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choroid plexus CCL2‒CCR2 signaling orchestrates macrophage recruitment and cerebrospinal fluid hypersecretion in hydrocephalus

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Acta Pharmaceutica Sinica B 2024年第10期14卷 4544-4559页

作者： Qiguang Wang Fei Liu Yue Li Huan Zhang Xin Qi Ke Wu Yi Zhang Shenglan You Wenke Liu Xuhui Hui Hanmei Li Lei Zhu Huile Gao Jian Cheng Department of Neurosurgery West China HospitalSichuan UniversityChengdu 610041China Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041China Institute of Thoracic Oncology West China HospitalSichuan UniversityChengdu 610041China Institutes for Systems Genetics Frontiers Science Center for Disease-Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China Institute of Rare Diseases West China Hospital of Sichuan UniversityChengdu 610041China Research Core Facility of West China Hospital Sichuan UniversityChengdu 610041China Key Laboratory of Coarse Cereal Processing School of Food and Biological EngineeringChengdu UniversityChengdu 610106China

The choroid plexus(ChP)serves as the principal origin of cerebrospinal fluid(CSF).CSF hypersecretion due to ChP inflammation has emerged as an important pathogenesis of hydrocephalus ***,the precise mechanisms of ChP inflammation and the ensuing CSF hypersecretion in hydrocephalus remain *** the present study,we elucidate the critical role of macrophages in the pathogenesis of ChP ***,we identify the chemokine CCL2,released by ChP epithelial cells,recruits CCR2+monocytes to the ChP thereby inciting hydrocephalus *** accumulated ChP macrophages increase the inflammation in ChP epithelial cells through TNF-α/TNFR1/NF-κB signaling cascade,thereby leading to CSF ***,augmentation of ChP‒CCL2 using an adeno-associated viral approach(AAV)exacerbates macrophage recruitment,activation,and ventriculomegaly in rat PHH *** application of Bindarit,a specific CCL2 inhibitor,significantly inhibits ChP macrophage infiltration and activation and reduces CSF secretion ***,the administration of CCR2 antagonist(INCB 3284)reduces ChP macrophage accumulation and *** study not only unveils the ChP CCL2‒CCR2 signaling in the pathophysiology of hydrocephalus but also unveils Bindarit as a promising therapeutic choice for the management of posthemorrhagic hydrocephalus.

关键词： Hydrocephalus Macrophages CCL2 CCR2 choroid plexus Epithelial cells Crosstalk Cerebrospinal fluid hypersecretion

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choroid plexus trophic factors in the developing and adult brain

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Frontiers in Biology 2016年第3期11卷 214-221页

作者： Karen Amaud Ariel A. Di Nardo Center for Interdisciplinary Research in Biology (CIRB) CNRS UMR 7241/INSERM U1050 Labex Memolife CollOge de France 75231 Paris France Universite Pierre et Marie Curie Paris VI Paris France

The choroid plexus （CP）, localized in brain ventricles, is the major source of cerebrospinal fluid （CSF） and participates in the blood-CSF barrier. It is essential for brain immunosurveillance and the clearance of toxics, and for brain development and activity. Indeed, the CP secretes a large variety of trophic factors in the CSF that impact the entire brain. These factors are mainly implicated in neurogenesis, but also in the maintenance of brain functions and the vasculature. In this mini-review, we provide an overview of the various trophic factors secreted by the CP in the CSF, and describe their roles in the developing, adult and diseased brain.

关键词： choroid plexus trophic factors CSF neurogenesis development adult brain

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High Blood Pressure Effects on the Brain Barriers and choroid plexus Secretion

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Neuroscience & Medicine 2012年第1期3卷 60-64页

作者： Ibrahim González-Marrero Leandro Castaneyra-Ruiz Juan M.González-Toledo Agustín Castaneyra-Ruiz Héctor de Paz-Carmona Lidia Ruiz-Mayor Agustín Castaneyra-Perdomo Emilia M.Carmona-Calero Departamento de Anatomía Facultad de MedicinaUniversidad de La LagunaTenerifeSpain Departamento de Biotecnología Instituto de Investigación y Ciencias de Puerto del RosarioFuerteventuraSpain

High blood pressure produces ventricular dilation, variations in circumventricular organs and changes in the cerebrospinal fluid compositions. On the other hand, chronic hypertension in spontaneously hypertensive rats can cause changes in the integrity of the brain barriers: blood-cerebrospinal fluid barrier and blood brain barrier. The permeability of the brain barriers can be studied by using transthyretin and S-100β. In the present work we study the integrity of the brain barrier and the choroid plexus function variations in arterial hypertension. Control rats and spontaneously hypertensive rats were used and the choroid plexus were processed by immunohistochemistry with anti-transthyretin and anti-vasopressin. Western blot was also performed in cerebrospinal fluid, serum and choroid plexus using anti-S-100β, anti-transthyretin. The accumulation of transthyretin immunoreactive was bigger in spontaneously hypertensive rats with respect to the control. Vasopressin was also higher in spontaneously hypertensive rats with respect to the control. Western blot showed that transthyretin tetramer was higher in the spontaneously hypertensive rats than in the control rats. The expression of transthyretin monomer was lower in hypertensive rats than the control in the cerebrospinal fluid, the transthyretin monomer reaction in the blood was stronger in hypertensive than in control rats. Western blot for the S-100 β showed an increase in blood and cerebrospinal fluid of hypertensive rats. The high blood pressure produces a disruption of the blood brain barrier and blood to cerebrospinal fluid barrier that allows extravasations from the cerebrospinal fluid to the blood and from the blood to the cerebrospinal fluid.

关键词： Brain Barriers choroid plexus Arterial Hypertension

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Effect of Lycopene on Inflammatory Response and TLR4 Pathway of choroid plexus in β-amyloid Induced Model of Alzheimer's Disease

Effect of Lycopene on Inflammatory Response and TLR4 Pathway...

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中国营养学会第十次特殊营养学术会议

作者： LIU Chong-bin JI Tao WANG Li-qun YI Yan-feng WANG Rui GAO Xi-ren Department of Physiology Basic Medical Science Building Huzhou Normal College

Objective: The present study was designed to investigate the neuroprotective potential of lycopene on inflammatory response and TLR4 pathway of choroid plexus inβ-amyloid induced model of Alzheimer’s disease. Methods: 40 adult SD rats(Body weight:250±18.7 g) were randomly divided into five groups(n= 8): control, AD model, AD+lycopene(ig.5 mg/kg.d), AD+lycopene(ig. 10 mg/kg.d) and lycopene group. The rats were adapted for one week prior to the present experiment. 8μgβ-amyloid(Aβ) was administered through intracerebroventricular(ICV) by using stereotaxic instrument in AD group and the AD+lycopene group rats’ bilateral hippocampus, and the control and lycopene groups with equal saline. All the rats were trained on a Morris water maze test after 2, 3, 4, 5 weeks to identify leaming and memory ability of the rats. The rats were sacrificed and the blood were prepared for the quantification of TNF-α, IL-1β and IL-6β level by ELISA. The expression of TLR4, NF-κB p65 m RNA and protein was detected by RT-q PCR and western blot. Western blot was also used to detect the expression of PS-1 and β-APP in hippocampus. Results: Compared with the control group, the latent period of escape and activity time in AD group was significantly longer(P< 0.05).But the rats performed better in AD+lycopene groups than in AD group(P< 0.05). Compared with the control group, the level of TNF-α, IL-1β and IL-6β in AD group was significantly incresed(P<0.05), but significantly decresed in AD+lycopene groups(P< 0.05). Compared with the control group, the expression of TLR4, NF-κB p65 mRNA and protein were also significantly incresed(P< 0.05), but significantly decresed in AD+lycopene groups(P< 0.05). Along with this,compared with the control group, the expression of PS-1 and β-APP in hippocampus were significantly incresed(P< 0.05), but were reversed on lycopene treatment(P< 0.05). Conclusion:Collectively, these observations provide an evidence for beneficial effect of lycopene supplementation in β-a

关键词： Lycopene choroid plexus Alzheimer’s Disease Inflammatory response

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The brain as a source and a target of prolactin in mammals

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Neural Regeneration Research 2022年第8期17卷 1695-1702页

作者： Ana R.Costa-Brito Isabel Gonçalves Cecília R.A.Santos CICS-UBI-Health Sciences Research Centre Universidade da Beira InteriorCovilhãPortugal C4-UBI-Cloud Computing Competence Centre Universidade da Beira InteriorCovilhãPortugal

Prolactin is a polypeptide hormone associated with an extensive variety of biological *** the roles of prolactin in vertebrates,some were preserved throughout *** is the case of its function in the brain,where prolactin receptors,are expressed in different structures of the central nervous *** the brain,prolactin actions are principally associated with reproduction and parental behavior,and involves the modulation of adult neurogenesis,neuroprotection,and neuroplasticity,especially during pregnancy,thereby preparing the brain to *** is mainly produced by specialized cells in the anterior pituitary ***,during vertebrate evolution many other extrapituitary tissues do also produce prolactin,like the immune system,endothelial cells,reproductive structures and in several regions of the *** review summarizes the relevance of prolactin for brain function,the sources of prolactin in the central nervous system,as well as its local production and secretion.A highlight on the impact of prolactin in human neurological diseases is also provided.

关键词： brain brain disease choroid plexus neurogenesis neuroplasticity neuroprotection prolactin prolactin receptor

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Mechanism of Cu entry into the brain:many unanswered questions

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Neural Regeneration Research 2024年第11期19卷 2421-2429页

作者： Shubhrajit Roy Svetlana Lutsenko Department of Physiology Johns Hopkins University School of MedicineBaltimoreMDUSA

Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical *** requirements for Cu in the brain vary depending on specific brain regions,cell types,organism age,and nutritional *** imbalances cause or contribute to several life-threatening neurologic disorders including Menkes disease,Wilson disease,Alzheimer’s disease,Parkinson’s disease,and *** the well-established role of Cu homeostasis in brain development and function,the mechanisms that govern Cu delivery to the brain are not well *** review summarizes available information on Cu transfer through the brain barriers and discusses issues that require further research.

关键词： ATOX1 ATP7A ATP7B blood-brain barrier brain choroid plexus copper SLC31A1

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Danshen-Chuanxiongqin Injection attenuates cerebral ischemic stroke by inhibiting neuroinflammation via the TLR2/ TLR4-MyD88-NF-κB Pathway in tMCAO mice

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Chinese Journal of Natural Medicines 2021年第10期19卷 772-783页

作者： XU Xiao-Jing LONG Jin-Bo JIN Kai-Yu CHEN Li-Bing LU Xiao-Yan FAN Xiao-Hui Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China State Key Laboratory of Component-Based Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China

Danshen-Chuanxiongqin Injection(DCI)is a commonly used traditional Chinese medicine for the treatment of cerebral ischemic stroke in ***,its underlying mechanisms remain completely *** current study was designed to explore the protective mechanisms of DCI against cerebral ischemic stroke through integrating whole-transcriptome sequencing coupled with network pharmacology ***,using a mouse model of cerebral ischemic stroke by transient middle cerebral artery occlusion(tMCAO),we found that DCI(4.10 mL·kg−1)significantly alleviated cerebral ischemic infarction,neurological deficits,and the pathological injury of hippocampal and cortical neurons in ***,the whole-transcriptome sequencing was performed on brain *** cerebral ischemia disease(CID)network was constructed by integrating transcriptome sequencing data and cerebrovascular disease-related *** results showed CID network was imbalanced due to tMCAO,but a recovery regulation was observed after DCI *** analysis of the key genes with recovery efficiency showed that the neuroinflammation signaling pathway was highly enriched,while the TLR2/TLR4-MyD88-NF-κB pathway was predicted to be ***,the in vivo validation experiments confirmed that DCI exhibited protective effects against cerebral ischemic stroke by inhibiting neuroinflammation via the TLR2/TLR4-MyD88-NF-κB *** interestingly,DCI markedly suppressed the neutrophils infiltrated into the brain parenchyma via the choroid plexus route and showed anti-neuroinflammation *** conclusion,our results provide dependable evidence that inhibiting neuroinflammation via the TLR2/TLR4-MyD88-NF-κB pathway is the main mechanism of DCI against cerebral ischemic stroke in mice.

关键词： Danshen-Chuanxiongqin Injection Cerebral ischemic stroke Network pharmacology Neuroinflammation Neutrophil choroid plexus

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In situ staining of the primo vascular system in the ventricles and subarachnoid space of the brain by trypan blue injection into the lateral ventricle

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Neural Regeneration Research 2011年第28期6卷 2171-2175页

作者： Jingxing Dai Byung-Cheon Lee Ping An Zhendong Su Rongmei Qu Ki Hoon Eom Kwang-Sup Soh Department of Human Anatomy Southern Medical University Guangzhou 510515 Guangdong Province China Nano Primo Research Center Advanced Institute of Convergence Technology Seoul National University Seou1443-270 Korea Pharmacupuncture Medical Research Institute Korean Pharmacupuncture Institute Seoul Korea

We examined a new method for visualization of the primo vascular system in the rat brain involving lateral ventricle injection of trypan blue. Results showed that the primo vascular system in the lateral ventricles and arachnoid mater of the brain were preferentially stained relative to blood vessels and fascia. The primo-vessels along blood vessels in the brain were clearly exhibited. In addition, the primo vascular system was evident between the fourth ventricle and the quadrigeminal cistern. Our experimental findings indicate that this new technique of lateral ventricle injection of trypan blue can visualize the primo vascular system in lateral ventricles and arachnoid mater of rats in situ.

关键词： trypan blue primo vascular system fascia cerebral ventricles choroid plexus neuroanatomy neural regeneration

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Regulation of Phosphorylated Protein PHB1 on Z310 Cell Cycle Arrest Induced by Manganese Chloride

Regulation of Phosphorylated Protein PHB1 on Z310 Cell Cycle...

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2019年海峡两岸暨港澳青年科学家毒理学学术交流会

作者： Haiming Jing Jiandong Wang Zinan Li Zhuangsheng Tan Hong Hu Junyu Ning Guojun Li Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning Beijing Center for Disease Prevention and Control/Beijing Center of Preventive Medicine Research

The pathological injury of brain parenchyma caused by chronic maganism is ***,the early diagnosis and treatment of chronic maganism are still difficult to *** neurons are the final target of manganese induced ***,we found that manganese chloride（MnCl2） induces pathological injury of choroid plexus,which constitute blood-CSF barrier in the ventricles,secrete cerebrospinal fluid and synthesize dopamine neuron specific trophic factor（GDF-15）.In addition,our previous study also indicated that manganese induced the cell cycle arrest of Z310 choroidal epithelial cells,which may be associated with the up-regulated protein prohibin 1（PHB1）.At present,the effects of manganese on the two proteins in peripheral blood circulation and central nervous system choroid plexus has not been *** has still unknown about the mechanism of regulation of PHB1 on Z310 Cell Cycle Arrest induced by manganese ***,in our study,by enzyme linked immunosorbent assay（ELISA） we measured the content of PHB1 and GDF-15 in serum and cerebrospinal fluid of male workers with occupational manganese exposure and chronic manganese poisoning,and the content of GDF-15 in Z310 cells treated with MnCl2 and the culture supernatant,the level of basic expression of PHB1 and GDF-15 in vivo and the effects of manganese chloride on them were *** addition,by gene point mutation and transfection technique we established PHB1 Y114 F mutant cells and PHB1 T258 A mutant cells（258 Thr dephosphorylated cells,PHB1 T258 A dephosphorylated cells） to study regulation of phosphorylated protein PHB1 on Z310 Cell Cycle Arrest induced by *** results showed that the basal expression of GDF-15 and PHB1 were detected in human serum,rat cerebrospinal fluid and serum,as well as in Z310 *** exposure of manganese,the serum GDF-15 and PHB1 contents of male welders were higher than those of the control *** experimental study in vitro

关键词： manganese chloride(MnCl2) prohibin 1(PHB1) choroid plexus cell cycle arrest

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Regulation of phosphorylated protein PHB1 on Z310 cell cycle arrest induced by manganese chloride

Regulation of phosphorylated protein PHB1 on Z310 cell cycle...

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中国毒理学会第九次全国毒理学大会

作者： JING Hai-ming WANG Jian-dong LI Zi-nan TAN Zhuang-sheng HU Hong NING Jun-yu LI Guo-jun Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning Beijing Center for Disease Prevention and ControlBeijing Center of Preventive Medicine Research

The pathological injury of brain parenchyma caused by chronic maganism is ***, the early diagnosis and treatment of chronic maganism are still difficult to achieve. Dopaminegic neurons are the final target of manganese induced neurotoxicity. Previously, we found that manganese chloride(MnCl) induces pathological injury of choroid plexus, which constitute blood-CSF barrier in the ventricles, secrete cerebrospinal fluid and synthesize dopamine neuron specific trophic factor(GDF-15). In addition, our previous study also indicated that manganese induced the cell cycle arrest of Z310 choroidal epithelial cells, which may be associated with the up-regulated protein prohibin1(PHB1). At present, the effects of manganese on the two proteins in peripheral blood circulation and central nervous system choroid plexus has not been reported. It has still unknown about the mechanism of regulation of PHB1 on Z310 Cell Cycle Arrest induced by manganese yet. Therefore, in our study, by enzyme linked immunosorbent assay(ELISA) we measured the content of PHB1 and GDF-15 in serum and cerebrospinal fluid of male workers with occupational manganese exposure and chronic manganese poisoning, and the content of GDF-15 in Z310 cells treated with MnCl2 and the culture supernatant, the level of basic expression of PHB1 and GDF-15 in vivo and the effects of manganese chloride on them were investigated. In addition, by gene point mutation and transfection technique we established PHB1 Y114 F mutant cells and PHB1 T258 A mutant cells(258 Thr dephosphorylated cells,PHB1 T258 A dephosphorylated cells) to study regulation of phosphorylated protein PHB1 on Z310 Cell Cycle Arrest induced by manganese. The results showed that the basal expression of GDF-15 and PHB1 were detected in human serum, rat cerebrospinal fluid and serum, as well as in Z310 cells. After exposure of manganese, the serum GDF-15 and PHB1 contents of male welders were higher than those of the control group. The exper

关键词： manganese chloride(MnCl2) prohibin 1(PHB1) choroid plexus cell cycle arrest

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