GENE EXPRESSION PATTERNS
·
2022
·
IF 1.488
Jian Zhou,Yan-Jing Yang,Rui-Hai Gan,Yang Wang,Zhi Li,Xiao-Juan Zhang,Jian-Fang Gui,Li Zhou
Foxl2 plays conserved central function in ovarian differentiation and maintenance in several fish species. However, its expression pattern and function in fish embryogenesis are still largely unknown. In this study, we first presented a sequential expression pattern of zebrafish foxl2a and foxl2b during embryo development. They were predominantly expressed in the cranial paraxial mesoderm (CPM) and cranial venous vasculature (CVV) during somitogenesis and subsequently expressed in the pharyngeal arches after 48 h post-fertilization (hpf). Then, we compared the brain structures among zebrafish wildtype (WT) and three homozygous foxl2 mutants ( foxl2a −/− , foxl2b −/− and foxl2a −/− ; foxl2b −/− ) and found the reduction of the fourth ventricle in the three foxl2 mutants, especially in foxl2a −/− ; foxl2b −/− mutant. Finally, we detected several key transcription factors involved in the gene regulatory network of midbrain-hindbrain boundary (MHB) patterning, such as wnt1 , en1b and pax2a . Their expression levels were obviously downregulated in MHB of foxl2a −/− and foxl2a −/− ; foxl2b −/− mutants. Thus, we suggest that Foxl2a and Foxl2b are involved in MHB and the fourth ventricle development in zebrafish. The current study provides insights into the molecular mechanism underlying development of brain ventricular system.
研究领域:
发育生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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
PATHOLOGY RESEARCH AND PRACTICE
·
2024
·
IF 2.9
Haiping Zhang,Wei Li
Background Intracerebral hemorrhage (ICH) is one deadly subtype of stroke with high morbidity and mortality. Oxidative stress and inflammation are major factors contributing to blood-brain barrier (BBB) dysfunction, which induces perihematoma edema and exacerbates ICH-induced secondary brain injury. SYN1 is a crucial neuronal phosphoprotein that plays a pivotal role in neuronal development. Our study was devised to clarify the function of SYN1 in hemin-induced cell injury in PC12 cells and brain injury in ICH rat models. Methods For in vitro assay, PC12 cells were first stimulated by 150 µM hemin for 4 h and then transfected with si-SYN1 and pcDNA3.1-SP1. Cell viability was tested through lactate dehydrogenase (LDH) release and CCK-8 assays. Cell apoptosis was observed through TUNEL staining. Inflammatory factors (IL-1β, IL-6, and TNF-α) were evaluated through western blotting. Oxidative markers (GSH, MDA, and SOD) were detected by adopting commercial kits. The binding sites of SP1 on the SYN1 promoter were predicted by using the JASPAR database and were validated through performing CHIP and luciferase reporter assays. SP1 and SYN1 expression in PC12 cells was investigated by RT-qPCR. For in vivo assay, rats were administrated intracerebroventricularly with si-SYN1 at 72 h before ICH induction. SYN1 and SP1 expression in ICH rats was assessed by RT-qPCR. Neurological deficits, brain edema, and BBB disruption at 24 h following ICH were assessed by conducting neurobehavioral tests, brain water content examination, and Evans blue extravasation assay. Results In vitro, hemin stimulation elevated SYN1 expression, attenuated cell viability, enhanced apoptosis, and induced inflammation and oxidative stress in PC12 cells, which were offset by SYN1 knockdown. SP1 bound to the SYN1 promoter region and positively regulated SYN1 expression. Overexpressing SP1 antagonized the impacts of SYN1 downregulation on hemin-induced damage in PC12 cells. In vivo , SYN1 and SP1 expression was upregulated in ICH rat models. Administration of si-SYN1 effectually improved neurological function, attenuated brain edema, and ameliorated BBB disruption following ICH. Conclusion SP1-mediated SYN1 probably participates in the process of neuronal damage, BBB disruption, and brain injury following ICH.
研究领域:
神经科学
·
细胞生物学
·
分子生物学
·
病理生理学
✓ 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
IEEE SENSORS JOURNAL
·
2024
·
IF 4.3
Penghai Li,Fengzhou Li,Kun Wang
The brain serves as the central hub for both our physiological and psychological activities, and current research on the human brain mostly relies on electroencephalography (EEG) method. Hence, we have developed a flexible nanozymes/iridium-titanium dioxide (SAN/Ir-TiO
2
) dry electrode for collecting EEG signals. Due to the hygroscopic nature of SAN nanozymes, they facilitate the maintenance of skin moisture balance. Additionally, the combination of iridium nanoparticles with a titanium dioxide nanotube array enables rapid electron transfer, resulting in an average impedance of 14.2 kΩ in the no-hair region and 19.9 kΩ in the hair region for the electrode. Moreover, in experiments involving blinking, clenching teeth, and alpha wave blocking, signal collection correlation between SAN (single atom nanozymes)/Ir-TiO
2
and traditional Ag/AgCl electrodes is 97.1% to 99.5%, and the signal collection correlation between electrodes from the market and traditional Ag/AgCl electrodes is 95.5% to 99.2%. In Steady-State Visual Evoked Potential (SSVEP) experiments with a 9-channel cap, stimulation frequencies ranging from 7.5Hz to 14Hz were recorded and subjected to frequency domain analysis. Within the range of 7.5Hz to 14Hz, the signal-to-noise ratio ranged from 7.5 to 14.1db, surpassing the performance in other regions. In an 8-command SSVEP classification experiment, the train accuracy and online accuracy were as high as 92.8% and 92.8% respectively, demonstrating the feasibility of using SAN/Ir-TiO
2
dry electrodes for Brain-Computer Interface (BCI) technology.
研究领域:
生物医学工程
·
神经科学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Qian Li,Ziyan Tang,Yuanyuan Zhang,Tianyu Yuan,Bochuan Yuan,Lina Du,Yiguang Jin
Brain-targeted drug delivery has been a research hotspot, and substantial amount of related studies were already translated into standard therapy and put into clinical use. However, low effective rate retains a huge challenge for brain disease. Because, the blood–brain barrier (BBB) protects brain from pathogenic molecules and tightly controls the process of molecular transportation, which gives rise to poor-liposoluble drugs or molecules with high molecular weight cannot permeate the barrier to exert treating effect. There is an ongoing process to dig out more methods for efficient brain-targeted drug delivery. Besides modified chemical methods such as prodrugs design and brain-targeted nanotechnology, physical methods as a novel initiative could enhance the treatment effect for brain disease. In our study, the influence of low-intensity ultrasound on transient opening BBB and the related applications were explored. A medical ultrasound therapeutic device (1 MHz) was used on heads of mice at different intensities and for different treating time. Evans blue was used as a model to exhibit the permeability of the BBB after subcutaneous injection . Three types of intensities (0.6, 0.8, and 1.0 W/cm 2 ) and duration times (1, 3, and 5 min) of ultrasound were respectively investigated. It was found that the combinations of 0.6 W/cm 2 /1 min, 0.6 W/cm 2 /3 min, 0.6 W/cm 2 /5 min, 0.8 W/cm 2 /1 min, and 1.0 W/cm 2 /1 min could open the BBB sufficiently with significant Evans blue staining in the brain. Brain pathological analysis showed structural change on moderate degree was found on cerebral cortex after ultrasound and could recovered rapidly. There are no obvious changes in the behavior of mice after ultrasound processing. More importantly, the BBB recovered quickly at 12 h after ultrasound application with complete BBB structure and unbroken tight junction, suggesting that ultrasound was safe to apply for brain-targeted drug delivery. Proper use of local ultrasound on the brain is a promising technique to open the BBB and enhance brain-targeted delivery.
研究领域:
神经科学
·
药理学
·
治疗技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Zhongyi Ma,Xinlong Liu,Xinyu Xie,Yike Fang,Dingxi Jiang,Chen Zhao,Pingrong Li,Yu Fu,Lianghong Ye,Yuan Gao,Shuang Wu,Chong Li
Overcoming the challenges associated with brain-targeted drug delivery involves addressing both the limited biodistribution of drugs and microcirculation issues that hinder their accumulation in brain lesions. In this study, we propose a comprehensive strategy leveraging vinpocetine, a compound known to enhance cerebral blood flow (CBF), to improve drug delivery to the brain. Initially, the pre-administration of vinpocetine in the form of a microemulsion significantly enhances nanomedicine uptake into the brain by selectively boosting CBF. This creates a more favorable environment for drug distribution while also mitigating chemotherapy-induced cerebrovascular accidents. Building upon this, the use of vinpocetine as a targeting ligand for liposomes or lipid nanoparticles, compared to typical brain-targeting ligands (GSH, Apamin, and Angiopep-2), not only significantly improves drug distribution in the brain but also selectively targets glioma regions and maintains excellent immunocompatibility. Expanding on these findings, the direct conjugation of vinpocetine with therapeutic compounds leads to superior brain accumulation and enhanced antitumor efficacy, thereby extending its therapeutic potential. These results highlight the broad applicability of vinpocetine-based strategies for achieving efficient and precise brain-targeted drug delivery, offering promising prospects for treating a range of central nervous system disorders.
研究领域:
药理学
·
神经科学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2020
·Vol. 26
·期 12
·1288-1302
·
IF 4.074
Meng Gao,Weitian Lu,Yue Shu,Zhengyu Yang,Shanquan Sun,Jin Xu,Shengwei Gan,Shujuan Zhu,Guoping Qiu,Fei Zhuo,Shiye Xu,Yiying Wang,Junhong Chen,Xuan Wu,Juan Huang
Background Specific highly polarized aquaporin-4 (AQP4) expression is reported to play a crucial role in blood-brain barrier (BBB) integrity and brain water transport balance. The upregulation of polymerase δ-interacting protein 2 (Poldip2) was involved in aggravating BBB disruption following ischemic stroke. This study aimed to investigate whether Poldip2-mediated BBB disruption and cerebral edema formation in mouse bacterial meningitis (BM) model occur via induction of AQP4 polarity loss. Methods and Results Mouse BM model was induced by injecting mice with group B hemolytic streptococci via posterior cistern. Recombinant human Poldip2 (rh-Poldip2) was administered intranasally at 1 hour after BM induction. Small interfering ribonucleic acid (siRNA) targeting Poldip2 was administered by intracerebroventricular (i.c.v) injection at 48 hours before BM induction. A specific inhibitor of matrix metalloproteinases (MMPs), UK383367, was administered intravenously at 0.5 hour before BM induction. Western blotting, immunofluorescence staining, quantitative real-time PCR, neurobehavioral test, brain water content test, Evans blue (EB) permeability assay, transmission electron microscopy (TEM), and gelatin zymography were carried out. The results showed that Poldip2 was upregulated and AQP4 polarity was lost in mouse BM model. Both Poldip2 siRNA and UK383367 improved neurobehavioral outcomes, alleviated brain edema, preserved the integrity of BBB, and relieved the loss of AQP4 polarity in BM model. Rh-Poldip2 upregulated the expression of MMPs and glial fibrillary acidic protein (GFAP) and downregulated the expression of β-dystroglycan (β-DG), zonula occludens-1 (ZO-1), occludin, and claudin-5; whereas Poldip2 siRNA downregulated the expression of MMPs and GFAP, and upregulated β-DG, ZO-1, occludin, and claudin-5. Similarly, UK383367 downregulated the expression of GFAP and upregulated the expression of β-DG, ZO-1, occludin, and claudin-5. Conclusion Poldip2 inhibition alleviated brain edema and preserved the integrity of BBB partially by relieving the loss of AQP4 polarity via MMPs/β-DG pathway.
研究领域:
神经科学
·
药理学
·
分子生物学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL NEUROLOGY
·
2024
·
IF 4.6
Jing Qiu,Yi-Han Wang,Xiu-Ming Wang,Hui-Sheng Chen
The pericytes (PCs) surrounding capillaries are vital regulators of capillary constriction. Persistent PC contraction results in the increased capillary constriction, therefore leading to the impaired cerebral blood flow (CBF) recovery after reperfusion and worsening the clinical outcomes in stroke patients. However, the potential determinants of PC functions during ischemia/reperfusion are poorly understood. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit Delta (PIK3CD/PI3Kδ) is a crucial factor involved with neuronflammation during ischemic stroke. PI3Kδ has shown the expression in PCs, while its effect on PC functions has not been explored yet. In this study, a rodent ischemia/reperfusion model was established in C57BL/6 mice via transient middle cerebral artery occlusion and reperfusion (MCAO/R). The PI3Kδ expression in ischemic penumbra was remarkably upregulated following MCAO/R induction. PI3Kδ inhibitor CAL-101 improved the CBF recovery, ischemic brain injury, and suppressed capillary constriction in MCAO/R mice. Besides, the production of tumor necrosis factor alpha (TNF-α), an inducer for tissue injury, and the expression of transient receptor potential vanilloid type 2 (TRPV2), a channel protein permitting calcium (Ca 2+ ) uptake, were significantly reduced in ischemic penumbra after CAL-101 treatment. In vitro, oxygen-glucose deprivation and reoxygenation (OGD/R) enhanced the expression of PI3Kδ and TRPV2 in primary mouse PCs. CAL-101 suppressed the TNF-α-induced TRPV2 expression in OGD/R-treated PCs, thus inhibiting the Ca 2+ uptake and PC contraction. Collectively, this study suggests that PI3Kδ is a critical regulator of PC function during ischemic stroke.
研究领域:
神经科学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Stroke & Cerebrovascular Diseases
·
2021
·
IF 2.136
Yue Shu,Juan Huang,Meng Gao,Shengwei Gan,Shujuan Zhu,Shiye Xu,Zhengyu Yang,Yuhui Liao,Weitian Lu
Dentin matrix protein 1 (DMP1) is an extracellular matrix phosphoprotein that is known to facilitate mineralization of collagen in bone and promote osteoblast/odontoblast differentiation. Blood-brain barrier (BBB) disruption is the major pathogenesis in secondary brain injury after intracerebral hemorrhage (ICH). This study aimed to investigate the expression pattern of DMP1 in the mouse brain and explore the role of DMP1 in BBB disruption and brain injury in a mouse model of ICH. Mice were subjected to autologous blood injection-induced ICH. Immunofluorescence staining, western blot analysis , neurobehavioral tests, brain water content measurements, Evans blue permeability assay, and transmission electron microscopy were performed. Small interfering RNA targeting DMP1 (DMP1 siRNA) was administered at 72 h prior to ICH. Results showed that DMP1 is expressed extensively in the mouse brain, and is upregulated in the ICH model. Administration of DMP1 siRNA effectively ameliorated BBB disruption, attenuated brain edema , and improved neurological function after ICH. Moreover, the expression of zonula occludens-1 (ZO-1) and occludin were upregulated, and matrix metalloproteinase-9 (MMP-9) was downregulated in the ICH model. DMP1 siRNA administration reversed the expression of ZO-1, occludin, and MMP-9. These results demonstrated that DMP1 upregulation plays an essential role in inducing BBB disruption and brain injury after ICH. The inhibition of DMP1 could be a potential therapeutic strategy for ICH treatment .
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
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 10
·4723
·
IF 4.9
Jiao Feng,Chengyong Wen,Xiao Zhang,Xiaolong Zhu,Mengmeng Ma,Xiaohong Zhao,Xinbing Sui
Temozolomide (TMZ) remains the frontline chemotherapy for gliomas; yet its clinical efficacy is significantly compromised by inherent instability and the emergence of resistance mechanisms. To surmount these challenges, we engineered a squalenoylated TMZ nanoparticle (SQ-TMZ NPs) via conjugation of TMZ with squalene, enabling enhanced drug stability and improved therapeutic potency against glioblastoma cells. The resulting SQ-TMZ NPs exhibited a precisely controlled nanoscale architecture (~126 nm), demonstrating exceptional stability under physiological and storage conditions, with minimal hemolytic toxicity (<5%). Notably, these nanoparticles conferred superior cytotoxicity in TMZ-resistant glioblastoma T98G cells, attributed to the amplification of intracellular reactive oxygen species (ROS) and DNA damage, along with MGMT (O-6-methylguanine-DNA methyltransferase) expression suppression. Furthermore, in vivo imaging confirmed their efficient blood–brain barrier (BBB) penetration and selective tumor accumulation. This study presents a transformative approach by integrating prodrug self-assembly with targeted drug delivery to not only enhance TMZ stability but also decisively reverse glioblastoma resistance, offering a compelling therapeutic advancement.
研究领域:
肿瘤学
·
药剂学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
·
2019
·
IF 3.103
Bin Chen,Zhenghong Chen,Mingjian Liu,Xiaorong Gao,Yijun Cheng,Yongxu Wei,Zhebao Wu,Derong Cui,Hanbing Shang
Intracerebral hemorrhage (ICH) is a devastating subtype of stroke because it has few viable therapeutic options to intervene against primary or second brain injury. Recently, evidence has suggested that ferroptosis, a nonapoptotic form of cell death, is involved in ICH. In this study, we examined whether ICH-induced neuron death is partly ferroptotic in humans and assessed its temporal and spatial characteristics in mice. Furthermore, the ferroptosis inhibitor ferrostatin-1 (Fer-1) was used to examine the role of ferroptosis after ICH. Fold changes in ferroptosis-related gene expression, intracellular iron levels, malondialdehyde (MDA) levels, and both protein levels and cellular localization of cyclooxygenase-2 (COX-2) were measured to monitor ferroptosis. Transmission electron microscopy (TEM) was also performed to examine the ultrastructure of cells after ICH. We found that the expression level of prostaglandin-endoperoxide synthase (PTGS2) was increased in both in vitro and in vivo ICH models; by comparison, expression level of RPL8 was increased in human brain tissue. In mice, iron and MDA levels were significantly increased 3 h after ICH; COX-2 levels were increased at 12 h after ICH and peaked at 3 days after ICH; COX-2 colocalized with NeuN (a neuronal biomarker); and TEM showed that shrunken mitochondria were found at 3 h, 3 days, and 7 days after ICH. Moreover, ICH-induced neurological deficits, memory impairment and brain atrophy were reduced by Fer-1 treatment. Our results demonstrated that neuronal ferroptosis occurs during the acute phase of ICH in brain areas distant from the hematoma and that inhibition of ferroptosis by Fer-1 exerted a long-term cerebroprotective effect.
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
危险品化学品经营许可证（带存储）