Translational Stroke Research最新文献

{"title":"Gamma-Benzylidene Digoxin Derivative Attenuates Neurotoxicity Response in a Murine Stroke Model.","authors":"Bruno de Souza Gonçalves, Carla P Dos Santos, Matheus V Machado, Marina M Toledo, Hélio B Dos Santos, Ralph G Thomé, Grazielle A S Maia, Cristiane Q Tilelli, Luciana E D de Carvalho, Hérica L Santos, Vanessa F Cortes, Maira C Lima, Leandro A Barbosa, José A F P Villar","doi":"10.1007/s12975-025-01365-x","DOIUrl":"https://doi.org/10.1007/s12975-025-01365-x","url":null,"abstract":"<p><p>Stroke is a prevalent age-related disease globally, contributing significantly to neurological dysfunction, disability, and mortality rates. Despite its substantial healthcare burden, effective therapies remain limited. Na/K-ATPase (NKA), beyond its canonical role in ion homeostasis, emerges as a pivotal player in oxidative stress induction, implicating its potential as a therapeutic target. Here, we investigate the efficacy of the semi-synthetic cardiotonic steroid gamma-benzylidene digoxin-15 (BD-15) in ameliorating brain ischemia-induced damage. A total of 44 male Wistar albino rats were randomly assigned to four groups (n = 11/group). The animals were subjected to experimental brain ischemia induction and treated with BD-15. Behavioral assessments revealed a significant improvement in mobility and exploration in BD-15-treated rats compared to brain ischemia alone (P < 0.05). Histological analysis suggested a reduction in brain damage in BD-15-treated rats. Moreover, BD-15 administration attenuated oxidative stress, evidenced by decreased thiobarbituric acid reactive substances levels (TBARS) in the hippocampus and sensory-motor cortex in brain ischemia rats (P < 0.05). Additionally, BD-15 treatment mitigated changes in lipid composition, possibly via modulation of membrane integrity. BD-15 also significantly restored ionic homeostasis in brain ischemia rats, improving the activities of NKA, Ca²⁺-ATPase, Sarcoendoplasmic Reticulum Calcium ATPase, and Mg²⁺-ATPase activities in the hippocampus and sensory-motor cortex (P < 0.05). Notably, acetylcholinesterase activity in brain ischemia rats was improved after BD-15 treatment (P < 0.05), suggesting additional benefits in maintaining neurotransmission following ischemic injury. These findings suggest a multifaceted neuroprotective mechanism of BD-15 in brain ischemia pathology. Our results propose BD-15 as a promising therapeutic strategy for mitigating ischemia-induced neurotoxicity. Further clinical studies are necessary to validate these findings and explore the translational potential of BD-15 in human stroke management.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Hypoxia-Induced Neuroprotection Mechanisms in Post-Stroke Recovery.","authors":"Malachi Nyamukondiwa, Elizaveta S Koneva, Eugeny E Achkasov, Zhang Xinliang, Padmanabha Reddy Y, Narasimha M Beeraka, Oleg S Glazachev","doi":"10.1007/s12975-025-01364-y","DOIUrl":"https://doi.org/10.1007/s12975-025-01364-y","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Stroke recovery is a multifaceted process influenced by various neuroprotective mechanisms that support long-term rehabilitation. Recent studies on hypoxia-induced neuroprotection have shown promising potential in enhancing stroke recovery through adaptive cellular responses. Hypoxic conditioning in techniques of passive intermittent hypoxic exposures (IHE) or intermittent hypoxic-hyperoxic exposures (IHHE), which alternates between low and normal/high oxygen levels, is emerging as a novel complementary therapy that may improve post-stroke outcomes by promoting neuroprotection, neurogenesis, and vascular remodeling. This review aims to explore the therapeutic implications of IHE/IHHE as a novel complementary therapy to mitigate post-stroke exacerbations and enhance recovery through various physiological and molecular mechanisms. A comprehensive literature search was conducted using public databases such as PubMed, Scopus, Relemed, the National Library of Medicine, and Google Scholar. The search focused on studies related to hypoxia training, neuroprotection, stroke recovery, and IHE/IHHE. The review synthesizes current findings on the pathophysiological insights and therapeutic potential of intermittent hypoxic conditioning in stroke rehabilitation. The review highlights several key areas where IHE/IHHE shows adaptive responses involving hypoxia-inducible factor (HIF) signaling, reactive oxygen species (ROS) regulation, and mitochondrial energetics, contributing to enhanced neuroprotection and tissue recovery. Angiogenesis and vascular remodeling: IHE/IHHE promotes angiogenesis and improves cerebral blood flow, facilitating vascular remodeling and improved perfusion in damaged brain areas. Neurogenesis: IHE/IHHE enhances neurogenesis, aiding in brain repair and functional recovery by promoting neuronal survival and regeneration. Cognitive and motor function: IHE/IHHE has been shown to improve cognitive performance and motor function in post-stroke patients, as well as in elderly individuals with mild cognitive impairment. Cardioprotection: IHE/IHHE reduces cardiovascular risk factors, such as hypertension and inflammation, and has been shown to enhance cardiac function in patients with ischemic heart disease. Integrative rehabilitation: Incorporating IHE/IHHE into post-stroke rehabilitation programs may enhance physical and cognitive outcomes, supporting a holistic approach to recovery. Hypoxic conditioning in modes of IHE/IHHE represents a promising complementary therapy for stroke recovery, leveraging adaptive responses to hypoxia and hyperoxia to promote neuroprotection, neurogenesis, and vascular remodeling. Further research is needed to optimize IHHE protocols, understand their long-term effects, and integrate them effectively into clinical practice. This review benefits physicians, molecular biologists, and neurologists and describes the potential of IHE/IHHE in enhancing stroke rehabilitation outcomes, and highlights the need for wel","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565325","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 of NETs Markers with Clinical and Radiological Outcomes in Patients with Acute Ischemic Stroke Undergoing Thrombectomy: Does Heparin Treatment Modify This?","authors":"Aarazo Barakzie, Wouter van der Steen, A J Gerard Jansen, Bob Roozenbeek, Samantha J Donkel, Aad van der Lugt, Hester Lingsma, Diederik W J Dippel, Hugo Ten Cate, Moniek P M de Maat","doi":"10.1007/s12975-025-01362-0","DOIUrl":"https://doi.org/10.1007/s12975-025-01362-0","url":null,"abstract":"<p><p>The aim of this study is to investigate the association of neutrophil extracellular traps (NETs) markers with clinical and radiological outcomes in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT) and assess the effect of periprocedural heparin during EVT on NETs markers and their association with outcomes. From 198 AIS patients included in the MRCLEAN-MED trial, randomized to receive EVT with (N = 104) or without (N = 94) low-dose unfractionated heparin (5000 IU bolus followed by 500 IU/h for 6 h, n = 104), blood samples were collected at baseline, 1 h, and 24 h post-reperfusion. NETs markers (MPO-DNA, histone-DNA, citrullinated histone H3 [CitH3]) were measured in blood samples, and their associations with stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at 24 h post-reperfusion), long-term functional outcome (modified Rankin Scale [mRS] score at 90-day), and final infarct size (5-7 days) were assessed in EVT and heparin + EVT-treated patients using logistic regression, linear regression, and Pearson's correlation. Histone-DNA levels at 1 h post-heparin + EVT, but not EVT alone, were positively associated with final infarct size. Histone-DNA levels at 24 h post-heparin + EVT were negatively associated with infarct size mRS and NIHSS, while baseline CitH3 was positively correlated with NIHSS at 24 h post-EVT. Interaction analysis showed that the association between histone-DNA levels at 24 h and NIHSS at 24 h was different in the two treatment groups. No further associations were observed. At 1 h post-heparin + EVT, the histone-DNA levels were independently associated with larger infarct size, while at 24 h, histone-DNA linked to improved outcomes post-heparin + EVT and baseline-CitH3 to worse outcomes post-EVT, suggesting heparin may attenuate histone-DNA's effect on outcome.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508392","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":"Gut Microbiota Improve the Prediction of Stroke-Associated Pneumonia Risk and Outcomes in Acute Ischemic Stroke.","authors":"Yi-Si Lin, Jia-Hao Chen, Wei-Hao Zhuang, Jia-Ni Huang, Yi-Han Chen, Jie Zhang, Jia Li, Meng Huang, Jia-Long Hou, Shuang-Jie Qian, Zhi-Bo Chen, Yan-Lei Zhang, Ruo-Ting Xu","doi":"10.1007/s12975-025-01363-z","DOIUrl":"https://doi.org/10.1007/s12975-025-01363-z","url":null,"abstract":"<p><p>Stroke-associated pneumonia (SAP) is the most significant acute ischemic stroke (AIS) comorbidity. This investigation aimed to explore the relationship between gut microbiome composition and SAP risk in patients with moderate-to-severe AIS and to develop a robust and accessible SAP risk-prediction model for this population. This prospective study included AIS patients with an NIHSS score ≥ 9 within 48 h of onset who were admitted to the First Affiliated Hospital of Wenzhou Medical University. Rectal swabs and sputum samples were collected for 16S rRNA gene sequencing and analyzed via QIIME to evaluate microbial composition. Blood samples were subjected to untargeted metabolomics analysis via liquid chromatography‒mass spectrometry (LC‒MS). Logistic and Cox regression analyses were conducted (α = 0.05). Fifty of 104 AIS patients (48.1%) developed SAP. Microbiota abundances significantly differed between groups. Logistic regression analysis revealed that Finegoldia protected against SAP (OR 0.710, 95% CI: 0.533 - 0.946, p = 0.019), whereas Lactobacillus (OR 1.347, 95% CI: 1.015 - 1.789, p = 0.039) increased SAP risk. An improved SAP prediction model combining the A²DS² score with seven taxa yielded an AUC of 0.746 (95% CI: 0.650 - 0.841, p < 0.001). Cox regression analysis revealed that genus Clostridium (HR 1.618, 95% CI: 1.241 - 2.110, p < 0.001) was an independent risk factor for mortality, whereas genus Streptococcus (HR 0.751, 95% CI: 0.589 - 0.958, p = 0.021) was a protective factor. Our findings suggest that combining clinical indicators, gut microbiota, and blood metabolites enhances SAP prediction. Furthermore, microorganisms can potentially serve as prognostic markers and therapeutic targets for SAP in the future.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275964","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":"SMART-M24: A Prognostic Nomogram for Long-Term Mortality in Acute Ischemic Stroke Beyond 24 H from Symptom Onset.","authors":"Soo-Hyun Park, Ji Sung Lee, Tae Jung Kim, Mi Sun Oh, Ji-Woo Kim, Kyungbok Lee, Kyung-Ho Yu, Byung-Chul Lee, Byung-Woo Yoon, Sang-Bae Ko","doi":"10.1007/s12975-025-01361-1","DOIUrl":"https://doi.org/10.1007/s12975-025-01361-1","url":null,"abstract":"<p><p>Prognostication after acute ischemic stroke is crucial for long-term care plans. Although hyperacute management significantly affects outcomes, prognostic factors for patients receiving delayed care remain unknown. This study aimed to evaluate predictors and develop a method for estimating long-term mortality in patients with delayed hospital arrival 24 h after stroke symptom onset. Between January 2008 and December 2014, ischemic stroke patients who were admitted to the hospital more than 24 h from symptom onset were included in the linked dataset provided by the Clinical Research Center for Stroke, linked with claims data from the Health Insurance Review and Assessment Service. A nomogram was developed to estimate long-term mortality using clinical variables, with a predictive model assessed by Harrell's C-index. A total of 14,298 patients with acute ischemic stroke (66.5 years, mean age; 58.3%, male) were randomly assigned to training (n = 10,009) and validation (n = 4289) groups. Significant predictors of long-term mortality included older age, lower BMI, higher NIHSS score, stroke etiology, comorbidities (diabetes, coronary artery disease, dialysis, cancer), fasting blood sugar, use of antithrombotics/statins, and functional status at discharge. The Stroke Measures Analysis for Prognostic Testing - Mortality24 (SMART-M24) nomogram incorporated 17 predictors and achieved a C-index of 0.80 (95% CI, 0.79-0.81) in both groups. The SMART-M24 nomogram provides a prognostic tool for estimating long-term mortality in ischemic stroke patients with delayed hospital arrival 24 h after symptom onset. This model can assist clinical decision-making and long-term care planning for patients who have not undergone hyperacute treatment.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249712","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":"Clinical Significance of Somatic PIK3CA and MAP3K3 Mutations in Cerebral and Spinal Cavernous Malformations.","authors":"Hiroki Hongo, Satoru Miyawaki, Keisuke Takai, Hideaki Ono, Masahiro Shimizu, Takashi Matsukawa, Shotaro Ogawa, Yu Teranishi, Satoshi Kiyofuji, Kenta Ohara, Daiichiro Ishigami, Yu Sakai, Seiei Torazawa, Yudai Hirano, Daisuke Shimada, Naoto Kunii, Seijiro Shimada, Jun Mitsui, Hiroto Katoh, Daisuke Komura, Hirofumi Nakatomi, Shumpei Ishikawa, Nobuhito Saito","doi":"10.1007/s12975-025-01360-2","DOIUrl":"https://doi.org/10.1007/s12975-025-01360-2","url":null,"abstract":"<p><p>Somatic PIK3CA and MAP3K3 mutations in cerebral and spinal cavernous malformations (CMs) have been identified in recent studies. However, their significance in the clinical presentation and risk of hemorrhage in CMs remains poorly understood. We aimed to analyze the association between these mutations and the clinical characteristics of CMs. Among patients with CMs who underwent surgical resection of lesions between July 2002 and March 2022, those with complete clinical and radiological data at the time of initial surgery were included. Somatic PIK3CA and MAP3K3 mutations were detected using droplet digital polymerase chain reaction. Subsequently, the clinical and radiological characteristics correlated with these mutations were assessed. Furthermore, the effect of these mutations on the first symptomatic intraparenchymal hemorrhage during follow-up was evaluated. In total, 72 patients were included; among them, 50 had sufficient mutation data. PIK3CA E542K, E545K, and H1047R mutations were identified in 7 (14%), 7 (14%), and 15 (30%) patients, respectively. MAP3K3 I441M was identified in 10 (20%) patients (8 [16%] had both PIK3CA and MAP3K3 mutations). MAP3K3 I441M was more common in patients with Zabramski classification type II lesions than in those with CMs of other types (p = 0.024). Multivariate Cox regression analyses identified the presence of a PIK3CA mutation as a risk factor for early (re)hemorrhage. The results suggest that PIK3CA and MAP3K3 mutations are associated with clinical and radiological characteristics in patients with CMs and that the presence of a somatic PIK3CA mutation increases susceptibility to hemorrhage. These findings may help guide future therapeutic strategies.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of VEGF-C-Induced Dural Lymphatic Vessel Growth on Ischemic Stroke Pathology.","authors":"Meike Hedwig Keuters, Salli Antila, Riikka Immonen, Lidiia Plotnikova, Sara Wojciechowski, Sarka Lehtonen, Kari Alitalo, Jari Koistinaho, Hiramani Dhungana","doi":"10.1007/s12975-024-01262-9","DOIUrl":"10.1007/s12975-024-01262-9","url":null,"abstract":"<p><p>Timely relief of edema and clearance of waste products, as well as promotion of anti-inflammatory immune responses, reduce ischemic stroke pathology, and attenuate harmful long-term effects post-stroke. The discovery of an extensive and functional lymphatic vessel system in the outermost meningeal layer, dura mater, has opened up new possibilities to facilitate post-stroke recovery by inducing dural lymphatic vessel (dLV) growth via a single injection of a vector encoding vascular endothelial growth factor C (VEGF-C). In the present study, we aimed to improve post-stroke outcomes by inducing dLV growth in mice. We injected mice with a single intracerebroventricular dose of adeno-associated viral particles encoding VEGF-C before subjecting them to transient middle cerebral artery occlusion (tMCAo). Behavioral testing, Gadolinium (Gd) contrast agent-enhanced magnetic resonance imaging (MRI), and immunohistochemical analysis were performed to define the impact of VEGF-C on the post-stroke outcome. VEGF-C improved stroke-induced behavioral deficits, such as gait disturbances and neurological deficits, ameliorated post-stroke inflammation, and enhanced an alternative glial immune response. Importantly, VEGF-C treatment increased the drainage of brain interstitial fluid (ISF) and cerebrospinal fluid (CSF), as shown by Gd-enhanced MRI. These outcomes were closely associated with an increase in the growth of dLVs around the region where we observed increased vefgc mRNA expression within the brain, including the olfactory bulb, cortex, and cerebellum. Strikingly, VEGF-C-treated ischemic mice exhibited a faster and stronger Gd-signal accumulation in ischemic core area and an enhanced fluid outflow via the cribriform plate. In conclusion, the VEGF-C-induced dLV growth improved the overall outcome post-stroke, indicating that VEGF-C has potential to be included in the treatment strategies of post-ischemic stroke. However, to maximize the therapeutic potential of VEGF-C treatment, further studies on the impact of an enhanced dural lymphatic system at clinically relevant time points are essential.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"781-799"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141187012","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}

{"title":"Protease-Activated Receptors (PARs): Biology and Therapeutic Potential in Perioperative Stroke.","authors":"Theodoros Mavridis, Theodora Choratta, Androniki Papadopoulou, Assaf Sawafta, Paraschos Archontakis-Barakakis, Eleni Laou, Minas Sakellakis, Athanasios Chalkias","doi":"10.1007/s12975-024-01233-0","DOIUrl":"10.1007/s12975-024-01233-0","url":null,"abstract":"<p><p>Perioperative stroke is a devastating complication that occurs during surgery or within 30 days following the surgical procedure. Its prevalence ranges from 0.08 to 10% although it is most likely an underestimation, as sedatives and narcotics can substantially mask symptomatology and clinical presentation. Understanding the underlying pathophysiology and identifying potential therapeutic targets are of paramount importance. Protease-activated receptors (PARs), a unique family of G-protein-coupled receptors, are widely expressed throughout the human body and play essential roles in various physiological and pathological processes. This review elucidates the biology and significance of PARs, outlining their diverse functions in health and disease, and their intricate involvement in cerebrovascular (patho)physiology and neuroprotection. PARs exhibit a dual role in cerebral ischemia, which underscores their potential as therapeutic targets to mitigate the devastating effects of stroke in surgical patients.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"933-951"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703524","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":"Evolving Therapeutic Landscape of Intracerebral Hemorrhage: Emerging Cutting-Edge Advancements in Surgical Robots, Regenerative Medicine, and Neurorehabilitation Techniques.","authors":"Danyang Chen, Zhixian Zhao, Shenglun Zhang, Shiling Chen, Xuan Wu, Jian Shi, Na Liu, Chao Pan, Yingxin Tang, Cai Meng, Xingwei Zhao, Bo Tao, Wenjie Liu, Diansheng Chen, Han Ding, Ping Zhang, Zhouping Tang","doi":"10.1007/s12975-024-01244-x","DOIUrl":"10.1007/s12975-024-01244-x","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is the most serious form of stroke and has limited available therapeutic options. As knowledge on ICH rapidly develops, cutting-edge techniques in the fields of surgical robots, regenerative medicine, and neurorehabilitation may revolutionize ICH treatment. However, these new advances still must be translated into clinical practice. In this review, we examined several emerging therapeutic strategies and their major challenges in managing ICH, with a particular focus on innovative therapies involving robot-assisted minimally invasive surgery, stem cell transplantation, in situ neuronal reprogramming, and brain-computer interfaces. Despite the limited expansion of the drug armamentarium for ICH over the past few decades, the judicious selection of more efficacious therapeutic modalities and the exploration of multimodal combination therapies represent opportunities to improve patient prognoses after ICH.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"975-989"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336881","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}

{"title":"Complement Inhibition Reduces Early Erythrolysis, Attenuates Brain Injury, Hydrocephalus, and Iron Accumulation after Intraventricular Hemorrhage in Aged Rats.","authors":"Tianjie Zhang, Fan Xia, Yingfeng Wan, Guohua Xi, Hua Ya, Richard F Keep","doi":"10.1007/s12975-024-01273-6","DOIUrl":"10.1007/s12975-024-01273-6","url":null,"abstract":"<p><p>Blood components released by erythrolysis play an important role in secondary brain injury and posthemorrhagic hydrocephalus (PHH) after intraventricular hemorrhage (IVH). The current study examined the impact of N-acetylheparin (NAH), a complement inhibitor, on early erythrolysis, PHH and iron accumulation in aged rats following IVH. This study, on 18-months-old male Fischer 344 rats, was in 3 parts. First, rats had an intracerebroventricular injection of autologous blood (IVH) mixed with NAH or saline, or saline alone. After MRI at four hours, Western blot and immunohistochemistry examined complement activation and electron microscopy choroid plexus and periventricular damage. Second, rats had an IVH with NAH or vehicle, or saline. Rats underwent serial MRI at 4 h and 1 day to assess ventricular volume and erythrolysis. Immunohistochemistry and H&E staining examined secondary brain injury. Third, rats had an IVH with NAH or vehicle. Serial MRIs on day 1 and 28 assessed ventricular volume and iron accumulation. H&E staining and immunofluorescence evaluated choroid plexus phagocytes. Complement activation was found 4 h after IVH, and co-injection of NAH inhibited that activation. NAH administration attenuated erythrolysis, reduced ventricular volume, alleviated periventricular and choroid plexus injury at 4 h and 1 day after IVH. NAH decreased iron accumulation, the number of choroid plexus phagocytes, and attenuated hydrocephalus at 28 days after IVH. Inhibiting complement can reduce early erythrolysis, attenuates hydrocephalus and iron accumulation after IVH in aged animals.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"882-895"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470963","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}