Translational Stroke Research
·
2014
·Vol. 6
·期 2
·125-132
·
IF 1.938
Chen Qianwei,Zhang Jianbo,Guo Jing,Tang Jun,Tao Yihao,Li Lin,Feng Hua,Chen Zhi
Primary spontaneous intracerebral hemorrhage (ICH) with secondary intraventricular hemorrhage (IVH) is an important clinical problem of which little is known. IVH and hydrocephalus are independent predictors of poor outcome in ICH. The aims of this study were, therefore, to establish a rat model of ICH with ventricular extension and investigate the occurrence of post-hemorrhagic chronic hydrocephalus and perihematomal tissue injury. Based on our previous rat model of IVH, we adjusted the injection coordinates and 200 μl autologous blood was stereotaxically infused into the right striatum (coordinates: 0.2 mm posterior, 2.2 mm lateral, and 5.0 mm depth to the bregma). At 24 h post-infusion, the rats produced reproducible hematoma and ventricle expansion, which closely mimics the ICH with ventricular extension in humans. Hematoma consequences and perihematomal tissue injury were evaluated on the acute phase. At 4 weeks, ventricular dilatation, brain tissue loss, hippocampus volume, and cortical thickness were measured with magnetic resonance imaging and neurocognitive function was assessed using the Morris water maze test. With blood infusion, the animals demonstrated brain edema, blood–brain barrier breakdown, and marked perihematomal tissue injury on the acute phase. At 4 weeks, the T2 images showed remarkable hydrocephalus and tissue loss, and the Morris water maze test revealed neurocognitive deficits. The present ICH with the ventricular extension rat model features characteristics of both ICH and IVH rat models, which could be used for extending our pathophysiological understanding of post-hemorrhagic chronic hydrocephalus and perihematomal tissue damage.
研究领域:
神经科学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 16
·8509
·
IF 13.3
Tao Liu,Peng Ma,Fengya Jing,Yinghua Tao,Jinfang Lu,Dandan Wei,Liuxin Yang,Feiling Feng,Yonghua Li,Hongbin Yuan,Tianzhu Zhang
Background: The development of hemostatic materials for non-compressible intra-abdominal hemorrhage in complex pre-hospital emergency settings remains a formidable challenge. Methods: A novel injectable hydrogel based on mussel-inspired nanocomposite microspheres was designed. The biocompatible hydrogel was formed by hydrating gelatin methacryloyl (GelMA) cryogel microspheres—reinforced with polydopamine (PDA)-intercalated nanoclay—with sterile saline, offering the dual benefits of convenient storage of microspheres and precise delivery to deep bleeding points via injection. Results: The cryogel microspheres, featuring rapid water and blood absorption within 1 second, exhibited outstanding procoagulant capabilities in both in vitro and in vivo experiments, showing potential as hemostatic agents for open wounds. Notably, the on-demand formulated hydrogel effectively controlled severe bleeding within 2 minutes post-injection in rat liver volumetric defect and partial resection models, demonstrating significantly enhanced applicability compared to bulk hemostatic agents for irregular wounds. Additionally, ultrasound-guided application in a porcine liver rupture model confirmed that the hydrogel rapidly filled and sealed deep wounds, interacted with blood components to form stable, large clots adhering to the wound surface, and thus established durable hemostasis. Conclusion: This study presents a promising injectable hemostatic material for pre-hospital emergency hemorrhage control.
研究领域:
生物医学工程
·
创伤医学
·
再生医学
·
纳米医学
·
止血学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROMOLECULAR MEDICINE
·
2022
·Vol. 25
·期 1
·53-63
·
IF 4.103
Cheng Jing,Fan Yan-Qin,Zhang Wen-Fei,Zhang Guo,Zeng Kuo,Ye Zhang,Zhao Dan,Wu Li-Quan,Chen Zhi-Biao
Sirtuin-6 (SIRT6), a member of the sirtuins family of NAD ( +) dependent deacetylases, has been shown to have beneficial effects in ischemic stroke. However, the role of SIRT6 in intracerebral haemorrhage (ICH) has not reported. We observed that SIRT6 expression was down-regulated in human ICH patients and down-regulated in ICH-induced rat cortical neurons. We subsequently found that SIRT6 overexpression reduced brain tissue damage and increased neuronal survival in the ICH model of rats and hemin-induced cortical neurons. Our further study found that overexpression of SIRT6 can reduce inflammatory response by down-regulating the expression of NF-kB and thus promote the recovery of neurological function in ICH animals. In conclusion, SIRT6 can inhibit the expression of NF-kB and plays a neuroprotective role in ICH by inhibiting the NF-kB-mediated inflammatory response.SIRT6 could be a novel therapeutic target for ICH.
研究领域:
神经科学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2024
·Vol. 141
·期 34
·e55859
·
IF 2.7
Jian Wu,Shihao Zhou,Kai Lv,Wu Zhang,Yi Zhang,Hang Li,Dong Ma
Uncontrollable bleeding caused by accidental severe trauma and organ operation severely affects people's life safety, even leading to death. Therefore, it is important to cease the bleeding quickly and effectively. Here, we report a rapid photocrosslinking hydrogel (DP-F127 hydrogel) based on F127 and acrylate functional motifs for in situ emergency hemostasis. The acrylate groups in DP-F127 can be cross-linked within 10 s by UV irradiation. The resulted hydrogels exhibit excellent mechanical properties, biocompatibility, and rapid hemostatic ability. The in vivo studies on the DP-F127 hydrogel demonstrated that liver bleeding could be rapidly repaired and show significantly less blood loss than commercially available dressing (Gelatin sponge, GS). This study provides a new paradigm for developing a hemostatic hydrogel with the rapid speed of crosslinking for in situ emergency hemostasis.
研究领域:
生物材料
·
组织工程
·
止血
✓ 已验证
产品关联
DOI
高影响因子
Brain Hemorrhages
·
2025
·
IF 1.4
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.
研究领域:
神经科学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
BRAIN RESEARCH BULLETIN
·
2025
·
IF 3.7
Qiyu Yang,Chunyan Wang,Jingwei Cao,Zhanbin Tang,Shurong Duan
Intracerebral hemorrhage (ICH) is associated with the highest rates of mortality and residual disability. To date, effective treatments to delay or prevent ICH are still lacking. Multiple forms of neuronal cell death have been discovered following ICH, including apoptosis, necrosis, autophagy, and ferroptosis. Aldo-keto reductase family 1 member C1 (AKR1C1) has been identified to act as a protective factor in ferroptosis. However, whether AKR1C1 was involved in the development of ICH was unknown. In this study, the left cerebral striatum of the Sprague-Dawley rat was injected with collagenase type IV to induce an in vivo model. Primary rat cortical neurons treated with oxygen hemoglobin (OxyHb) were applied to as an in vitro model. AKR1C1 was found to be downregulated and immunoreactivity colocalized with NeuN-positive neurons in the perihematomal region. Rats injected with lentiviral particles overexpressing AKR1C1 showed the reduction of cerebral hematoma and the remission of blood-brain barrier disruption. Moreover, AKR1C1 upregulation repressed cell apoptosis and ferroptosis induced by ICH through downregulating the expression of pro-apoptotic factors, inhibiting iron accumulation and lipid peroxidation, along with increasing the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). The results of in vitro assays were consistent with results from the in vivo . Mechanistically, P53 overexpression augmented the cellular damage in OxyHb-stimulated neurons when AKR1C1 was overexpressed. Taken together, AKR1C1 improves ICH injury by inhibiting neuronal cell death via negatively regulating P53 expression and affecting the SLC7A11/GPX4 pathway.
研究领域:
神经科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Integrative Neuroscience
·
2025
·Vol. 24
·期 5
·26971
·
IF 2.7
Xue Lai,Yu Xiong,Xing Guo,Chunbo Chen
Objectives:Polybutylcyanoacrylate (PBCA) nanoparticles (NPs) were prepared by emulsion polymerization and loaded with an enhanced green fluorescent protein plasmid (pEGFP) encoding human brain-derived neurotrophic factor (BDNF). This study investigated the potential effects of PBCA-pEGFP-BDNF NPs for the treatment of experimental cerebral hemorrhage mouse model animals.Methods:Eight-week-old male mice (30 ± 5 g) were randomly divided into four groups (sham, intracerebral hemorrhage (ICH), ICH+PBCA NPs, and ICH+ PBCA-pEGFP-BDNF NPs; n = 14). An ICH model was constructed by right striatum injection of bacterial collagenase VII. Neurological function was evaluated by modified Garcia score after treatment of ICH mice with PBCA-pEGFP-BDNF NPs. The area of cerebral hematoma was measured and the water content of brain tissues was calculated by the wet/dry ratio method. Finally, immunofluorescence staining was used to detect neuron-specific nuclear protein (NeuN) positive cells around hematomas. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and western blot were used to detect inflammatory BDNF, nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and either interleukin-1 beta (IL-1β) mRNA or protein levels.Results:Treatment with PBCA-pEGFP-BDNF NPs significantly improved neurological function and reduced acute brain edema and neuroinflammation in the mouse model of ICH. qPCR, ELISA, and western blot results showed that PBCA-pEGFP-BDNF NPs increased BDNF expression, inhibited NF-κB signaling pathway activity, and decreased the levels of inflammatory factors (IL-6, TNF-α, IL-1β) when compared with the recombinant plasmid pEGFP-BDNF.Conclusion:PBCA-pEGFP-BDNF NPs improves neurological function in experimental ICH mice at least in part related to increased BDNF expression and decreased p65 NF-κB signaling axis activation, suggesting that PBCA NPs might be a suitable pEGFP-BDNF-carrying delivery system for ICH treatment.
研究领域:
神经科学
·
药剂学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·
IF 5.228
Hengli Zhao,Xuan Zhang,Zhiqiang Dai,Yang Feng,Qiang Li,John H. Zhang,Xin Liu,Yujie Chen,Hua Feng
Blockading P2X7 receptor(P2X7R) provides neuroprotection toward various neurological disorders, including stroke, traumatic brain injury, and subarachnoid hemorrhage. However, whether and how P2X7 receptor suppression protects blood-brain barrier(BBB) after intracerebral hemorrhage(ICH) remains unexplored. In present study, intrastriatal autologous-blood injection was used to mimic ICH in rats. Selective P2X7R inhibitor A438079, P2X7R agonist BzATP, and P2X7R siRNA were administrated to evaluate the effects of P2X7R suppression. Selective RhoA inhibitor C3 transferase was administered to clarify the involvement of RhoA. Post-assessments, including neurological deficits, Fluoro-Jade C staining, brain edema, Evans blue extravasation and fluorescence, western blot, RhoA activity assay and immunohistochemistry were performed. Then the key results were verified in collagenase induced ICH model. We found that endogenous P2X7R increased at 3 hrs after ICH with peak at 24 hrs, then returned to normal at 72 hrs after ICH. Enhanced immunoreactivity was observed on the neurovascular structure around hematoma at 24 hrs after ICH, along with perivascular astrocytes and endothelial cells. Both A438079 and P2X7R siRNA alleviated neurological deficits, brain edema, and BBB disruption after ICH, in association with RhoA activation and down-regulated endothelial junction proteins. However, BzATP abolished those effects. In addition, C3 transferase reduced brain injury and increased endothelial junction proteins' expression after ICH. These data indicated P2X7R suppression could preserve BBB integrity after ICH through inhibiting RhoA activation.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-14
·
IF 14.7
Ye Rui,Zhu Ziyu,Gu Tianyi,Cao Dengjie,Jiang Kai,Dai Qiang,Xing Kuoran,Jiang Yifan,Zhou Siyi,Cai Ping,Leong David Tai,Yu Mengfei,Song Jie
Severe traumatic bleeding may lead to extremely high mortality rates, and early intervention to stop bleeding plays as a critical role in saving lives. However, rapid hemostasis in deep non-compressible trauma using a highly water-absorbent hydrogel, combined with strong tissue adhesion and bionic procoagulant mechanism, remains a challenge. In this study, a DNA hydrogel (DNAgel) network composed of natural nucleic acids with rapid water absorption, high swelling and instant tissue adhesion is reported, like a band-aid to physically stop bleeding. The excellent swelling behavior and robust mechanical performance, meanwhile, enable the DNAgel band-aid to fill the defect cavity and exert pressure on the bleeding vessels, thereby achieving compression hemostasis for deep tissue bleeding sites. The neutrophil extracellular traps (NETs)-inspired DNAgel network also acts as an artificial DNA scaffold for erythrocytes to adhere and aggregate, and activates platelets, promoting coagulation cascade in a bionic way. The DNAgel achieves lower blood loss than commercial gelatin sponge (GS) in male rat trauma models. In vivo evaluation in a full-thickness skin incision model also demonstrates the ability of DNAgel for promoting wound healing. Overall, the DNAgel band-aid with great hemostatic capacity is a promising candidate for rapid hemostasis and wound healing.
研究领域:
生物材料
·
止血
·
组织工程
·
伤口愈合
✓ 已验证
DOI
PubMed
高影响因子
NEUROTOXICITY RESEARCH
·
2022
·Vol. 40
·期 1
·78-88
·
IF 3.978
Ji Na,Wu Lirong,Shi Hui,Li Qianlu,Yu Anyong,Yang Zhao
Intracerebral hemorrhage (ICH) is a fatal cerebrovascular disease. Neuroinflammation plays an important pathological role in brain injury after ICH. NLRP3 contributes to the pathogenesis of ICH, but the underlying mechanisms regulating of NLRP3 remain elusive. V-set and immunoglobulin domain containing 4 (VSIG4), specifically expressed in resting tissue-resident macrophages, can deliver anti-inflammatory signals into various inflammatory diseases. However, the interaction between VSIG4 and NLRP3, as well as the underlying mechanisms after ICH have not been reported. C57BL/6 mice were subjected to the autologous blood injection ICH model. VSIG4 and NLRP3 levels of macrophages were detected following ICH. Ad-VSIG4 or controls were administered via intracerebroventricular (i.c.v) injection before ICH induction. STAT3 inhibitor (S31-201), JAK2 inhibitor (TG101348), or Ad-A20 RNAi was administered to investigate the role of JAK2-STAT3-A20 pathway in VSIG4-mediated neuroinflammation after ICH. Pro-inflammatory cytokine production, BBB disruption, brain water content, and neurological test were examined in ICH mice. VSIG4 levels were significantly decreased, and NLRP3 levels were significantly increased in the perihematomal brain tissues after ICH. Ad-VSIG4 attenuated NLRP3 levels and inhibited inflammation, as well as improved neurological function and reduced BBB disruption and brain water content. Furthermore, Ad-VSIG4 increased the protein levels of phosphorylated JAK2 and STAT3, and A20 levels at 24 h after ICH. STAT3 inhibitor, JAK2 inhibitor, and A20 RNAi abolished the beneficial effects of Ad-VSIG4 after ICH. In summary, these data suggested that VSIG4 attenuated NLRP3 and ameliorated neuroinflammation via JAK2-STAT3-A20 pathway after intracerebral hemorrhage in mice. VSIG4 might be an ideal therapeutic target for ICH patients.
研究领域:
神经科学
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2021
·
IF 0
Wen Liu,Xiao Yang,Pengpeng Li,Feng Sang,Lina Cao,Bingxu Zhang,Zhizhen Meng,Zhaipu Ma,Changcan Shi
Uncontrollable hemorrhage, especially uncompressible and massive hemorrhage, is life threatening. To develop a kind of hemostatic material that is biocompatible and has effective hemostatic performance, a starch-polyethylene glycol sponge (St-PEG sponge) incorporated with electrospraying microspheres made from carboxymethyl chitosan and sodium alginate (CMC/SA eMPs) is employed to fabricate the topical hemostatic agent for application. To load thrombin safely and effectively, CMC/SA eMPs encapsulating thrombin compounds (eMPs@Thr) are further incorporated with St-PEG sponge to obtain eMPs@Thr/sponge. The results show that eMPs@Thr/sponge could obviously reduce blood loss and shorten the hemostatis time compared with commercial hemostatic products Kuai Kang. The construction of the eMPs@Thr/sponge could not only maintain the expandable properties of the St-PEG sponge but also strengthen the procoagulant activity. Therefore, this work provides a facile approach for loading thrombin given the fact that thrombin suffers from instability and risk of thrombus. It is predicted that eMPs@Thr/sponge might hold great potential in uncompressible and massive hemorrhage control.
研究领域:
生物材料
·
止血
·
生物医学工程
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
BIOMATERIALS
·
2025
·
IF 12.9
Xiumei Guo,Qionghua Zheng,Wen Gao,Yinfeng Xiao,Liyong Shi,Fenglin Lin,Yu Xiong,Yin Zhang,Qiuxia Xu,Lingxing Wang,Shaobin He,Feng Zheng
Abnormal microglial activation increases inflammation, causing significant brain damage after intracerebral hemorrhage (ICH). To aid recovery, treatments should regulate oxidative stress and inhibit the M1-like phenotype (pro-inflammation) of microglia. Recently, antioxidant nanozymes have emerged as tools for modulating microglial states, but detailed studies on their role in ICH treatment are limited. To address this, we developed an ultra-small (3–4 nm) laminarin-modified platinum nanozyme (Pt@LA) for the synergistic regulation of microglial polarization, offering a novel therapeutic strategy for ICH. Pt@LA effectively scavenges reactive oxygen species (ROS) through superoxide dismutase (SOD) and catalase (CAT)-like activities. Laminarin may inhibit the Dectin-1 receptor on microglia and its inflammatory pathway, Syk/NF-κB, reducing neuroinflammation. In vitro, Pt@LA decreased pro-inflammatory microglia and cytokine expression by inhibiting the Dectin-1/Syk/NF-κB and ROS-mediated NF-κB pathways. Furthermore, Pt@LA protected neurons, inhibited glial scar formation, and improved neurological function in ICH rats. Overall, this study presents Pt nanozymes based on naturally extracted laminarin and explores their application in alleviating oxidative stress and neuroinflammation after ICH, bridging nanozyme research and neuroscience.
研究领域:
神经科学
·
药理学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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