bing-Qiao Wang , Yu-Fan Ma , Guo-Qing Zhang , Ke Yan , Yan-Yun Wang , Qin Zhang , Lan Chen , Chen-Hao Zhao , Sen Lin , Qing-Wu Yang","doi":"10.1016/j.hest.2024.11.001","DOIUrl":"10.1016/j.hest.2024.11.001","url":null,"abstract":"<div><div>Hypertension is a major cause of cerebral hemorrhage. Although they are widely used in preclinical studies on cerebral hemorrhage, traditional in vivo cerebrovascular imaging techniques, such as positron emission tomography and magnetic resonance imaging, often fall short in dynamically visualizing cerebral microcirculation blood flow in rodent models. This study leveraged the high spatiotemporal resolution of multimodal ultrafast sonography microscopy (MUSM) to assess cerebrovascular hemodynamics in vivo within hypertensive mice induced by Angiotensin II (Ang II) and Nω-nitro-L-arginine methyl ester (L-NAME). Cerebrovascular hemodynamics were quantified using variations in cerebral vascular density, diameter, velocity, tortuosity, cerebral flow pulsatility, and instant flow direction. Our findings revealed a decrease in cerebral vascular density and perfusion index after blood pressure increased, particularly in the cortex and basal ganglia regions. This study not only provides a comprehensive view of cerebral dynamics in hypertension but also introduces MUSM as a novel tool for in vivo cerebrovascular hemodynamic analysis in preclinical animal research.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 4","pages":"Pages 154-161"},"PeriodicalIF":1.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2024-10-10DOI: 10.1016/j.hest.2024.10.001
Shijie Mao , Shi Tang , Qi Wang , Ling Shen , Ying Bai
Intracerebral hemorrhage (ICH), which is a form of stroke triggered by the rupture of blood vessels within the brain tissue, is a leading cause of morbidity and mortality worldwide. Although significant progress has been made in comprehending the pathophysiology, diagnosis, and treatment of ICH, effective therapies remain limited, and specific biomarkers for monitoring disease progression are still lacking. Non-coding RNAs (ncRNAs) have been shown to be promising biomarkers in numerous central nervous system (CNS) diseases. In particular, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are usually studied as potential targets for disease therapy. However, their roles in ICH are not yet fully understood. This review seeks to consolidate current knowledge on the roles of ncRNAs in ICH, explore the underlying mechanisms, and discuss potential therapeutic strategies.
{"title":"Non-coding RNAs in intracerebral hemorrhage: Roles, mechanisms, and therapeutic implications","authors":"Shijie Mao , Shi Tang , Qi Wang , Ling Shen , Ying Bai","doi":"10.1016/j.hest.2024.10.001","DOIUrl":"10.1016/j.hest.2024.10.001","url":null,"abstract":"<div><div>Intracerebral hemorrhage (ICH), which is a form of stroke triggered by the rupture of blood vessels within the brain tissue, is a leading cause of morbidity and mortality worldwide. Although significant progress has been made in comprehending the pathophysiology, diagnosis, and treatment of ICH, effective therapies remain limited, and specific biomarkers for monitoring disease progression are still lacking. Non-coding RNAs (ncRNAs) have been shown to be promising biomarkers in numerous central nervous system (CNS) diseases. In particular, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are usually studied as potential targets for disease therapy. However, their roles in ICH are not yet fully understood. This review seeks to consolidate current knowledge on the roles of ncRNAs in ICH, explore the underlying mechanisms, and discuss potential therapeutic strategies.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 4","pages":"Pages 188-194"},"PeriodicalIF":1.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-03-02DOI: 10.1016/j.hest.2025.02.002
Wenying Zhang , Wanyu Ma , Siying Ren , Likun Wang , Guofeng Wu
Intracerebral hemorrhage (ICH) is a severe stroke subtype with high mortality and disability. Cuproptosis is a regulatory cell death modality dependent on intracellular copper ion concentration, the role of which in ICH is unclear. Upon activation by ligand agonists, peroxisome proliferator-activated receptor-γ (PPARγ), can alleviate brain injury after ICH. To investigate the inhibitory effect of activating PPARγ on cuproptosis following ICH, we established the ICH model in vivo and in vitro and they were treated with the PPARγ agonist or antagonist after models being established successfully. Then, the copper ion concentration was measured by copper colorimetric assay and the expression of cuproptosis-related regulatory factors and copper transporter 1 was detected by western blotting and immunofluorescence staining (except in the cell level). We found that the increase in copper ion concentration following ICH leads to the disruption of copper homeostasis, inducing cuproptosis via copper toxicity. Activating PPARγ regulates the expression of cuproptosis-associated positive or negative regulatory factors and mitigates copper toxicity by inhibiting the influx of copper ions into the cell, thereby inhibiting cuproptosis. This study not only reveals the relationship between ICH and cuproptosis but also may provide new therapeutic strategies for improving the prognosis of patients with ICH.
{"title":"A pretest on cuproptosis: Activating PPARγ inhibits cuproptosis following intracerebral hemorrhage","authors":"Wenying Zhang , Wanyu Ma , Siying Ren , Likun Wang , Guofeng Wu","doi":"10.1016/j.hest.2025.02.002","DOIUrl":"10.1016/j.hest.2025.02.002","url":null,"abstract":"<div><div>Intracerebral hemorrhage (ICH) is a severe stroke subtype with high mortality and disability. Cuproptosis is a regulatory cell death modality dependent on intracellular copper ion concentration, the role of which in ICH is unclear. Upon activation by ligand agonists, peroxisome proliferator-activated receptor-γ (PPARγ), can alleviate brain injury after ICH. To investigate the inhibitory effect of activating PPARγ on cuproptosis following ICH, we established the ICH model in vivo and in vitro and they were treated with the PPARγ agonist or antagonist after models being established successfully. Then, the copper ion concentration was measured by copper colorimetric assay and the expression of cuproptosis-related regulatory factors and copper transporter 1 was detected by western blotting and immunofluorescence staining (except in the cell level). We found that the increase in copper ion concentration following ICH leads to the disruption of copper homeostasis, inducing cuproptosis via copper toxicity. Activating PPARγ regulates the expression of cuproptosis-associated positive or negative regulatory factors and mitigates copper toxicity by inhibiting the influx of copper ions into the cell, thereby inhibiting cuproptosis. This study not only reveals the relationship between ICH and cuproptosis but also may provide new therapeutic strategies for improving the prognosis of patients with ICH.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 4","pages":"Pages 166-175"},"PeriodicalIF":1.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2024-11-01DOI: 10.1016/j.hest.2024.10.005
Sihui Wang , Xiaochen Wang , Xuening Zhao , Lingxu Chen , Shengjun Sun
Objective
Intracerebral hemorrhage (ICH) is a highly fatal and incapacitating form of stroke. Perihematomal edema (PHE) serves as a measurable radiological indicator in the progression of secondary injury and holds significant relevance in the assessment of disease outcome. Through a longitudinal cohort study, we examined the association between the expansion of peak PHE and functional outcome.
Methods
We retrospectively enrolled supratentorial ICH patients with available computed tomography (CT) scans on admission within 6 h as well as day 1, day 8 ± 2, day 12 ± 2. Peak PHE expansion was defined as the the difference between maximum volume measured in any of the available CT scans and PHE volume on admission. We stratified patients into groups with unfavorable and favorable outcome, utilizing the modified Rankin Scale (mRS) score at the 90-day mark post-onset (with an mRS score >3 signifying an unfavorable outcome)
Results
Eventually, a total of 140 patients were enrolled, and 84 patients (60 %) had poor outcome on day 90. Multivariable logistic regression revealed peak PHE expansion (OR 1.098 [95 % CI 1.049–1.150]) was independently associated with poor outcome. The best cutoff value was 12.8 ml with an AUC of 0.842.
Conclusion
The peak PHE expansion correlates independently with adverse outcome for ICH patients within three months post-injury. It is anticipated that interventional therapies administered during the edema expansion phase could enhance the prognosis for ICH patients.
目的脑出血是一种致死率高、致残性强的脑卒中形式。血肿周围水肿(PHE)是继发性损伤进展中可测量的影像学指标,在疾病结局评估中具有重要意义。通过一项纵向队列研究,我们研究了PHE峰值扩大与功能结局之间的关系。方法回顾性研究幕上脑出血患者入院后6小时、第1天、第8天±2天、第12天±2天的CT扫描。PHE扩张峰值定义为在任何可用的CT扫描中测量到的最大体积与入院时PHE体积之间的差异。我们在发病后90天采用改良的Rankin量表(mRS)评分将患者分为预后不良组和预后良好组(mRS评分为bb0.3表示预后不良)。结果最终,共纳入140例患者,其中84例(60%)患者在第90天预后不良。多变量logistic回归显示PHE扩张峰值(OR 1.098 [95% CI 1.049-1.150])与预后不良独立相关。最佳临界值为12.8 ml, AUC为0.842。结论脑出血患者损伤后3个月内PHE扩张高峰与不良预后独立相关。预计在水肿扩张期进行介入治疗可以改善脑出血患者的预后。
{"title":"Peak perihematomal edema expansion predicts poor outcome in patients with intracerebral hemorrhage","authors":"Sihui Wang , Xiaochen Wang , Xuening Zhao , Lingxu Chen , Shengjun Sun","doi":"10.1016/j.hest.2024.10.005","DOIUrl":"10.1016/j.hest.2024.10.005","url":null,"abstract":"<div><h3>Objective</h3><div>Intracerebral hemorrhage (ICH) is a highly fatal and incapacitating form of stroke. Perihematomal edema (PHE) serves as a measurable radiological indicator in the progression of secondary injury and holds significant relevance in the assessment of disease outcome. Through a longitudinal cohort study, we examined the association between the expansion of peak PHE and functional outcome.</div></div><div><h3>Methods</h3><div>We retrospectively enrolled supratentorial ICH patients with available computed tomography (CT) scans on admission within 6 h as well as day 1, day 8 ± 2, day 12 ± 2. Peak PHE expansion was defined as the the difference between maximum volume measured in any of the available CT scans and PHE volume on admission. We stratified patients into groups with unfavorable and favorable outcome, utilizing the modified Rankin Scale (mRS) score at the 90-day mark post-onset (with an mRS score >3 signifying an unfavorable outcome)</div></div><div><h3>Results</h3><div>Eventually, a total of 140 patients were enrolled, and 84 patients (60 %) had poor outcome on day 90. Multivariable logistic regression revealed peak PHE expansion (OR 1.098 [95 % CI 1.049–1.150]) was independently associated with poor outcome. The best cutoff value was 12.8 ml with an AUC of 0.842.</div></div><div><h3>Conclusion</h3><div>The peak PHE expansion correlates independently with adverse outcome for ICH patients within three months post-injury. It is anticipated that interventional therapies administered during the edema expansion phase could enhance the prognosis for ICH patients.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 4","pages":"Pages 148-153"},"PeriodicalIF":1.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: With the aging population, the number of elderly patients with severe traumatic brain injury (sTBI) inevitably increases. The high mortality rate for sTBI in the elderly necessitates effective solutions. While we have previously reported the beneficial effects of a novel barbiturate therapy, a prophylactic step-down infusion of barbiturates (sdB), using thiamylal with normothermia (NOR) in patients with sTBI, its effects on elderly patients remain unclear. This study aimed to compare the efficacy and safety of sdB between elderly and non-elderly patients with sTBI.
Methods: We included 25 sTBI patients treated with sdB+NOR between January 2013 and March 2020. Patients were stratified into elderly (≥75 years, n = 8) and non-elderly (<75 years, n = 17) groups. Patient characteristics were similar between groups except for sex ratio. Outcomes compared included primary endpoints (favorable outcome at discharge and at 6–12 months), secondary endpoints (composite death at discharge and at 6–12 months), side effects, complications, intracranial pressure (ICP), cerebral perfusion pressure (CPP) control, and hospitalization period.
Results: The hospitalization period tended to be longer in elderly patients. There were no significant differences in the incidence of side effects or complications related to sdB between the groups. Both primary (favorable outcome) and secondary (composite death) endpoints were similar at discharge and at 6-12 months for elderly and non-elderly patients. ICP and CPP were well controlled in the elderly patients.
Conclusion: The results suggest that sdB+NOR is as effective and safe for elderly patients with sTBI as it is for non-elderly patients.
{"title":"Prophylactic barbiturate step-down infusion therapy has similar and favorable effects in elderly and non-elderly patients with severe traumatic brain injuries","authors":"Sosho Kajiwara , Yu Hasegawa , Jin Kikuchi , Kiyohiko Sakata , Tetsuya Negoto , Yukihiko Nakamura , Takayuki Kawano , Yusuke Otsu , Yoshikuni Kotaki , Hideo Nakamura , Masaru Hirohata , Motohiro Morioka","doi":"10.1016/j.hest.2024.10.002","DOIUrl":"10.1016/j.hest.2024.10.002","url":null,"abstract":"<div><div><em>Objective</em>: With the aging population, the number of elderly patients with severe traumatic brain injury (sTBI) inevitably increases. The high mortality rate for sTBI in the elderly necessitates effective solutions. While we have previously reported the beneficial effects of a novel barbiturate therapy, a prophylactic step-down infusion of barbiturates (sdB), using thiamylal with normothermia (NOR) in patients with sTBI, its effects on elderly patients remain unclear. This study aimed to compare the efficacy and safety of sdB between elderly and non-elderly patients with sTBI.</div><div><em>Methods</em>: We included 25 sTBI patients treated with sdB+NOR between January 2013 and March 2020. Patients were stratified into elderly (≥75 years, n = 8) and non-elderly (<75 years, n = 17) groups. Patient characteristics were similar between groups except for sex ratio. Outcomes compared included primary endpoints (favorable outcome at discharge and at 6–12 months), secondary endpoints (composite death at discharge and at 6–12 months), side effects, complications, intracranial pressure (ICP), cerebral perfusion pressure (CPP) control, and hospitalization period.</div><div><em>Results</em>: The hospitalization period tended to be longer in elderly patients. There were no significant differences in the incidence of side effects or complications related to sdB between the groups. Both primary (favorable outcome) and secondary (composite death) endpoints were similar at discharge and at 6-12 months for elderly and non-elderly patients. ICP and CPP were well controlled in the elderly patients.</div><div><em>Conclusion</em>: The results suggest that sdB+NOR is as effective and safe for elderly patients with sTBI as it is for non-elderly patients.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 4","pages":"Pages 143-147"},"PeriodicalIF":1.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-02-17DOI: 10.1016/j.hest.2024.12.001
Zhixin Li , Riguge Su , Yu Zhang , Duanlu Hou , Basak Caner , Wei Yan , Xiaobo Yang , Heling Chu , Yuping Tang
<div><h3>Objective</h3><div>Hemorrhagic transformation (HT) of cerebral infarction is considered as one of the most serious complications. Increasing evidence show that statin use might reduce the neuroinflammation and even improve clinical prognosis of stroke patients. However, there is not enough evidence that premorbid statin use may affect the risk of hemorrhagic transformation in stroke patients. The aim of our study was to investigate the role of premorbid long-term statin use in HT after acute ischemic stroke.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed ischemic stroke patients in Huashan Hospital from 1 January 2012 to 31 December 2022 based on hospital electronic case records. Since thrombolysis or thrombectomy might interfere with the effect of statin use we excluded patients who received thrombolysis or thrombectomy treatment. A matched case-control study was conducted for reducing the impact of various confounding factors. The independent roles of statin use and serum lipids in HT was evaluated by binary logistic regression analysis.</div></div><div><h3>Results</h3><div>A total of 254 ischemic stroke patients met the inclusion criteria and have been matched at 1:1 ratio, according age (± 5 years), admission NIHSS (± 3 scores), prior antiplatelets and anticoagulation therapy and previous stroke history. The patients without HT were regarded as control group. The percentage of HT was significantly lower in patients with premorbid long-term statin use (22.1 % vs. 41.7 %, p = 0.001). The incidence rate of diabetes mellitus and symptomatic deterioration (NIHSS increase ≥ 4) was higher in patients with HT. There were 18 patients having intracerebral hemorrhage before any reperfusion treatment. They had lower level of LDL-C (1.76 (1.73, 2.26) vs 2.72 (2.28, 3.09), p < 0.001) and were prone to previously take statins (55.6 % vs 16.5 %,p < 0.001). However, ECASS classification and all the outcome scores did not present any statistical difference in our study. In logistic regression analysis DM (OR = 2.001, 95 %CI 1.124–3.563, <em>p</em> = 0.018), increased levels of LDC-C (OR = 0.334, 95 %CI 0.172–0.649), <em>p</em> = 0.001) and HDL-C (OR = 13.303, 95 %CI 2.050–86.328, p = 0.001) were independent risk factors in occurrence of HT in patients with ischemic stroke, while premorbid statin use (OR = 0.269, 95 %CI 0.117–0.615, p = 0.002) could still be regarded as a protective factor in preventing intracranial hemorrhage after cerebral infarction. Additionally, lower level of LDL-C was also an independent risk factor in spontaneous HT after cerebral infarction (OR = 45.45, 95 %CI 5.62–333.33, p < 0.001), regardless of statin use.</div></div><div><h3>Conclusion</h3><div>Premorbid long-term statin use plays a protective role in the HT after cerebral infarction. However, low serum LDL-C and high HDL-C might be independent risk factors in the occurrence of HT irrespective of statin use. The previous statin uses and serum li
目的脑梗死的出血性转化(HT)被认为是最严重的并发症之一。越来越多的证据表明,他汀类药物的使用可能减少神经炎症,甚至改善脑卒中患者的临床预后。然而,没有足够的证据表明发病前使用他汀类药物可能会影响中风患者出血转化的风险。本研究的目的是探讨发病前长期使用他汀类药物在急性缺血性卒中后HT中的作用。方法回顾性分析华山医院2012年1月1日至2022年12月31日缺血性脑卒中患者的电子病历。由于溶栓或取栓可能会干扰他汀类药物使用的效果,我们排除了接受溶栓或取栓治疗的患者。为了减少各种混杂因素的影响,进行了匹配的病例对照研究。通过二元logistic回归分析评估他汀类药物使用和血脂在HT中的独立作用。结果254例缺血性脑卒中患者符合纳入标准,按年龄(±5岁)、入院NIHSS(±3分)、既往抗血小板和抗凝治疗及既往脑卒中史按1:1比例进行匹配。没有HT的患者作为对照组。在发病前长期使用他汀类药物的患者中,HT的比例显著降低(22.1%对41.7%,p = 0.001)。HT患者糖尿病及症状恶化发生率(NIHSS升高≥4)较高。再灌注治疗前有脑出血18例。他们的LDL-C水平较低(1.76 (1.73,2.26)vs 2.72 (2.28, 3.09), p <;0.001),既往倾向于服用他汀类药物(55.6% vs 16.5%,p <;0.001)。然而,在我们的研究中,ECASS分类和所有结局评分没有统计学差异。在logistic回归分析中,DM (OR = 2.001, 95% CI 1.124 ~ 3.563, p = 0.018)、LDC-C升高(OR = 0.334, 95% CI 0.172 ~ 0.649)、HDL-C升高(OR = 13.303, 95% CI 2.050 ~ 86.328, p = 0.001)是缺血性脑卒中患者发生HT的独立危险因素,而发病前使用他汀类药物(OR = 0.269, 95% CI 0.117 ~ 0.615, p = 0.002)仍可视为预防脑梗死后颅内出血的保护因素。此外,低LDL-C水平也是脑梗死后自发性HT的独立危险因素(OR = 45.45, 95% CI 5.62-333.33, p <;0.001),与他汀类药物的使用无关。结论发病前长期使用他汀类药物对脑梗死后HT有保护作用。然而,血清低LDL-C和高HDL-C可能是发生HT的独立危险因素,与他汀类药物的使用无关。既往他汀类药物的使用和血脂水平对HT的预后没有影响。
{"title":"Premorbid long-term statin use can reduce the risk of hemorrhagic transformation after ischemic stroke","authors":"Zhixin Li , Riguge Su , Yu Zhang , Duanlu Hou , Basak Caner , Wei Yan , Xiaobo Yang , Heling Chu , Yuping Tang","doi":"10.1016/j.hest.2024.12.001","DOIUrl":"10.1016/j.hest.2024.12.001","url":null,"abstract":"<div><h3>Objective</h3><div>Hemorrhagic transformation (HT) of cerebral infarction is considered as one of the most serious complications. Increasing evidence show that statin use might reduce the neuroinflammation and even improve clinical prognosis of stroke patients. However, there is not enough evidence that premorbid statin use may affect the risk of hemorrhagic transformation in stroke patients. The aim of our study was to investigate the role of premorbid long-term statin use in HT after acute ischemic stroke.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed ischemic stroke patients in Huashan Hospital from 1 January 2012 to 31 December 2022 based on hospital electronic case records. Since thrombolysis or thrombectomy might interfere with the effect of statin use we excluded patients who received thrombolysis or thrombectomy treatment. A matched case-control study was conducted for reducing the impact of various confounding factors. The independent roles of statin use and serum lipids in HT was evaluated by binary logistic regression analysis.</div></div><div><h3>Results</h3><div>A total of 254 ischemic stroke patients met the inclusion criteria and have been matched at 1:1 ratio, according age (± 5 years), admission NIHSS (± 3 scores), prior antiplatelets and anticoagulation therapy and previous stroke history. The patients without HT were regarded as control group. The percentage of HT was significantly lower in patients with premorbid long-term statin use (22.1 % vs. 41.7 %, p = 0.001). The incidence rate of diabetes mellitus and symptomatic deterioration (NIHSS increase ≥ 4) was higher in patients with HT. There were 18 patients having intracerebral hemorrhage before any reperfusion treatment. They had lower level of LDL-C (1.76 (1.73, 2.26) vs 2.72 (2.28, 3.09), p < 0.001) and were prone to previously take statins (55.6 % vs 16.5 %,p < 0.001). However, ECASS classification and all the outcome scores did not present any statistical difference in our study. In logistic regression analysis DM (OR = 2.001, 95 %CI 1.124–3.563, <em>p</em> = 0.018), increased levels of LDC-C (OR = 0.334, 95 %CI 0.172–0.649), <em>p</em> = 0.001) and HDL-C (OR = 13.303, 95 %CI 2.050–86.328, p = 0.001) were independent risk factors in occurrence of HT in patients with ischemic stroke, while premorbid statin use (OR = 0.269, 95 %CI 0.117–0.615, p = 0.002) could still be regarded as a protective factor in preventing intracranial hemorrhage after cerebral infarction. Additionally, lower level of LDL-C was also an independent risk factor in spontaneous HT after cerebral infarction (OR = 45.45, 95 %CI 5.62–333.33, p < 0.001), regardless of statin use.</div></div><div><h3>Conclusion</h3><div>Premorbid long-term statin use plays a protective role in the HT after cerebral infarction. However, low serum LDL-C and high HDL-C might be independent risk factors in the occurrence of HT irrespective of statin use. The previous statin uses and serum li","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 3","pages":"Pages 95-102"},"PeriodicalIF":1.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-02-18DOI: 10.1016/j.hest.2025.01.003
Qiaoqiao Xu, Wei Mei
Brain injury is one of the leading causes of death and disability worldwide, attributable to diverse etiologies such as trauma, hypoxia, stroke, infection, or neurodegenerative diseases. Due to the complex pathophysiology, high prevalence, and limited therapeutic options, brain injury poses significant healthcare challenges. Current treatment for brain injury involves a combination of medical interventions, surgery, and rehabilitation therapies. Ligustilide, a bioactive component purified from traditional Chinese medicinal herb, has been studied as a promising candidate for neuroprotection. In this review, we summarize current research to understand the mechanisms underlying ligustilide neuroprotective activities and assess its therapeutic potential in treating brain injuries.
{"title":"Advancing brain injury treatment and neuroprotection with ligustilide: Mechanisms and therapeutic potential","authors":"Qiaoqiao Xu, Wei Mei","doi":"10.1016/j.hest.2025.01.003","DOIUrl":"10.1016/j.hest.2025.01.003","url":null,"abstract":"<div><div>Brain injury is one of the leading causes of death and disability worldwide, attributable to diverse etiologies such as trauma, hypoxia, stroke, infection, or neurodegenerative diseases. Due to the complex pathophysiology, high prevalence, and limited therapeutic options, brain injury poses significant healthcare challenges. Current treatment for brain injury involves a combination of medical interventions, surgery, and rehabilitation therapies. Ligustilide, a bioactive component purified from traditional Chinese medicinal herb, has been studied as a promising candidate for neuroprotection. In this review, we summarize current research to understand the mechanisms underlying ligustilide neuroprotective activities and assess its therapeutic potential in treating brain injuries.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 3","pages":"Pages 121-127"},"PeriodicalIF":1.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruptured basilar artery perforator aneurysm (BAPA) is a rare cause of subarachnoid hemorrhage (SAH) and is difficult to diagnose.
Case presentation
A 60-year-old male was rushed to our hospital due to severe headache. Computed tomography (CT) showed diffuse SAH, and 3-dimensional CT angiography (CTA) showed a saccular aneurysm in the left anterior cerebral artery (ACA), which was treated with clipping. However, intraoperative findings showed little SAH around the aneurysm and neither a rupture point nor a white thrombus on the aneurysm. Postoperative CT showed a marked decrease in SAH in the prepontine cistern, and digital subtraction angiography (DSA) showed disappearance of the ACA aneurysm and no other lesions. SAH in the prepontine cistern re-increased on CT on the 6th postoperative day, when CTA failed to show the cause. On the 12th postoperative day, CT showed further increased SAH in the prepontine cistern, and DSA revealed a BAPA. Stent-assisted coil embolization was planned at the chronic phase, but the patient went into cardiac arrest the next day, presumably due to a third re-rupture of the BAPA.
Conclusion
The coexistence of a ruptured BAPA and an unruptured saccular aneurysm is extremely challenging in terms of both diagnosis and treatment strategy.
{"title":"Coexistence of ruptured basilar artery perforator aneurysm undetected on initial angiogram and unruptured anterior cerebral artery saccular aneurysm: Case report and literature review","authors":"Hideki Nakajima , Yu Sato , Tetsushi Yago , Kazuhiko Tsuda , Hidenori Suzuki","doi":"10.1016/j.hest.2024.07.008","DOIUrl":"10.1016/j.hest.2024.07.008","url":null,"abstract":"<div><h3>Objective</h3><div>Ruptured basilar artery perforator aneurysm (BAPA) is a rare cause of subarachnoid hemorrhage (SAH) and is difficult to diagnose.</div></div><div><h3>Case presentation</h3><div>A 60-year-old male was rushed to our hospital due to severe headache. Computed tomography (CT) showed diffuse SAH, and 3-dimensional CT angiography (CTA) showed a saccular aneurysm in the left anterior cerebral artery (ACA), which was treated with clipping. However, intraoperative findings showed little SAH around the aneurysm and neither a rupture point nor a white thrombus on the aneurysm. Postoperative CT showed a marked decrease in SAH in the prepontine cistern, and digital subtraction angiography (DSA) showed disappearance of the ACA aneurysm and no other lesions. SAH in the prepontine cistern re-increased on CT on the 6th postoperative day, when CTA failed to show the cause. On the 12th postoperative day, CT showed further increased SAH in the prepontine cistern, and DSA revealed a BAPA. Stent-assisted coil embolization was planned at the chronic phase, but the patient went into cardiac arrest the next day, presumably due to a third re-rupture of the BAPA.</div></div><div><h3>Conclusion</h3><div>The coexistence of a ruptured BAPA and an unruptured saccular aneurysm is extremely challenging in terms of both diagnosis and treatment strategy.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 3","pages":"Pages 138-141"},"PeriodicalIF":1.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141853799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2024-09-07DOI: 10.1016/j.hest.2024.09.001
Yi Luo , Maokun Li
Aneurysmal subarachnoid hemorrhage affects 6 to 9 out of every 100,000 people annually, with a mortality rate of 35%. Many people suffer from long-term disabilities, often associated with cognitive impairment. Aneurysmal subarachnoid hemorrhage requires timely stabilization, diagnosis, and treatment. The typical manifestation of severe headaches is common. There are also a wide range of symptoms, including mild pain and coma. We delve into the importance of the field, the significance of ongoing research, and the advancements made in diagnosing and treating this condition, aiming to provide a comprehensive overview.
{"title":"The Progressive Frontier of Aneurysmal subarachnoid Hemorrhage: Diagnosis and treatment Advances","authors":"Yi Luo , Maokun Li","doi":"10.1016/j.hest.2024.09.001","DOIUrl":"10.1016/j.hest.2024.09.001","url":null,"abstract":"<div><div>Aneurysmal subarachnoid hemorrhage affects 6 to 9 out of every 100,000 people annually, with a mortality rate of 35%. Many people suffer from long-term disabilities, often associated with cognitive impairment. Aneurysmal subarachnoid hemorrhage requires timely stabilization, diagnosis, and treatment. The typical manifestation of severe headaches is common. There are also a wide range of symptoms, including mild pain and coma. We delve into the importance of the field, the significance of ongoing research, and the advancements made in diagnosing and treating this condition, aiming to provide a comprehensive overview.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 3","pages":"Pages 128-137"},"PeriodicalIF":1.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}