ACS Applied Materials & Interfaces
·
2021
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IF 9.229
Haoyuan Li,Zhipeng Yang,Qisheng Tang,Zhifeng Shi,Ying Mao
Stroke models are vital tools in neuropharmacology and rehabilitation research. However, a classic and widely used model—the suture occlusion model—is not suitable for all research approaches, especially regarding thrombolysis. For embolic stroke models in thrombolytic research, the surgical procedures of thrombin injection in the middle cerebral artery or clot injection in the carotid artery involved are too sophisticated. Here, we report a new stroke model in mice that uses magnetic nanoparticle (MNP) cross-linked with thrombin to embolize. Briefly, after the magnet was positioned in the common carotid artery, MNP@Thrombin was injected from the tail vein. Within several minutes postinjection, the MNP@Thrombin accumulated in the carotid artery and induced thrombus formation. These complex clots were flushed into and subsequently blocked the cerebral artery. Collectively, these results suggested that this new method was a quick and easy stroke model that blocked hemisphere blood flow and damaged neural function. Importantly, this model had an excellent response to thrombolytic drugs. After urokinase injection, cerebral blood flow was restored and symptom scores were enhanced by nearly one. This method, including a quick synthesis of MNP and thrombin, provided an easy and minimally invasive process for a new stroke model that is usable in both pharmacological and rehabilitative research.
研究领域:
神经药理学
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康复研究
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中风模型
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溶栓
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
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IF 6.7
Wendi Wang,Qing Han,Tianwei Wang,Jian Liu,Qingbin Ni,Jingyi Sun,Ying Wang,Baoliang Sun
Ischemic stroke (IS) has a high mortality rate. Multiplexed detection of IS core biomarkers is of great significance to early diagnosis and personalized treatment of IS patients. Whether pericytes, a key component of the neurovascular unit and blood-brain barrier located on the capillary wall, could serve as a promising biomarker for IS is to be explored. Herein, we observed a significant upregulation of inflammatory and apoptotic factors, such as MMP9, in pericytes subjected to in vitro ischemia. By transfecting pericytes with ASK1-shRNA to inhibit ASK1 expression, we noted reduced levels of inflammatory and apoptotic markers, including MMP9, as well as enhanced pericyte contraction and migration, thereby preserving the integrity of the blood-brain barrier. Additionally, ELISA assays conducted using plasma samples from patients with varying NIHSS scores revealed statistically significant concentrations of PDGFRβ and MMP9. Furthermore, we developed a highly sensitive and specific quantitative detection method for PDGFRβ and MMP9 based on fluorescence sensor technology. This novel detector exhibits high sensitivity, repeatability, and stability, enabling precise dual detection. Thus, the results suggest the great potential of the detection of PDGFRβ and MMP9 for early diagnosis of IS and prognosis prediction of the disease.
研究领域:
神经科学
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医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
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2025
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IF 5.4
Ling-Kun Zhang,Li Liu,Ziqing Li,Yiquan Zhang,Limin Zhai,Luna Zhang,Chu-Hua Li,Yan-Qing Guan
Cerebral ischemic stroke, neuronal death, and inflammation bring difficulties in neuroprotection and rehabilitation. In this study, we developed and designed the ability of natural lactoferrin-polyethylene glycol-polyphenylalanine-baicalein nanomicelles (LF-PEG-PPhe-Bai) to target and reduce these pathological processes, such as neurological damage and cognitive impairment in the stages of poststroke. Nanomicelles made from biocompatible materials have improved bioavailability and targeted distribution to afflicted brain areas. The results showed that LF-PEG-PPhe-Bai greatly improved the antioxidation, antiapoptosis, and anti-inflammation activity in vitro. Meanwhile, LF-PEG-PPhe-Bai improved the behavioral and cognitive impairment of 2-VO model mice, protected nerve cells in the hippocampus, and reduced inflammation at the brain injury site in vivo. In conclusion, LF-PEG-PPhe-Bai nanomicelles are employed for enhancing neuroprotection and poststroke rehabilitation. The development of this technology might provide a new technique for neural repair after ischemia in the future.
研究领域:
神经科学
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药学
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生物材料学
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DOI
PubMed
高影响因子
Scientific Reports
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2025
·Vol. 15
·期 1
·1-14
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IF 3.9
Sun Jinzhou,Chen Qianqian,Zhuang Chumeng,Li Xiaohong,Yu Li,Jin Weifeng
Develop a novel coupled PK-PD model and apply it to quantitatively evaluate the synergistic effects of Hydroxysafflor Yellow A (HSYA) combined with Calycosin (CA) in the treatment of ischemic stroke. A total of 6 rats were modelled for middle cerebral artery occlusion (MCAO). Plasma was collected from the submandibular venous plexus of rats after the administration of HSYA and CA, and was detected and analyzed by LC-MS method. The plasma expression levels of Caspase-9, IL-1β and SOD in rats were also determined by ELISA kit. Meanwhile, a coupled PK-PD model was proposed, incorporating interaction terms between drugs and coupling of pharmacodynamic effects, to quantitatively reveal their interactions. Moreover, a numerical solution technique based on optimization methods was proposed, enabling the model to be effectively applied to experimental data. Based on the coupled PK model, HSYA and CA significantly increased each other’s metabolic rates. The model also showed that CA had a larger apparent volume of distribution and clearance in rats, while HSYA had a shorter mean retention time and elimination half-life. The coupled PK-PD model indicated a synergistic effect between HSYA and CA on all three pharmacodynamic markers, with HSYA contributing more significantly. Despite individual variability among the six rats, the parameter interpretations remained consistent. The proposed coupled PK-PD model and its numerical solution algorithm successfully revealed the synergistic effects of HSYA and CA in the treatment of ischemic stroke. This model lays the foundation for future models with more complex interactions and effects.
研究领域:
药理学
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生物医学工程
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神经科学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL NEUROLOGY
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2021
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IF 5.33
Mengmeng Wang,Ying Bai,Haitao Chi,Ping Lin,Yu Wu,Jiahui Cui,Yi Wang,Jing Sun,Ming-Fei Lang
Ischemic stroke still remains a therapeutic challenge due to its complex pathogenesis and implications. By screening biomarkers in the peripheral blood of ischemic stroke patients , miR-451 was identified as a differentially expressed miRNA along the disease course of ischemic stroke. To investigate the role of miR-451, middle cerebral artery occlusion (MCAO) was performed as an ischemic stroke model in mice. Intracerebroventricular administration of miR-451 mimic in the MCAO mice significantly decreased infarct size, while miR-451 inhibitor significantly increased infarct size. To understand the molecular mechanism of the protective effect of miR-451, Phd3 (also Egln3) was validated as a new miR-451 target. Either fewer or more Phd3-positive cells were observed in brain sections from mice receiving miR-451 mimic or inhibitor, respectively. In addition, the levels of p53 (a known Phd3 target) were significantly downregulated when the levels of Phd3 were reduced, suggesting its participation in reducing apoptosis after the miR-451 administration. Indeed, reduced apoptosis upon miR-451 mimic administration was detected by TUNEL staining . In conclusion, this study demonstrated a new protective role of miR-451 in cerebral ischemia and identified Phd3 as a novel miR-451 target, linking the mechanism to the involvement of p53 in the regulation of apoptosis during the pathogenesis of ischemic stroke.
研究领域:
神经科学
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分子生物学
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医学遗传学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2023
·Vol. 24
·期 3
·2126
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IF 5.6
Shouchao Xu,Jiehong Yang,Haitong Wan,Li Yu,Yu He
Promotion of angiogenesis and restoration of the blood flow in the ischemic penumbra is an effective treatment for patients with ischemic stroke (IS). Radix astragali-safflower (AS), a classic herbal pair for accelerating blood circulation and dispersing blood stasis, has been used for thousands of years to treat patients with IS in China. Even so, the mechanism of the treatment of IS by AS is still undecipherable. In the current study, network pharmacology was firstly employed to unveil the mechanism of AS in treating IS, which showed that AS might promote angiogenesis associated with PTGS2 silence. Middle cerebral artery occlusion/reperfusion (MCAO/R) model rats were then used as the experimental animals to verify the prediction result. The experimental results revealed that treatment with AS improved the cerebral infarct volume, neurological damage, and cerebral histopathological damage; inhibited cell apoptosis; increased the contents of PDGF-BB, EPO, and TGF-β1; and reduced the levels of PF4, Ang-2, and TIMP-1 in serum. Immunohistochemical staining demonstrated that the expression of PTGS2 was dramatically increased in the hippocampus and cerebral cortex of rats with MCAO/R, and this trend was reversed by the treatment of AS. Immunofluorescent staining expressed that AS reversed the down-regulation of VEGF and further promoted the expression of CD31, which indicated that AS promoted angiogenesis in MCAO/R rats. The abnormal protein or mRNA expression of PTGS2, PGI2, bFGF, TSP-1, and VEGF in the penumbra were transposed by AS or Celecoxib (an inhibitor of PTGS2). In conclusion, the protective mechanism of AS for IS promoted angiogenesis and was involved with PTGS2 silence.Keywords:Radix astragali and safflower;angiogenesis;ischemic stroke;ischemic penumbra;PTGS2
研究领域:
药理学
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神经科学
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中医药学
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产品关联
DOI
PubMed
高影响因子
ACS Chemical Neuroscience
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2023
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IF 5
Ye Xiong,Yanqiong Fu,Zhuoli Li,Yu Zheng,Maiyin Cui,Chan Zhang,Xin Yi Huang,Yong Jian,Bai Hui Chen
Glial activation is involved in neuroinflammation and blood–brain barrier (BBB) damage, which plays a key role in ischemic stroke-induced neuronal damage; therefore, regulating glial activation is an important way to inhibit ischemic brain injury. Effects of laquinimod (LAQ) include inhibiting axonal damage and neuroinflammation in multiple neuronal injury diseases. However, whether laquinimod can exert neuroprotective effects after ischemic stroke remains unknown. In this study, we investigated the effect of LAQ on glial activation, BBB damage, and neuronal damage in an ischemic stroke model. Adult ICR mice were used to create a photothrombotic stroke (PT) model. LAQ was administered orally at 30 min after ischemic injury. Neurobehavioral tests, Evans Blue, immunofluorescence, TUNEL, Nissl staining, and western blot were performed to evaluate the neurofunctional outcome. Quantification of immunofluorescence was evaluated by unbiased stereology. LAQ post-treatment significantly reduced infarction and improved forepaw function at 5 days after PT. Interestingly, LAQ treatment significantly promoted anti-inflammatory microglial activation. Moreover, LAQ treatment reduced astrocyte activation, glial scar formation, and BBB breakdown in ischemic brains. Therefore, this study demonstrated that LAQ post-treatment restricted microglial polarization, astrogliosis, and glial scar and improved BBB damage and behavioral function. LAQ may serve as a novel target to develop new therapeutic agents for ischemic stroke.
研究领域:
神经科学
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药理学
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神经病学
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炎症
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产品关联
DOI
PubMed
高影响因子
NEUROMOLECULAR MEDICINE
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2025
·Vol. 27
·期 1
·1-14
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IF 3.9
Wang Yiming,Chen Yifei,Yang Jianbo,Sun Wei,Zhang Xiaoning
Post-stroke insomnia (PSI) is a common complication following stroke, which seriously affects patients’ life quality. Electro-acupuncture (EA) is an innovative form of traditional Chinese acupuncture that combines electricity with needles to achieve the prevention and treatment of diseases. However, there is limited understanding regarding the treatment mechanism of EA in PSI. In our study, we aimed to investigate the role of EA on PSI development. Our study findings indicated that the quality of sleep, levels of neurotransmitters 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (γ-GABA), and antioxidant levels showed significant improvement following EA treatment in PSI clinical samples and rat models, while the levels of pro-inflammatory factor interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and astrocyte damage were notably reduced. Furthermore, it was discovered that the levels of sirtuin 1 (Sirt1) were reduced in PSI, a condition that was significantly ameliorated by EA treatment. Additionally, the inhibition of Sirt1 caused a marked elevation in astrocyte apoptosis, inflammatory response, and oxidative stress. Besides, the nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway was deactivated in the PSI rat model and Sirt1-silenced cells. However, the suppressive impact was successfully counteracted by EA or estazolam (ES), and the overexpression of Nrf2 partially alleviated the increase in apoptosis, inflammation, and oxidative stress caused by Sirt1 knockdown. Taken together, these findings indicated that EA improved sleep quality and silenced Sirt1-induced apoptosis, inflammation, and oxidative stress in PSI by activating the Nrf2-ARE pathway.
研究领域:
神经科学
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中医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Yi-fan Li,Yue-fan Zhang,Can Huang,Jie-mei Jiang
Objective The inflammatory response is integral to all stages of ischemic stroke. Unlike conventional reperfusion therapies, anti-inflammatory strategies offer a broader therapeutic window for treating ischemic stroke due to their capacity to attenuate inflammation. Astrocytes, once activated in ischemic conditions, significantly contribute to the production of inflammatory cytokines and exacerbate brain damage. While the neuroprotective effects of baicalin in post-stroke patients have been recognized, its role in modulating astrocyte activity and reducing inflammation remains under debate. This study aims to evaluate the impact of baicalin on astrocyte activation following ischemic stroke. Methods A model of ischemia/reperfusion (I/R) injury was induced in wild-type mice through transient middle cerebral artery occlusion (tMCAO). Mice were randomized into groups receiving either baicalin or saline. The expression levels of inflammatory markers—interleukin (IL)-6, IL-1β, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-α)—were quantified using enzyme-linked immunosorbent assay (ELISA). Additionally, western blot analysis was employed to assess glial fibrillary acidic protein (GFAP) expression. Results Baicalin administration significantly mitigated neurological deficits in mice post-tMCAO. It reduced the activation of astrocytes and the production of pro-inflammatory cytokines such as IL-6, IL-1β, TNF-α, and MCP-1, observed both in vivo and in vitro. In vitro studies also indicated a suppression of NF-κB activation. Conclusion Baicalin effectively prevents ischemic brain damage by curtailing neuroinflammation and astrocyte activation. These findings advance the understanding of baicalin’s mechanistic role in mitigating brain ischemia and support further investigation into its therapeutic potential.
研究领域:
神经科学
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药理学
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产品关联
DOI
PubMed
高影响因子
Translational Stroke Research
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2025
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IF 4.3
Zhang Huiran,Tian Yanfei,Zhang Yan,Wang Yan,Qi Jinlong,Wang Xiangyu,Yuan Yi,Chen Rong,Zhao Yupeng,Liu Chang,Zhou Najing,Liu Lanxin,Hao Han,Du Xiaona,Zhang Hailin
Ischemic stroke is a worldwide disease with high mortality and morbidity. Kv7/KCNQ channels are key modulators of neuronal excitability and microglia function, and activation of Kv7/KCNQ channels has emerged as a potential therapeutic avenue for ischemic stroke. In the present study, we focused on a new Kv7/KCNQ channel opener QO-83 on the stroke outcomes and its therapeutic potential. Transient or distal middle cerebral artery occlusion model was established with C57 mouse to evaluate the role of QO-83. Solitary dose of QO-83 contributes to the microglia inhibition and fibrotic scar mitigation post stroke. QO83 shows prominent effect on reducing infarction area, alleviating cerebral edema, maintaining blood–brain barrier integrity, and enhancing neurogenesis. Single-nucleus RNA sequencing unveils neuroprotection and specific microglial subclusters influenced by QO-83. More importantly, QO83 shows promise in enhancing survival rates with dose dependence. Notably, these protective effects extend beyond the 4–6 h post-reperfusion window. Additionally, continuous dosing of QO-83 correlates with enhanced cognition. In conclusion, this study highlights QO-83 as a protective agent against ischemic brain injury, showcasing its multifaceted effects and potential as a therapeutic strategy.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2025
·Vol. 18
·期 4
·548
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IF 4.8
Huiming Xue,Zhen Feng,Chang Jin,Yue Zhang,Yongxing Ai,Jing Wang,Meizhu Zheng,Dongfang Shi
Objectives: Ischemic stroke is a severe neurological disorder with high morbidity, mortality, and disability rates, posing a substantial burden on patients, families, and healthcare systems. Soy isoflavone (SI), a naturally occurring phytoestrogen, has demonstrated promising neuroprotective effects. This study aimed to evaluate the anti-stroke efficacy of SI and elucidate its underlying mechanisms through integrated phytochemical profiling, network pharmacology, and both in vitro and in vivo experimental validation.Methods: Active constituents of SI were extracted via reflux and identified using liquid chromatography–mass spectrometry (LC-MS). Network pharmacology was employed to predict therapeutic targets and signaling pathways. The neuroprotective effects of SI were first assessed in PC12 cells subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) injury in vitro. For in vivo evaluation, transient cerebral ischemia–reperfusion injury was induced using the bilateral common carotid artery occlusion (BCCAO) model in adult male ICR rats (27.3 ± 1.8 g; 6–8 weeks old), obtained from the Shanghai Experimental Animal Center, Chinese Academy of Sciences. Forty-eight rats were randomly assigned into four groups (n= 12): sham, model (BCCAO), SI-treated (100 mg/kg, oral gavage for 5 days), and edaravone (EDA)-treated (10 mg/kg, i.p., positive control). All procedures were approved by the Institutional Animal Care and Use Committee of Changchun Normal University (Approval No. 2024003, 13 March 2024) and conducted in accordance with the NIH guidelines and ARRIVE 2.0 reporting standards.Results: In vitro, SI significantly enhanced PC12 cell viability from 57.23 ± 2.88% to 80.76 ± 4.43% following OGD/R. It also reduced intracellular Ca2+by 58.42%, lactate dehydrogenase (LDH) release by 37.67%, caspase-3 activity by 55.05%, and reactive oxygen species (ROS) levels by 74.13% (p< 0.05). A flow cytometry analysis revealed that OGD/R increased the apoptosis rate from 5.34% (control) to 30.85% (model group), which was significantly attenuated by SI treatment, especially in the 560 µg/mL group (20.00%), followed by the 140 and 280 µg/mL groups. In vivo, SI improved neurological scores from 8.3 ± 1.09 to 6.8 ± 1.68, reduced cerebral infarction volume by 18.49%, and alleviated brain edema by 10.42% (p< 0.05). SI also decreased malondialdehyde (MDA) and LDH levels by 31.15% and 39.46%, respectively, while increasing the activity of antioxidant enzymes: superoxide dismutase (SOD) by 11.70%, catalase (CAT) by 26.09%, and glutathione peroxidase (GSH-px) by 27.55% (p< 0.01). Scratch assay results showed that SI restored the impaired migratory ability of the OGD/R-treated PC12 cells, further supporting its role in cellular repair. A Western blot analysis demonstrated the upregulation of nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1) and the downregulation of Kelch-like, ECH-associated protein 1 (Keap1) in the cerebral ischemia–reperfusion model.Conclusions: These findings indicate that soy isoflavone confers significant neuroprotective effects against cerebral ischemia–reperfusion injury by enhancing endogenous antioxidant defense mechanisms, reducing oxidative stress, inhibiting apoptosis, and promoting cell migration. The protective effects are likely mediated through the activation of the Nrf2/Keap1 signaling pathway, supporting the therapeutic potential of SI in ischemic stroke treatment.
研究领域:
药理学
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神经科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Genes & Diseases
·
2025
·
IF 9.4
Hui Gan,Mi Zhang,Yuhao Duan,Palahati Ailiyaer,Qi He,Junyi Tan,Yong Li,Xuan Zhai,Jing Zhao
Microglial activation triggers the inflammatory cascade and exacerbates brain injury following ischemic stroke. Middle cerebral artery occlusion (MCAO) modeling increased the expression of nuclear factor of activated T cells 5 (NFAT5) in microglia. However, the role of microglial NFAT5 in ischemic stroke remains unclear. Here, our findings indicated that microglial NFAT5 knockdown reduced the expression of pro-inflammatory factors, microglial activation, and neutrophil infiltration, ultimately ameliorating cerebral infarction and neurological deficits in mice following MCAO. Additionally, we treated hippocampal neuronal cells (HT22) with a conditioned culture medium from a microglia cell line (BV2) to simulate microglia-induced neuronal injury in vitro . We observed that NFAT5 knockdown attenuated the expression of pro-inflammatory factors in BV2 cells and reduced apoptosis in HT22 cells. Previously, our published work reported that the NOD-like receptor pyrin domain-containing 6 (NLRP6) inflammasome contributed to inflammatory injury after MCAO. In this study, we discovered that NFAT5 promoted the transcriptional activity of the Nlrp6 promoter through its −1527 bp to −1518 bp element. Notably, our results also demonstrated that NFAT5 regulated the stability of NLRP6 mRNA via the 5'UTR of Nlrp6 . Thus, our findings reveal the pivotal role and partial mechanism of microglial NFAT5 in neuroinflammation following ischemic stroke.
研究领域:
神经科学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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