NEUROMOLECULAR MEDICINE
·
2022
·Vol. 25
·期 1
·53-63
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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
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产品关联
DOI
PubMed
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
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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
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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
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
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免疫学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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
Neurocritical Care
·
2021
·Vol. 35
·期 2
·367-378
·
IF 3.21
Li Yinghui,Ren Siying,Wang Likun,Mao Yuanhong,Wu Guofeng,Li Qi,Tang Zhouping
Background Blend sign on initial computed tomography (CT) is associated with poor outcome in patients with intracerebral hemorrhage (ICH). However, the mechanisms underlying the blend sign formation are poorly understood. The present study aimed to explore the possible mechanism of the CT blend sign in patients with ICH. Methods Seventy healthy rabbits were selected to prepare an ICH model. The animals were assigned to a whole blood group + whole blood group (ww group, 50 rabbits), a whole blood + plasma group (wp group, 10 rabbits) or a whole blood + serum group (ws group, 10 rabbits). The animals of the ww group were allocated to five subgroups based on the interval between the first infusion of blood and the second one. The subgroups included ww 1 h group (with an interval of 1 h), ww 2 h group, ww 3 h group, ww 4 h group and ww 5 h group. The rabbits from each group received first infusion of 0.3 mL of whole blood into the basal ganglia area to form a hematoma. Then, they received a second infusion of the same amount of whole blood, plasma or serum into the brain to form another hematoma adjacent to the first one. Results A hematoma with two densities on brain CT could be formed in each group after a second infusion of blood into the brain. A significant difference in CT attenuation values was observed between the hyperattenuation and the hypoattenuation in all the groups. However, only the morphological features of the hematoma in the ww group was in accordance with the CT blend sign observed in humans. The CT attenuation values in the hypodensity area of the ww 4 h group or the ww 5 h group were decreased compared with the ww 1 h group to the ww 3 h group. Conclusions The CT blend sign observed in humans might be composed of two parts of blood with different ages. The hypodense area might be blood with older age and the hyperdense area might be new bleeding.
研究领域:
医学影像学
·
神经病学
✓ 已验证
DOI
高影响因子
Frontiers in Neurology
·
2022
·
IF 4.086
Ren Siying,Han Shanshan,Wang Likun,Huang Yuanxin,Wu Jing,Wu Guofeng
Objective: To investigate the role of minimally invasive surgery (MIS) in intracerebral hemorrhage (ICH) evacuation combined with deferoxamine (DFX) treatment on perihematomal tight junction protein (claudin-5 and ZO-1) expression levels and blood-brain barrier (BBB) permeability in rabbits.Methods: We randomly assigned 65 male rabbits (weight: 1.9–2.6 kg) to a normal control group (NC group, 13 rabbits), hemorrhage model group (HM group, 13), DFX treatment group (DFX group, 13 rabbits), MIS group (MIS group, 13 rabbits), or MIS combined with DFX treatment group (MIS + DFX group, 13 rabbits). ICH was established in all of the groups except the NC group. MIS was performed to evacuate the hematoma 6 h after the ICH model was created in the MIS and MIS + DFX groups. The DFX and MIS + DFX groups were treated with DFX (100 mg/kg, dissolved in 2 mL of 0.9% saline solution, administered intramuscularly) at 2 h, and then every 12 h for 7 d. The same dose of 0.9% saline solution was administered to the NC, HM, and MIS groups at the same time points. Sixty-five rabbits were divided into 5 groups, and 13 rabbits in each group. Neurological deficit (i.e., Purdy's score) was recorded in all rabbits before euthanasia (N total = 65). In each group, 2 rabbits were used for iron concentration measurement (N total = 10), 2 rabbits were used for brain water content measurement (N total = 10), 3 rabbits were used for BBB permeability measurement (N total = 15), 3 rabbits were used for claudin-5, ZO-1 expression detection by Western Blotting (N total = 15), and 3 rabbits were used for claudin-5, ZO-1 mRNA detection by real-time PCR (N total = 15). On day 7, the rabbits were sacrificed and the perihematomal brain tissue was harvested to test the iron concentration, brain water content (BWC), tight junction proteins (claudin-5 and ZO-1) expression, and BBB permeability.Results: Purdy's score, iron concentration, and BWC were lower in the MIS and MIS + DFX groups compared to the HM and DFX groups. The MIS + DFX group showed a significant decrease in these indicators. The use of MIS to evacuate the hematoma led to increased expression levels of claudin-5 and ZO-1, as well as decreased BBB permeability. The MIS + DFX group exhibited a remarkable increase in claudin-5 and ZO-1 expression levels and a significant decrease in BBB permeability.Conclusions: MIS combined with DFX treatment could increase the expression levels of perihematomal tight junction proteins (claudin-5 and ZO-1) expression, reduce BBB permeability, and improve the neurological function. MIS combined with DFX treatment may also prevent secondary brain damage following ICH.
研究领域:
神经科学
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医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROIMMUNOMODULATION
·
2021
·Vol. 29
·期 4
·317-326
·
IF 2.492
Wu Xiuwen,Liu Xiaopeng,Yang Liang,Wang Yuanyu
Background: Elevation of AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) signaling can suppress intracerebral hemorrhage (ICH)-induced neurological impairments. As an isoquinoline alkaloid, Berberine exerts neuroprotective effects in neurological disease models with activated AMPK/PGC1α signaling. Aim: We aim to study the effect of Berberine on ICH-induced brain injury and explore the potential molecular mechanism. Methods: ICH model was established in mice through intracerebral injection of autologous whole blood, followed by treatment with Berberine. Neurological impairments were assessed by the modified neurological severity score and behavioral assays. Brain edema and blood-brain barrier (BBB) integrity were assessed by water content in the brain, amount of extravasated Evans blue, and BBB tight junction components. Neuroinflammatory responses were assessed by inflammatory cytokine levels. AMPK/PGC1α signaling was examined by AMPK mRNA expression and phosphorylated AMPK and PGC1α protein levels. Results: Berberine (200 mg/kg) attenuated ICH-induced neurological deficits, motor and cognitive impairment, and BBB disruption. Berberine also suppressed ICH-induced inflammatory responses indicated by reduced production of inflammatory cytokines. Finally, Berberine drastically elevated AMPK/PGC1α signaling in the hemisphere of ICH mice. Conclusion: Our findings suggest that Berberine plays an important neuroprotective role against ICH-induced neurological impairments and BBB injury, probably by inhibition of inflammation and activation of AMPK/PGC1α signaling
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
Biomedical Optics Express
·
2021
·Vol. 12
·期 6
·3643-3657
·
IF 3.732
Wenzhao Yang,Wenzhao Yang,Wei Wang,Wei Wang,Lili Jing,Lili Jing,Sung-Liang Chen,Sung-Liang Chen,Sung-Liang Chen,Sung-Liang Chen
The zebrafish has emerged as a useful model for human hematological disorders. Transgenic zebrafish that express green fluorescence protein (GFP) in red blood cells (RBCs) visualized by fluorescence microscopy (FLM) is a fundamental approach in such studies to understand the cellular processes and biological functions. However, additional and cumbersome efforts are required to breed a transgenic zebrafish line with reliable GFP expression. Further, the yolk autofluorescence and finite GFP fluorescence lifetimes also have an adverse impact on the observation of target signals. Here, we investigate the identification of intracerebral hemorrhage (ICH) and hemolytic anemia (HA) in zebrafish embryos using label-free photoacoustic microscopy (PAM) for imaging. First, ICH and HA in transgenic LCR-EGFP zebrafish are mainly studied by PAM and FLM. The results show that PAM is comparable to FLM in good identification of ICH and HA. Besides, PAM is more advantageous in circumventing the issue of autofluorescence. Secondly, ICH and HA in the transparent casper zebrafish without fluorescent labeling are imaged by PAM and bright-field microscopy (BFM). Because of the high contrast to reveal RBCs, PAM obviously outperforms BFM in the identification of both ICH and HA. Note that FLM cannot observe casper zebrafish due to its lack of fluorescent labeling. Our work proves that PAM can be a useful tool to study blood disorders in zebrafish, which has advantages: (i) Reliable results enabled by intrinsic absorption of RBCs; (ii) wide applicability to zebrafish strains (no requirement of a transgene); (iii) high sensitivity in identification of ICH and HA compared with BFM.
研究领域:
医学影像学
·
血液学
·
发育生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Wang Youwei,Chen Bing,Fan Jiang,Wang Zhong
Monitoring ferroptosis-related miRNAs is crucial for the treatment and prognosis of patients with intracerebral hemorrhage. In this work, a novel hydrophobic paper (h-paper)-based plasmonic substrate was produced by dropping DS Au nanorods with a narrow range of sizes and morphologies onto h-paper. Raman reporter molecules were adsorbed to the array surface, and surface-enhanced Raman scattering spectra at randomly selected points reveal uniform and significant SERS enhancement. Hairpin DNAs labelled with Raman reporters and hybridized with placeholder DNAs were decorated on SERS substrate to fabricate SERS biosensor. Target miRNAs initiated the “inverse Molecular Sentinel” process. During the process, PHs were removed and the conformation of HPs changed toward the hairpin structure, thus eliciting the proximity of Raman reporter to substrate and a stronger SERS signal. The proposed SERS biosensor performs well in terms of stability, reproducibility, and selectivity. The limits of detection of miR-122-5p and miR-140-5p in serum were 4.17 aM and 4.49 aM, respectively. Finally, the fabricated SERS biosensor was applied to detect miR-122-5p and miR-140-5p in ICH patients and healthy subjects, and the results obtained by SERS were consistent with the results from quantitative real-time polymerase chain reaction, revealing the accuracy of the method. This simple, rapid approach offers great potential for the simultaneous detection of miRNAs in practical clinical applications.
研究领域:
医学诊断
·
生物传感
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）