Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell...Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell proliferation and differentiation,thereby exerting neuroprotective effects.However,the beneficial effects of endogenous VEGFA/b FGF are limited as their expression is only transiently increased.In this study,we generated multilayered nanofiber membranes loaded with VEGFA/b FGF using layer-by-layer self-assembly and electrospinning techniques.We found that a membrane containing 10 layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1 month.This 10-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation,inhibited neuronal apoptosis,upregulated the expression of tight junction proteins,and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose deprivation.Furthermore,this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3(JAK2/STAT3),Bax/Bcl-2,and cleaved caspase-3.Therefore,this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.展开更多
Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)i...Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities,and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases.In the current research,the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model.Our results revealed that FTY-720 markedly decreased infarct volume,promoted neurological function recovery,and weakened the blood-brain barrier permeability of ischemic rats.The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels.These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.展开更多
An emerging concept termed the neurovascular unit(NVU)underlines neurovascular coupling.It has been reported that NVU impairment can result in neurodegenerative diseases,such as Alzheimer's disease and Parkinson&#...An emerging concept termed the neurovascular unit(NVU)underlines neurovascular coupling.It has been reported that NVU impairment can result in neurodegenerative diseases,such as Alzheimer's disease and Parkinson's disease.Aging is a complex and irreversible process caused by programmed and damage-related factors.Loss of biological functions and increased susceptibility to additional neurodegenerative diseases are major characteristics of aging.In this review,we describe the basics of the NVU and discuss the effect of aging on NVU basics.Furthermore,we summarize the mechanisms that increase NVU susceptibility to neurodegenerative diseases,such as Alzheimer's disease and Parkinson's disease.Finally,we discuss new treatments for neurodegenerative diseases and methods of maintaining an intact NVU that may delay or diminish aging.展开更多
Background:Compatibility is a characteristic of the clinical application of traditional Chinese medicine,often leading to enhanced therapeutic effects.In the treatment of cerebral ischemia,blood-activating and open or...Background:Compatibility is a characteristic of the clinical application of traditional Chinese medicine,often leading to enhanced therapeutic effects.In the treatment of cerebral ischemia,blood-activating and open orifices herbs are frequently used individually;however,their combination is not commonly practiced.This study aims to investigate the impact of combining safflower and borneol as examples of open orifices herbs and blood-activating herbs on the neurovascular unit in rats with ischemic stroke.The objective is to determine whether this combination exhibits superior therapeutic efficacy compared to using borneol or safflower alone while exploring its underlying mechanism.These findings may provide novel insights for clinical treatments.Methods:SD male rats were randomly divided into 6 groups:sham operation group,model group,borneol group(0.1 g/kg),safflower group(5 g/kg),borneol combined with safflower group(0.1 g/kg+5 g/kg)and nimodipine group(0.01 g/kg).The middle cerebral artery cerebral ischemia(MCAO)model were prepared after continuous intragastric administration for 7 days in each group,the neurological function of each group were scored 24h after operation,and water content in brain tissue were measured by weighing method.The activity of superoxide dismutase(SOD)and the contents of nitric oxide(NO)and malondialdehyde(MDA)in brain tissue and serum were determined by spectrophotometry,and the mRNA expressions of matrix metalloproteinase 2(MMP-2),tight junction protein 1(ZO-1),vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF)were detected by Real time PCR.Result:Compared with the model group,the group treated with borneol combined with safflower exhibited a significant decrease in the neural function score of MCAO rats(P<0.01).Additionally,it led to a reduction in brain tissue water content(P<0.01),elevated SOD activity,and reduced levels of NO and MDA in both serum and brain tissue(P<0.01 or P<0.05).Moreover,this treatment resulted in a decrease in the mRNA expression of MMP-2 and an increase in ZO-1 in brain tissue,along with an increase in the mRNA expression of VEGF and BDNF(P<0.01).Conclusion:Borneol combined with safflower demonstrates a protective effect on the neurovascular unit in rats with ischemic stroke.This effect is likely associated with increased SOD activity,reduced MDA and NO content in both serum and brain tissue of MCAO rats,and a decrease in MMP-2 mRNA expression in brain tissue,coupled with an increase in ZO-1,VEGF,and BDNF mRNA expression.These effects were superior to those observed with borneol or safflower administered alone.展开更多
Previous studies have shown that models of depression exhibit structural and functional changes to the neurovascular unit. Thus, we hypothesized that diabetes-related depression might be associated with damage to the ...Previous studies have shown that models of depression exhibit structural and functional changes to the neurovascular unit. Thus, we hypothesized that diabetes-related depression might be associated with damage to the hippocampal neurovascular unit. To test this hypothesis, neurons, astrocytes and endothelial cells were isolated from the brain tissues of rat embryos and newborn rats. Hippocampal neurovascular unit co-cultures were produced using the Transwell chamber co-culture system. A model of diabetes-related depression was generated by adding 150 mM glucose and 200 μM corticosterone to the culture system and compared with the neuron + astrocyte and astrocyte + endothelial cell co-culture systems. Western blot assay was used to measure levels of structural proteins in the hippocampal neurovascular unit co-culture system. Levels of basic fibroblast growth factor, angiogenic factor 1, glial cell line–derived neurotrophic factor, transforming growth factor β1, leukemia inhibitory factor and 5-hydroxytryptamine in the hippocampal neurovascular unit co-culture system were measured by enzyme-linked immunosorbent assay. Flow cytometry and terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick end labeling staining was used to assess neuronal apoptosis in the hippocampal neurovascular unit. The neurovascular unit triple cell co-culture system had better barrier function and higher levels of structural and secretory proteins than the double cell co-culture systems. In comparison, in the model of diabetes-related depression, the neurovascular unit was damaged with decreased barrier function, poor structural integrity and impaired secretory function. Moreover, neuronal apoptosis was markedly increased, and 5-hydroxytryptamine levels were reduced. These results suggest that diabetes-related depression is associated with structural and functional damage to the neurovascular unit. Our findings provide a foundation for further studies on the pathogenesis of diabetes-related depression.展开更多
Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin an...Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression of neurotrophic factors. Therefore, HDCA may have therapeutic potential in the clinical management of ischemic stroke. This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine(approval No. BUCM-3-2016040201-2003) in April 2016.展开更多
Objective:To describe the anatomical characteristics and patterns of neurovascular compression (NVC) in patients suffering trigeminal neuralgia(TN) by 3D high-resolution magnetic resonance imaging(MRI) method and imag...Objective:To describe the anatomical characteristics and patterns of neurovascular compression (NVC) in patients suffering trigeminal neuralgia(TN) by 3D high-resolution magnetic resonance imaging(MRI) method and image fusion technique.Methods:The anatomic structure of trigeminal nerve,brain stem and blood vessel was observed in 100 consecutive TN patients by 3D high resolution MRI(3D SPGR,contrast-enhanced T1 3D MP-RAGE and T2/T1 3D FIESTA). The 3D image sources were fused and visualized using 3D DOCTOR software.Results:One or several NVC sites,which usually appeared 0-9.8 mm away from brain stem,were found on the symptomatic side in 93%of the TN cases.Superior cerebellar artery was involved in 76%(71/93) of these cases.The other vessels including antero-inferior cerebellar artery,vertebral artery, basilar artery and veins also contributed to the occurrence of NVC.The NVC sites were found to be located in the proximal segment in 42%of these cases(39/93) and in the distal segment in 45% (42/93).Nerve dislocation or distortion was observed in 32%(30/93).Conclusions:Various 3D high resolution MRI methods combined with the image fusion technique could provide pathologic anatomic information for the diagnosis and treatment of TN.展开更多
Our previous studies have shown that glutamate and hippocampal neuron apoptosis are key signals and direct factors associated with diabetes-related depression,and structural and functional damage to the hippocampal ne...Our previous studies have shown that glutamate and hippocampal neuron apoptosis are key signals and direct factors associated with diabetes-related depression,and structural and functional damage to the hippocampal neurovascular unit has been associated with diabetesrelated depression.However,the underlying mechanism remains unclear.We hypothesized that diabetes-related depression might be associated with the glutamate(Glu)/metabotropic glutamate receptor2/3(mGluR2/3)/phosphoinositide 3-kinase(PI3K)pathway,activated by glucocorticoid receptors in the hippocampal neurovascular unit.To test this hypothesis,rat hippocampal neurovascular unit models,containing hippocampal neurons,astrocytes,and brain microvascular endothelial cells,were treated with 150 mM glucose and 200μM corticosterone,to induce diabetes-related depression.Our results showed that under conditions of diabetes complicated by depression,hippocampal neurovascular units were damaged,leading to decreased barrier function;elevated Glu levels;upregulated glucocorticoid receptor,vesicular glutamate transporter 3(VGLUT-3),and metabotropic glutamate receptor 2/3(mGluR2/3)expression;downregulated excitatory amino acid transporter 1(EAAT-1)expression;and alteration of the balance of key proteins associated with the extracellular signal-regulated kinase(ERK)/glial cell-derived neurotrophic factor(GDNF)/PI3K signaling pathway.Moreover,the viability of neurons was dramatically reduced in the model of diabetes-related depression,and neuronal apoptosis,and caspase-3 and caspase-9 expression levels,were increased.Our results suggest that the Glu/mGluR2/3/PI3K pathway,induced by glucocorticoid receptor activation in the hippocampal neurovascular unit,may be associated with diabetes-related depression.This study was approved by the Laboratory Animal Ethics Committee of The First Hospital of Hunan University of Chinese Medicine,China(approval No.HN-ZYFY-2019-11-12)on November 12,2019.展开更多
The high metabolic demands of the brain require an efficient vascular system to be coupled with neural activity to supply adequate nutrients and oxygen.This supply is coordinated by the action of neurons,glial and vas...The high metabolic demands of the brain require an efficient vascular system to be coupled with neural activity to supply adequate nutrients and oxygen.This supply is coordinated by the action of neurons,glial and vascular cells,known collectively as the neurovascular unit,which temporally and spatially regulate local cerebral blood flow through a process known as neurovascular coupling.In many neurodegenerative diseases,changes in functions of the neurovascular unit not only impair neurovascular coupling but also permeability of the blood-brain barrier,cerebral blood flow and clearance of waste from the brain.In order to study disease mechanisms,we need improved physiologicallyrelevant human models of the neurovascular unit.Advances towards modeling the cellular complexity of the neurovascular unit in vitro have been made using stem-cell derived organoids and more recently,vascularized organoids,enabling intricate studies of non-cell autonomous processes.Engineering and design innovations in microfluidic devices and tissue engineering are progressing our ability to interrogate the cerebrovasculature.These advanced models are being used to gain a better understanding of neurodegenerative disease processes and potential therapeutics.Continued innovation is required to build more physiologically-relevant models of the neurovascular unit encompassing both the cellular complexity and designed features to interrogate neurovascular unit functionality.展开更多
The blood-spinal cord barrier plays a vital role in recovery after spinal cord injury.The neurovascular unit concept emphasizes the relationship between nerves and vessels in the brain,while the effect of the blood-sp...The blood-spinal cord barrier plays a vital role in recovery after spinal cord injury.The neurovascular unit concept emphasizes the relationship between nerves and vessels in the brain,while the effect of the blood-spinal cord barrier on the neurovascular unit is rarely reported in spinal cord injury studies.Mouse models of spinal cord injury were established by heavy object impact and then immediately injected with plateletderived growth factor(80μg/kg)at the injury site.Our results showed that after platelet-derived growth factor administration,spinal cord injury,neuronal apoptosis,and blood-spinal cord barrier permeability were reduced,excessive astrocyte proliferation and the autophagyrelated apoptosis signaling pathway were inhibited,collagen synthesis was increased,and mouse locomotor function was improved.In vitro,human umbilical vein endothelial cells were established by exposure to 200μM H2O2.At 2 hours prior to injury,in vitro cell models were treated with 5 ng/mL platelet-derived growth factor.Our results showed that expression of blood-spinal cord barrier-related proteins,including Occludin,Claudin 5,andβ-catenin,was significantly decreased and autophagy was significantly reduced.Additionally,the protective effects of platelet-derived growth factor could be reversed by intraperitoneal injection of 80 mg/kg chloroquine,an autophagy inhibitor,for 3 successive days prior to spinal cord injury.Our findings suggest that platelet-derived growth factor can promote endothelial cell repair by regulating autophagy,improve the function of the blood-spinal cord barrier,and promote the recovery of locomotor function post-spinal cord injury.Approval for animal experiments was obtained from the Animal Ethics Committee,Wenzhou Medical University,China(approval No.wydw2018-0043)in July 2018.展开更多
In 2001,the concept of the neurovascular unit was introduced at the Stroke Progress Review Group meeting.The neurovascular unit is an important element of the health and disease status of blood vessels and nerves in t...In 2001,the concept of the neurovascular unit was introduced at the Stroke Progress Review Group meeting.The neurovascular unit is an important element of the health and disease status of blood vessels and nerves in the central nervous system.Since then,the neurovascular unit has attracted increasing interest from research teams,who have contributed greatly to the prevention,treatment,and prognosis of stroke and neurodegenerative diseases.However,additional research is needed to establish an efficient,low-cost,and low-energy in vitro model of the neurovascular unit,as well as enable noninvasive observation of neurovascular units in vivo and in vitro.In this review,we first summarize the composition of neurovascular units,then investigate the efficacy of different types of stem cells and cell culture methods in the construction of neurovascular unit models,and finally assess the progress of imaging methods used to observe neurovascular units in recent years and their positive role in the monitoring and investigation of the mechanisms of a variety of central nervous system diseases.展开更多
Biological studies typically rely on a simple monolayer cell culture,which does not reflect the complex functional characteristics of human tissues and organs,or their real response to external stimuli.Microfluidic te...Biological studies typically rely on a simple monolayer cell culture,which does not reflect the complex functional characteristics of human tissues and organs,or their real response to external stimuli.Microfluidic technology has advantages of high-throughput screening,accurate control of the fluid velocity,low cell consumption,long-term culture,and high integration.By combining the multipotential differentiation of neural stem cells with high throughput and the integrated characteristics of microfluidic technology,an in vitro model of a functionalized neurovascular unit was established using human neural stem cell-derived neurons,astrocytes,oligodendrocytes,and a functional microvascular barrier.The model comprises a multi-layer vertical neural module and vascular module,both of which were connected with a syringe pump.This provides controllable conditions for cell inoculation and nutrient supply,and simultaneously simulates the process of ischemic/hypoxic injury and the process of inflammatory factors in the circulatory system passing through the blood-brain barrier and then acting on the nerve tissue in the brain.The in vitro functionalized neurovascular unit model will be conducive to central nervous system disease research,drug screening,and new drug development.展开更多
Objective: To investigate the significance of intrafascial neurovascular bundle spare technique in radical cystectomy. Methods: Between March 2010 and December 2011, a total of 26 bladder cancer patients were treated ...Objective: To investigate the significance of intrafascial neurovascular bundle spare technique in radical cystectomy. Methods: Between March 2010 and December 2011, a total of 26 bladder cancer patients were treated with radical cystectomy, and intrafascial neurovascular bundle spare technique was applied in all these patients. Mean age of 26 patients was 56.1 y (45 - 66). Among 26 patients, 21 cases were in stage T2, 5 cases were in stage T3. All patients choose Orthotopic neobladder as urinary diversion manner. We use intrafascial neurovascular bundle spare technique, dissect between prostatic fascial and prostatic capsule, spare neurovascular bundle. Operating time, blood loss, complications, continence and sexual function 3 months after surgery were recorded. Results: In all patients, mean operating time was 328 min, mean blood loss was 316 ml. Only 4 patients need transfusion during surgery. 1 case of urinary fistula was found after surgery, and spontaneously cured 10 days after surgery. 1 case of bowel obstruction was found, and was cured by conservative therapy. 4 cases of incontinence were found 3 months after surgery. 18 patients had a nomal erectile function 3 months after surgery. Conclusions: Intrafascial neurovascular bundle spare technique can safely and effectively reserve neurovascular bundle in radical cystectomy. Patients can reserve continence and erectile function by this technique.展开更多
Goal: The aim of this work is to study the relationship between the pneumatization of the adjacent structures of sphenoid sinuses and the protrusion of the neurovascular structures in the sinuses. Methods: A review of...Goal: The aim of this work is to study the relationship between the pneumatization of the adjacent structures of sphenoid sinuses and the protrusion of the neurovascular structures in the sinuses. Methods: A review of 225 CT scans skull was done for subjects aged at least 16 years old from November 1st to December 31st 2017. The pneumatization of adjacent structures of sphenoid sinuses and its relation with the protrusion of neurovascular structures surround the sinuses have been investigated. We used Fischer Exact test for comparison. The p value Results: Statistically significant associations were found between anterior clinoid process bilateral pneumatization and bilateral protrusion of carotid canal (p Conclusion: Compared to the literature, the prevalence of pneumatization of the adjacent structures of sphenoid sinuses was lower on Beninese than Caucasian and Asian. But there were the same correlations with the protrusion of neurovascular structures. In case of endonasal surgery of the sphenoid sinuses, surgeon should be aware of the high possibility the injury of optic nerves and internal carotid artery.展开更多
15 patients after the middle of 2018, during the initial onset of the epidemic of identified Nipah viral infection (fruits borne virus) in adjacent state, presented with fever, acute coma, delirium, movement disorders...15 patients after the middle of 2018, during the initial onset of the epidemic of identified Nipah viral infection (fruits borne virus) in adjacent state, presented with fever, acute coma, delirium, movement disorders, required referral to district headquarters hospital, for virology confirmation, and management. 135 mostly afebrile patients, who refused referral to government hospital, for virology confirmation, presented with symptoms of mainly subacute pan encephalitis, over the past 14 months;90% presented with conglomeration of vertigo, staring, personality changes, imbalance in gait, difficulty to walk, bilateral drooling of saliva, tremors, confusion, altered sensorium, nausea, vomiting;83% presented with dysarthria, 28% presented with symptoms of raised intracranial pressure-mimicking accelerated, malignant hypertensive emergencies, bradycardia, vomiting;decreased vision in 4.6%, myoclonic jerks in 58%, choreoathetosis in 8%. All of them could not afford INR 10000 for virology confirmation. Fruits borne viral subacute pan encephalitis, can present as subacute neurovascular syndrome, simulating ischemic stroke, mediated by Hapten triggered autoimmune angiopathy (blood borne) with resultant bilateral, asymmetrical multifocal, infarcts, cerebritis with consequent edema, requiring recognition, successful treatment with acyclovir, antiedema, antiepileptic measures and not antiplatelets, since the etiology is inflammatory and not degenerative. Promoting awareness to steam cook, pressure cook, cook with coconut oil (pie) fruits, steaming fresh fruit juices, before consumption will prevent incidence of fruits borne, tobacco leaves borne, and endemic viral infection. Economical screening card tests for Nipah fruits borne virus, will enable early detection, authenticate notification, early recognition treatment of subacute pan encephalitis presenting as neurovascular syndrome, mimicking ischemic stroke Global aborted blood pollution, contraceptive menstrual blood pollution, documented by rising environmental estrogen, beta human chorionic gonadotropins, alpha fetoprotein, favours emergence, virulence, drug resistance of microbes, including the recent fruits borne virus;global eradication of contraception, abortion (—non-evidence-based medical practice, without therapeutic indication, therapeutic protocols, therapeutic policies), to be replaced by global baby boom (promoting childbirth >10 - 20 children per family) will prevent further emergence, virulence of microbial infections, including Nipah, oncoming Ebola corona. Over the past 5 years, consumption of water living without scales, gills, fins,-toxin containing mammals, presented as cortical venous, sigmoid sinus thrombosis, in 3.5%, choreoathetosis in 12.5%, unresponsive but restless in 12.5%, quadriparesis, hemiparesis in 37.5% mimicking neurovascular syndrome, ischemic stroke;treatment with methylprednisolone, immunoglobulin reverted.展开更多
Background:The ex vivo model represented by mouse retinal explants in culture is a useful experimental model to investigate the molecular mechanism involved in neurovascular diseases such as diabetic retinopathy(DR).I...Background:The ex vivo model represented by mouse retinal explants in culture is a useful experimental model to investigate the molecular mechanism involved in neurovascular diseases such as diabetic retinopathy(DR).It ensures an experimental overview with more complete respect to isolate cells and reduce problems in terms of accessibility and management with respect to in vivo model.In particular,it allows the evaluation of the relationship between retinal cells in response to the typical stressors involved in DR pathogenesis.Methods:Ex vivo retinal fragments derived from 3-to 5-week-old C57BL/6J mice.In particular,after dissection,the retina is cut into 4 separate fragments and transferred onto inserts placed with ganglion cells up.Once in culture,the explants could be treated in stress conditions typical of DR.In particular,this study protocol describes the procedure for the preparation and the culture of retinal explants with specific metabolic stressors such as high glucose(HG),advanced glycation end product(AGE),and oxidative stress(OS).In the end,this paper provides the protocols to perform molecular analyses in order to evaluate the response of retinal explants to stress and/or neuroprotective treatments.Discussion:The cultured retinal explants represent an ex vivo experimental model to investigate the molecular mechanisms involved in neurovascular diseases such as DR.Moreover,they could be useful to test the effect of neuroprotective compounds in response to metabolic stressors in a fewer time respect to an in vivo model.In conclusion,retinal explants in culture represent a valuable experimental model to conduct further studies to better understand the pathophysiology of DR.展开更多
Purpose: Is to evaluate the accuracy of fused 3D time-of-flight (TOF) MR angiography and 3D Steady-State sequence (FIESTA) versus 3D contrast-enhanced T1 weighted images in evaluation of neurovascular compression via ...Purpose: Is to evaluate the accuracy of fused 3D time-of-flight (TOF) MR angiography and 3D Steady-State sequence (FIESTA) versus 3D contrast-enhanced T1 weighted images in evaluation of neurovascular compression via an inter-observer agreement protocol. Methods: Patients presented with trigeminal neuralgia, tinnitus, or facial hemispasm were examined using 3D-TOF-MRA, 3D-FIESTA, and 3D contrast-enhanced T1WI of the cerebellopontine angle to assess neurovascular compression. Two independent readers assessed the location, signal alteration, offending vascular structure, and grade of neurovascular compression using fused 3D-TOF-MRA and 3D-FIESTA versus contrast-enhanced T1 weighted images. The Kappa test for interobserver agreement was done. Results: The final study cohort consisted of 56 patients (42 females and 14 males) with a mean age of 38.25 ± 1.94. AICA was the offending vessel for 32 (57.1%) patients. The most common offending nerve was the trigeminal nerve in 26 patients, followed by facial/vestibulocochlear complex in 18 patients, and solely the 8th nerve in 12 patients. All three grades of compression were encountered in this study with percentages of 48.2% (27/56), 30.3% (17/56), and 21.4% (12/56) for grades I, II, III respectively. Fused TOF and steady-state images, and contrast-enhanced images showed perfect agreement for detection of the side of compression, the relation between nerve and vascular loop, offended neural segment, and offending vessel, while showing good agreement regarding the degree of compression. Conclusion: Fused TOF and steady-state images provide sufficient data to diagnose and grade microvascular compression syndromes comparable to contrast-enhanced images.展开更多
3D visualization was established for noninvasive evaluation of neurovascular compression syndromes. MR-CISS (constructive interference in the steady state) is the most potent image source to depict neurovascular detai...3D visualization was established for noninvasive evaluation of neurovascular compression syndromes. MR-CISS (constructive interference in the steady state) is the most potent image source to depict neurovascular details. The purpose of this article is the conceptual view over the established technique of 3D visualization in the topography of aneurysms in the posterior circulation in relation to surrounding cranial nerves and the brainstem.展开更多
Object:Parkinson disease(PD)is the second most common progressive neurodegenerative disorder.The available therapies for PD only treat the symptoms of the disease,without neuroprotective and disease-modifying effects....Object:Parkinson disease(PD)is the second most common progressive neurodegenerative disorder.The available therapies for PD only treat the symptoms of the disease,without neuroprotective and disease-modifying effects.Drugs that enhance intracerebral dopamine concentrations or stimulate dopamine receptors remain the mainstay of treatment for motor symptoms.Levodopa(L-DOPA)provides the greatest symptomatic benefit,but longterm using not only gradually loses its efficacy but also is associated with motor and non-motor complications,limiting function and reduce quality of life in PD patients,due to the disease progresses and medication.We previously showed that Rb fraction of ginsenosides blocks the PD progression and prevents the development and expression of L-DOPA-induced side effects.Given multiple cell types and impaired blood brain barrier(BBB)involve in the PD’S pathogenesis,this study further explores whether Rb alone or combined with L-DOPA could modify PD and protect neurovascular unit.Methods:Their anti-Parkinsonian activity was evaluated in rotenonelesioned rats.Rb and L-DOPA alone or both combination were given once a day 30 min before rotenone administration until occurrence of impaired motor function in controls,and motor deficits were surveyed at regular intervals.To determine potential persisted effect of treatments,at 3 days after stopping all the medications the last motor performances were tested and then brains were collected for assay of status of neurovascular unit and neuroinflammation.The protective effects of Rb,L-DOPA,and the combination were compared.Results:Rotenone-induced PD model rats displayed a series of motor behavior disorders,such as impaired forelimb grip,and lost balance,as well as reduced spontaneous activity and exploration behavior.Consistently,dopaminergic neuron terminals lost in dorsal-lateral striatum,while the cell bodies in the substantia nigra pars compacta largely spared,indicating dopamine nerve tip injury preceding cell body injury.This feature is highly consistent with clinical neuropathological changes in PD.Moreover,damaged astrocyte,activated microglia,and impaired BBB occurred in the striatum,with abundant infiltration of peripheral immune cells.Strikingly,Rb significantly prevented all those pathological behaviors,and morphological and cellular alterations,whereas L-DOPA only improved the motor performances of the PD rats and even exacerbated the BBB impairment.Interestingly,combination of Rb and L-DOPA showed the better protective effects than Rb alone,nearly completely blocking all the pathological manifestations.Conclusion:Rb,especially its combination with levodopa,can significantly prevent the development of PD.Direct protection of the components of neurovascular unit and consequently maintaining structural and neurochemical homeostasis may contribute to the disease-modifying effect of Rb.Our findings show a favorable application prospect of Rb,especially together with L-DOPA,in treating PD.展开更多
Activated protein C(APC), a natural anticoagulant, has been reported to exert direct vasculoprotective, neural protective, anti-inflammatory, and proneurogenic activities in the central nervous system. This study was ...Activated protein C(APC), a natural anticoagulant, has been reported to exert direct vasculoprotective, neural protective, anti-inflammatory, and proneurogenic activities in the central nervous system. This study was aimed to explore the neuroprotective effects and potential mechanisms of APC on the neurovascular unit of neonatal rats with intrauterine infection-induced white matter injury. Intraperitoneal injection of 300 μg/kg lipopolysaccharide(LPS) was administered consecutively to pregnant Sprague-Dawley rats at embryonic days 19 and 20 to establish the rat model of intrauterine infection-induced white matter injury. Control rats were injected with an equivalent amount of sterile saline on the same time. APC at the dosage of 0.2 mg/kg was intraperitoneally injected to neonatal rats immediately after birth. Brain tissues were collected at postnatal day 7 and stained with hematoxylin and eosin(H&E). Immunohistochemistry was used to evaluate myelin basic protein(MBP) expression in the periventricular white matter region. Blood-brain barrier(BBB) permeability and brain water content were measured using Evens Blue dye and wet/dry weight method. Double immunofluorescence staining and real-time quantitative PCR were performed to detect microglial activation and the expression of protease activated receptor 1(PAR1). Typical pathological changes of white matter injury were observed in rat brains exposed to LPS, and MBP expression in the periventricular region was significantly decreased. BBB was disrupted and the brain water content was increased. Microglia were largely activated and the m RNA and protein levels of PAR1 were elevated. APC administration ameliorated the pathological lesions of the white matter and increased MBP expression. BBB permeability and brain water content were reduced. Microglia activation was inhibited and the PAR1 m RNA and protein expression levels were both down-regulated. Our results suggested that APC exerted neuroprotective effects on multiple components of the neurovascular unit in neonatal rats with intrauterine infection-induced white matter injury, and the underlying mechanisms might involve decreased expression of PAR1.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81974207(to JH),82001383(to DW)the Special Clinical Research Project of Health Profession of Shanghai Municipal Health Commission,No.20204Y0076(to DW)。
文摘Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell proliferation and differentiation,thereby exerting neuroprotective effects.However,the beneficial effects of endogenous VEGFA/b FGF are limited as their expression is only transiently increased.In this study,we generated multilayered nanofiber membranes loaded with VEGFA/b FGF using layer-by-layer self-assembly and electrospinning techniques.We found that a membrane containing 10 layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1 month.This 10-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation,inhibited neuronal apoptosis,upregulated the expression of tight junction proteins,and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose deprivation.Furthermore,this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3(JAK2/STAT3),Bax/Bcl-2,and cleaved caspase-3.Therefore,this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.
基金supported by grants from the National Natural Science Foundation of China,No.81971231(to JL)Liaoning Revitalization Talents Program,No.XLYC1907178(to JL)。
文摘Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities,and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases.In the current research,the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model.Our results revealed that FTY-720 markedly decreased infarct volume,promoted neurological function recovery,and weakened the blood-brain barrier permeability of ischemic rats.The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels.These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.
基金supported by the Construction Project of Capacity Improvement Plan for Chongqing Municipal Health Commission affiliated unit [Grant No. (2019NLTS001) -ZS03174]the operating grant to Chongqing Key Laboratory of Neurodegenerative Diseases (Grant No.1000013)+1 种基金Chongqing Talent Project (Grant No.2000062),Overseas Students entrepreneurial fund (Grant No.2000079)Plan for High-level Talent Introduction (Grant No.2000055).
文摘An emerging concept termed the neurovascular unit(NVU)underlines neurovascular coupling.It has been reported that NVU impairment can result in neurodegenerative diseases,such as Alzheimer's disease and Parkinson's disease.Aging is a complex and irreversible process caused by programmed and damage-related factors.Loss of biological functions and increased susceptibility to additional neurodegenerative diseases are major characteristics of aging.In this review,we describe the basics of the NVU and discuss the effect of aging on NVU basics.Furthermore,we summarize the mechanisms that increase NVU susceptibility to neurodegenerative diseases,such as Alzheimer's disease and Parkinson's disease.Finally,we discuss new treatments for neurodegenerative diseases and methods of maintaining an intact NVU that may delay or diminish aging.
基金This work was supported by Project of Natural Science Foundation of Shandong province(No.ZR2020MH343).
文摘Background:Compatibility is a characteristic of the clinical application of traditional Chinese medicine,often leading to enhanced therapeutic effects.In the treatment of cerebral ischemia,blood-activating and open orifices herbs are frequently used individually;however,their combination is not commonly practiced.This study aims to investigate the impact of combining safflower and borneol as examples of open orifices herbs and blood-activating herbs on the neurovascular unit in rats with ischemic stroke.The objective is to determine whether this combination exhibits superior therapeutic efficacy compared to using borneol or safflower alone while exploring its underlying mechanism.These findings may provide novel insights for clinical treatments.Methods:SD male rats were randomly divided into 6 groups:sham operation group,model group,borneol group(0.1 g/kg),safflower group(5 g/kg),borneol combined with safflower group(0.1 g/kg+5 g/kg)and nimodipine group(0.01 g/kg).The middle cerebral artery cerebral ischemia(MCAO)model were prepared after continuous intragastric administration for 7 days in each group,the neurological function of each group were scored 24h after operation,and water content in brain tissue were measured by weighing method.The activity of superoxide dismutase(SOD)and the contents of nitric oxide(NO)and malondialdehyde(MDA)in brain tissue and serum were determined by spectrophotometry,and the mRNA expressions of matrix metalloproteinase 2(MMP-2),tight junction protein 1(ZO-1),vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF)were detected by Real time PCR.Result:Compared with the model group,the group treated with borneol combined with safflower exhibited a significant decrease in the neural function score of MCAO rats(P<0.01).Additionally,it led to a reduction in brain tissue water content(P<0.01),elevated SOD activity,and reduced levels of NO and MDA in both serum and brain tissue(P<0.01 or P<0.05).Moreover,this treatment resulted in a decrease in the mRNA expression of MMP-2 and an increase in ZO-1 in brain tissue,along with an increase in the mRNA expression of VEGF and BDNF(P<0.01).Conclusion:Borneol combined with safflower demonstrates a protective effect on the neurovascular unit in rats with ischemic stroke.This effect is likely associated with increased SOD activity,reduced MDA and NO content in both serum and brain tissue of MCAO rats,and a decrease in MMP-2 mRNA expression in brain tissue,coupled with an increase in ZO-1,VEGF,and BDNF mRNA expression.These effects were superior to those observed with borneol or safflower administered alone.
基金supported by the National Natural Science Foundation of China,No.81373578(to YHW),81573965(to YHW)the Natural Science Foundation of Hunan Province of China,No.2017JJ3241(to JL)the Education Department Scientific Research Foundation of Hunan Province of China,No.17C1229(to JL)
文摘Previous studies have shown that models of depression exhibit structural and functional changes to the neurovascular unit. Thus, we hypothesized that diabetes-related depression might be associated with damage to the hippocampal neurovascular unit. To test this hypothesis, neurons, astrocytes and endothelial cells were isolated from the brain tissues of rat embryos and newborn rats. Hippocampal neurovascular unit co-cultures were produced using the Transwell chamber co-culture system. A model of diabetes-related depression was generated by adding 150 mM glucose and 200 μM corticosterone to the culture system and compared with the neuron + astrocyte and astrocyte + endothelial cell co-culture systems. Western blot assay was used to measure levels of structural proteins in the hippocampal neurovascular unit co-culture system. Levels of basic fibroblast growth factor, angiogenic factor 1, glial cell line–derived neurotrophic factor, transforming growth factor β1, leukemia inhibitory factor and 5-hydroxytryptamine in the hippocampal neurovascular unit co-culture system were measured by enzyme-linked immunosorbent assay. Flow cytometry and terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick end labeling staining was used to assess neuronal apoptosis in the hippocampal neurovascular unit. The neurovascular unit triple cell co-culture system had better barrier function and higher levels of structural and secretory proteins than the double cell co-culture systems. In comparison, in the model of diabetes-related depression, the neurovascular unit was damaged with decreased barrier function, poor structural integrity and impaired secretory function. Moreover, neuronal apoptosis was markedly increased, and 5-hydroxytryptamine levels were reduced. These results suggest that diabetes-related depression is associated with structural and functional damage to the neurovascular unit. Our findings provide a foundation for further studies on the pathogenesis of diabetes-related depression.
基金supported by the National Natural Science Foundation of China,No.81430102(to QGW)
文摘Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression of neurotrophic factors. Therefore, HDCA may have therapeutic potential in the clinical management of ischemic stroke. This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine(approval No. BUCM-3-2016040201-2003) in April 2016.
基金Supported by the Science Foundation of Haikou Health Bureau (grant No.2010-SWY-13-058)Haikou Science Technology Information Bureau (grant No.2009-049-1)
文摘Objective:To describe the anatomical characteristics and patterns of neurovascular compression (NVC) in patients suffering trigeminal neuralgia(TN) by 3D high-resolution magnetic resonance imaging(MRI) method and image fusion technique.Methods:The anatomic structure of trigeminal nerve,brain stem and blood vessel was observed in 100 consecutive TN patients by 3D high resolution MRI(3D SPGR,contrast-enhanced T1 3D MP-RAGE and T2/T1 3D FIESTA). The 3D image sources were fused and visualized using 3D DOCTOR software.Results:One or several NVC sites,which usually appeared 0-9.8 mm away from brain stem,were found on the symptomatic side in 93%of the TN cases.Superior cerebellar artery was involved in 76%(71/93) of these cases.The other vessels including antero-inferior cerebellar artery,vertebral artery, basilar artery and veins also contributed to the occurrence of NVC.The NVC sites were found to be located in the proximal segment in 42%of these cases(39/93) and in the distal segment in 45% (42/93).Nerve dislocation or distortion was observed in 32%(30/93).Conclusions:Various 3D high resolution MRI methods combined with the image fusion technique could provide pathologic anatomic information for the diagnosis and treatment of TN.
基金This study was supported by the National Natural Science Foundation of China,Nos.81573965(to YHW),81874464(to YHW)the Natural Science Foundation of Hunan Province of China,No.2017JJ3241(to JL)the Education Department Scientific Research Foundation of Hunan Province of China,No.17C1229(to JL).
文摘Our previous studies have shown that glutamate and hippocampal neuron apoptosis are key signals and direct factors associated with diabetes-related depression,and structural and functional damage to the hippocampal neurovascular unit has been associated with diabetesrelated depression.However,the underlying mechanism remains unclear.We hypothesized that diabetes-related depression might be associated with the glutamate(Glu)/metabotropic glutamate receptor2/3(mGluR2/3)/phosphoinositide 3-kinase(PI3K)pathway,activated by glucocorticoid receptors in the hippocampal neurovascular unit.To test this hypothesis,rat hippocampal neurovascular unit models,containing hippocampal neurons,astrocytes,and brain microvascular endothelial cells,were treated with 150 mM glucose and 200μM corticosterone,to induce diabetes-related depression.Our results showed that under conditions of diabetes complicated by depression,hippocampal neurovascular units were damaged,leading to decreased barrier function;elevated Glu levels;upregulated glucocorticoid receptor,vesicular glutamate transporter 3(VGLUT-3),and metabotropic glutamate receptor 2/3(mGluR2/3)expression;downregulated excitatory amino acid transporter 1(EAAT-1)expression;and alteration of the balance of key proteins associated with the extracellular signal-regulated kinase(ERK)/glial cell-derived neurotrophic factor(GDNF)/PI3K signaling pathway.Moreover,the viability of neurons was dramatically reduced in the model of diabetes-related depression,and neuronal apoptosis,and caspase-3 and caspase-9 expression levels,were increased.Our results suggest that the Glu/mGluR2/3/PI3K pathway,induced by glucocorticoid receptor activation in the hippocampal neurovascular unit,may be associated with diabetes-related depression.This study was approved by the Laboratory Animal Ethics Committee of The First Hospital of Hunan University of Chinese Medicine,China(approval No.HN-ZYFY-2019-11-12)on November 12,2019.
基金supported by the Weston Brain Institute Rapid Response Grant,No.RR182093(to JR).
文摘The high metabolic demands of the brain require an efficient vascular system to be coupled with neural activity to supply adequate nutrients and oxygen.This supply is coordinated by the action of neurons,glial and vascular cells,known collectively as the neurovascular unit,which temporally and spatially regulate local cerebral blood flow through a process known as neurovascular coupling.In many neurodegenerative diseases,changes in functions of the neurovascular unit not only impair neurovascular coupling but also permeability of the blood-brain barrier,cerebral blood flow and clearance of waste from the brain.In order to study disease mechanisms,we need improved physiologicallyrelevant human models of the neurovascular unit.Advances towards modeling the cellular complexity of the neurovascular unit in vitro have been made using stem-cell derived organoids and more recently,vascularized organoids,enabling intricate studies of non-cell autonomous processes.Engineering and design innovations in microfluidic devices and tissue engineering are progressing our ability to interrogate the cerebrovasculature.These advanced models are being used to gain a better understanding of neurodegenerative disease processes and potential therapeutics.Continued innovation is required to build more physiologically-relevant models of the neurovascular unit encompassing both the cellular complexity and designed features to interrogate neurovascular unit functionality.
基金This study was partly supported by research grants from the National Natural Science Foundation of China,Nos.81802251(to KX),81772450(to HYZ)and 81801233(to YQW)the Natural Science Foundation of Zhejiang Province of China,Nos.LQ18H150003(to KX),LY19H150001(to DQC),LQ18H090011(to YQW)and LQ20C200015(to HJ)the Opening Project of Zhejiang Provincial Top Key Discipline of Pharmaceutical Sciences,No.YKFJ3-011(to KX).
文摘The blood-spinal cord barrier plays a vital role in recovery after spinal cord injury.The neurovascular unit concept emphasizes the relationship between nerves and vessels in the brain,while the effect of the blood-spinal cord barrier on the neurovascular unit is rarely reported in spinal cord injury studies.Mouse models of spinal cord injury were established by heavy object impact and then immediately injected with plateletderived growth factor(80μg/kg)at the injury site.Our results showed that after platelet-derived growth factor administration,spinal cord injury,neuronal apoptosis,and blood-spinal cord barrier permeability were reduced,excessive astrocyte proliferation and the autophagyrelated apoptosis signaling pathway were inhibited,collagen synthesis was increased,and mouse locomotor function was improved.In vitro,human umbilical vein endothelial cells were established by exposure to 200μM H2O2.At 2 hours prior to injury,in vitro cell models were treated with 5 ng/mL platelet-derived growth factor.Our results showed that expression of blood-spinal cord barrier-related proteins,including Occludin,Claudin 5,andβ-catenin,was significantly decreased and autophagy was significantly reduced.Additionally,the protective effects of platelet-derived growth factor could be reversed by intraperitoneal injection of 80 mg/kg chloroquine,an autophagy inhibitor,for 3 successive days prior to spinal cord injury.Our findings suggest that platelet-derived growth factor can promote endothelial cell repair by regulating autophagy,improve the function of the blood-spinal cord barrier,and promote the recovery of locomotor function post-spinal cord injury.Approval for animal experiments was obtained from the Animal Ethics Committee,Wenzhou Medical University,China(approval No.wydw2018-0043)in July 2018.
基金financially supported by the National Natural Science Foundation of China,Nos.82104412(to TD),81873023(to JW)Natural Science Basic Research Program of Shaanxi Province of China,No.2020JQ-865(to TD)+1 种基金Education Department of Shaanxi Province of China,No.20JK0597(to TD)the Subject Innovation Team of Shaanxi University of Chinese Medicine of China,No.2019-QN02(to PW).
文摘In 2001,the concept of the neurovascular unit was introduced at the Stroke Progress Review Group meeting.The neurovascular unit is an important element of the health and disease status of blood vessels and nerves in the central nervous system.Since then,the neurovascular unit has attracted increasing interest from research teams,who have contributed greatly to the prevention,treatment,and prognosis of stroke and neurodegenerative diseases.However,additional research is needed to establish an efficient,low-cost,and low-energy in vitro model of the neurovascular unit,as well as enable noninvasive observation of neurovascular units in vivo and in vitro.In this review,we first summarize the composition of neurovascular units,then investigate the efficacy of different types of stem cells and cell culture methods in the construction of neurovascular unit models,and finally assess the progress of imaging methods used to observe neurovascular units in recent years and their positive role in the monitoring and investigation of the mechanisms of a variety of central nervous system diseases.
基金supported by the Stem Cell Clinical Research Project of China,No.CMR-20161129-1003Liaoning Province Excellent Talent Program Project of China,No.XLYC1902031the Dalian Innovation Technology Foundation of China,No.2018J11CY025(all to JL).
文摘Biological studies typically rely on a simple monolayer cell culture,which does not reflect the complex functional characteristics of human tissues and organs,or their real response to external stimuli.Microfluidic technology has advantages of high-throughput screening,accurate control of the fluid velocity,low cell consumption,long-term culture,and high integration.By combining the multipotential differentiation of neural stem cells with high throughput and the integrated characteristics of microfluidic technology,an in vitro model of a functionalized neurovascular unit was established using human neural stem cell-derived neurons,astrocytes,oligodendrocytes,and a functional microvascular barrier.The model comprises a multi-layer vertical neural module and vascular module,both of which were connected with a syringe pump.This provides controllable conditions for cell inoculation and nutrient supply,and simultaneously simulates the process of ischemic/hypoxic injury and the process of inflammatory factors in the circulatory system passing through the blood-brain barrier and then acting on the nerve tissue in the brain.The in vitro functionalized neurovascular unit model will be conducive to central nervous system disease research,drug screening,and new drug development.
文摘Objective: To investigate the significance of intrafascial neurovascular bundle spare technique in radical cystectomy. Methods: Between March 2010 and December 2011, a total of 26 bladder cancer patients were treated with radical cystectomy, and intrafascial neurovascular bundle spare technique was applied in all these patients. Mean age of 26 patients was 56.1 y (45 - 66). Among 26 patients, 21 cases were in stage T2, 5 cases were in stage T3. All patients choose Orthotopic neobladder as urinary diversion manner. We use intrafascial neurovascular bundle spare technique, dissect between prostatic fascial and prostatic capsule, spare neurovascular bundle. Operating time, blood loss, complications, continence and sexual function 3 months after surgery were recorded. Results: In all patients, mean operating time was 328 min, mean blood loss was 316 ml. Only 4 patients need transfusion during surgery. 1 case of urinary fistula was found after surgery, and spontaneously cured 10 days after surgery. 1 case of bowel obstruction was found, and was cured by conservative therapy. 4 cases of incontinence were found 3 months after surgery. 18 patients had a nomal erectile function 3 months after surgery. Conclusions: Intrafascial neurovascular bundle spare technique can safely and effectively reserve neurovascular bundle in radical cystectomy. Patients can reserve continence and erectile function by this technique.
文摘Goal: The aim of this work is to study the relationship between the pneumatization of the adjacent structures of sphenoid sinuses and the protrusion of the neurovascular structures in the sinuses. Methods: A review of 225 CT scans skull was done for subjects aged at least 16 years old from November 1st to December 31st 2017. The pneumatization of adjacent structures of sphenoid sinuses and its relation with the protrusion of neurovascular structures surround the sinuses have been investigated. We used Fischer Exact test for comparison. The p value Results: Statistically significant associations were found between anterior clinoid process bilateral pneumatization and bilateral protrusion of carotid canal (p Conclusion: Compared to the literature, the prevalence of pneumatization of the adjacent structures of sphenoid sinuses was lower on Beninese than Caucasian and Asian. But there were the same correlations with the protrusion of neurovascular structures. In case of endonasal surgery of the sphenoid sinuses, surgeon should be aware of the high possibility the injury of optic nerves and internal carotid artery.
文摘15 patients after the middle of 2018, during the initial onset of the epidemic of identified Nipah viral infection (fruits borne virus) in adjacent state, presented with fever, acute coma, delirium, movement disorders, required referral to district headquarters hospital, for virology confirmation, and management. 135 mostly afebrile patients, who refused referral to government hospital, for virology confirmation, presented with symptoms of mainly subacute pan encephalitis, over the past 14 months;90% presented with conglomeration of vertigo, staring, personality changes, imbalance in gait, difficulty to walk, bilateral drooling of saliva, tremors, confusion, altered sensorium, nausea, vomiting;83% presented with dysarthria, 28% presented with symptoms of raised intracranial pressure-mimicking accelerated, malignant hypertensive emergencies, bradycardia, vomiting;decreased vision in 4.6%, myoclonic jerks in 58%, choreoathetosis in 8%. All of them could not afford INR 10000 for virology confirmation. Fruits borne viral subacute pan encephalitis, can present as subacute neurovascular syndrome, simulating ischemic stroke, mediated by Hapten triggered autoimmune angiopathy (blood borne) with resultant bilateral, asymmetrical multifocal, infarcts, cerebritis with consequent edema, requiring recognition, successful treatment with acyclovir, antiedema, antiepileptic measures and not antiplatelets, since the etiology is inflammatory and not degenerative. Promoting awareness to steam cook, pressure cook, cook with coconut oil (pie) fruits, steaming fresh fruit juices, before consumption will prevent incidence of fruits borne, tobacco leaves borne, and endemic viral infection. Economical screening card tests for Nipah fruits borne virus, will enable early detection, authenticate notification, early recognition treatment of subacute pan encephalitis presenting as neurovascular syndrome, mimicking ischemic stroke Global aborted blood pollution, contraceptive menstrual blood pollution, documented by rising environmental estrogen, beta human chorionic gonadotropins, alpha fetoprotein, favours emergence, virulence, drug resistance of microbes, including the recent fruits borne virus;global eradication of contraception, abortion (—non-evidence-based medical practice, without therapeutic indication, therapeutic protocols, therapeutic policies), to be replaced by global baby boom (promoting childbirth >10 - 20 children per family) will prevent further emergence, virulence of microbial infections, including Nipah, oncoming Ebola corona. Over the past 5 years, consumption of water living without scales, gills, fins,-toxin containing mammals, presented as cortical venous, sigmoid sinus thrombosis, in 3.5%, choreoathetosis in 12.5%, unresponsive but restless in 12.5%, quadriparesis, hemiparesis in 37.5% mimicking neurovascular syndrome, ischemic stroke;treatment with methylprednisolone, immunoglobulin reverted.
文摘Background:The ex vivo model represented by mouse retinal explants in culture is a useful experimental model to investigate the molecular mechanism involved in neurovascular diseases such as diabetic retinopathy(DR).It ensures an experimental overview with more complete respect to isolate cells and reduce problems in terms of accessibility and management with respect to in vivo model.In particular,it allows the evaluation of the relationship between retinal cells in response to the typical stressors involved in DR pathogenesis.Methods:Ex vivo retinal fragments derived from 3-to 5-week-old C57BL/6J mice.In particular,after dissection,the retina is cut into 4 separate fragments and transferred onto inserts placed with ganglion cells up.Once in culture,the explants could be treated in stress conditions typical of DR.In particular,this study protocol describes the procedure for the preparation and the culture of retinal explants with specific metabolic stressors such as high glucose(HG),advanced glycation end product(AGE),and oxidative stress(OS).In the end,this paper provides the protocols to perform molecular analyses in order to evaluate the response of retinal explants to stress and/or neuroprotective treatments.Discussion:The cultured retinal explants represent an ex vivo experimental model to investigate the molecular mechanisms involved in neurovascular diseases such as DR.Moreover,they could be useful to test the effect of neuroprotective compounds in response to metabolic stressors in a fewer time respect to an in vivo model.In conclusion,retinal explants in culture represent a valuable experimental model to conduct further studies to better understand the pathophysiology of DR.
文摘Purpose: Is to evaluate the accuracy of fused 3D time-of-flight (TOF) MR angiography and 3D Steady-State sequence (FIESTA) versus 3D contrast-enhanced T1 weighted images in evaluation of neurovascular compression via an inter-observer agreement protocol. Methods: Patients presented with trigeminal neuralgia, tinnitus, or facial hemispasm were examined using 3D-TOF-MRA, 3D-FIESTA, and 3D contrast-enhanced T1WI of the cerebellopontine angle to assess neurovascular compression. Two independent readers assessed the location, signal alteration, offending vascular structure, and grade of neurovascular compression using fused 3D-TOF-MRA and 3D-FIESTA versus contrast-enhanced T1 weighted images. The Kappa test for interobserver agreement was done. Results: The final study cohort consisted of 56 patients (42 females and 14 males) with a mean age of 38.25 ± 1.94. AICA was the offending vessel for 32 (57.1%) patients. The most common offending nerve was the trigeminal nerve in 26 patients, followed by facial/vestibulocochlear complex in 18 patients, and solely the 8th nerve in 12 patients. All three grades of compression were encountered in this study with percentages of 48.2% (27/56), 30.3% (17/56), and 21.4% (12/56) for grades I, II, III respectively. Fused TOF and steady-state images, and contrast-enhanced images showed perfect agreement for detection of the side of compression, the relation between nerve and vascular loop, offended neural segment, and offending vessel, while showing good agreement regarding the degree of compression. Conclusion: Fused TOF and steady-state images provide sufficient data to diagnose and grade microvascular compression syndromes comparable to contrast-enhanced images.
文摘3D visualization was established for noninvasive evaluation of neurovascular compression syndromes. MR-CISS (constructive interference in the steady state) is the most potent image source to depict neurovascular details. The purpose of this article is the conceptual view over the established technique of 3D visualization in the topography of aneurysms in the posterior circulation in relation to surrounding cranial nerves and the brainstem.
文摘Object:Parkinson disease(PD)is the second most common progressive neurodegenerative disorder.The available therapies for PD only treat the symptoms of the disease,without neuroprotective and disease-modifying effects.Drugs that enhance intracerebral dopamine concentrations or stimulate dopamine receptors remain the mainstay of treatment for motor symptoms.Levodopa(L-DOPA)provides the greatest symptomatic benefit,but longterm using not only gradually loses its efficacy but also is associated with motor and non-motor complications,limiting function and reduce quality of life in PD patients,due to the disease progresses and medication.We previously showed that Rb fraction of ginsenosides blocks the PD progression and prevents the development and expression of L-DOPA-induced side effects.Given multiple cell types and impaired blood brain barrier(BBB)involve in the PD’S pathogenesis,this study further explores whether Rb alone or combined with L-DOPA could modify PD and protect neurovascular unit.Methods:Their anti-Parkinsonian activity was evaluated in rotenonelesioned rats.Rb and L-DOPA alone or both combination were given once a day 30 min before rotenone administration until occurrence of impaired motor function in controls,and motor deficits were surveyed at regular intervals.To determine potential persisted effect of treatments,at 3 days after stopping all the medications the last motor performances were tested and then brains were collected for assay of status of neurovascular unit and neuroinflammation.The protective effects of Rb,L-DOPA,and the combination were compared.Results:Rotenone-induced PD model rats displayed a series of motor behavior disorders,such as impaired forelimb grip,and lost balance,as well as reduced spontaneous activity and exploration behavior.Consistently,dopaminergic neuron terminals lost in dorsal-lateral striatum,while the cell bodies in the substantia nigra pars compacta largely spared,indicating dopamine nerve tip injury preceding cell body injury.This feature is highly consistent with clinical neuropathological changes in PD.Moreover,damaged astrocyte,activated microglia,and impaired BBB occurred in the striatum,with abundant infiltration of peripheral immune cells.Strikingly,Rb significantly prevented all those pathological behaviors,and morphological and cellular alterations,whereas L-DOPA only improved the motor performances of the PD rats and even exacerbated the BBB impairment.Interestingly,combination of Rb and L-DOPA showed the better protective effects than Rb alone,nearly completely blocking all the pathological manifestations.Conclusion:Rb,especially its combination with levodopa,can significantly prevent the development of PD.Direct protection of the components of neurovascular unit and consequently maintaining structural and neurochemical homeostasis may contribute to the disease-modifying effect of Rb.Our findings show a favorable application prospect of Rb,especially together with L-DOPA,in treating PD.
基金supported by grants from National Natural Science Foundation of China(No.81471519 and No.81401277)the Program for Changjiang Scholars and Innovative Research Team in University of China(No.IRT_14R20)
文摘Activated protein C(APC), a natural anticoagulant, has been reported to exert direct vasculoprotective, neural protective, anti-inflammatory, and proneurogenic activities in the central nervous system. This study was aimed to explore the neuroprotective effects and potential mechanisms of APC on the neurovascular unit of neonatal rats with intrauterine infection-induced white matter injury. Intraperitoneal injection of 300 μg/kg lipopolysaccharide(LPS) was administered consecutively to pregnant Sprague-Dawley rats at embryonic days 19 and 20 to establish the rat model of intrauterine infection-induced white matter injury. Control rats were injected with an equivalent amount of sterile saline on the same time. APC at the dosage of 0.2 mg/kg was intraperitoneally injected to neonatal rats immediately after birth. Brain tissues were collected at postnatal day 7 and stained with hematoxylin and eosin(H&E). Immunohistochemistry was used to evaluate myelin basic protein(MBP) expression in the periventricular white matter region. Blood-brain barrier(BBB) permeability and brain water content were measured using Evens Blue dye and wet/dry weight method. Double immunofluorescence staining and real-time quantitative PCR were performed to detect microglial activation and the expression of protease activated receptor 1(PAR1). Typical pathological changes of white matter injury were observed in rat brains exposed to LPS, and MBP expression in the periventricular region was significantly decreased. BBB was disrupted and the brain water content was increased. Microglia were largely activated and the m RNA and protein levels of PAR1 were elevated. APC administration ameliorated the pathological lesions of the white matter and increased MBP expression. BBB permeability and brain water content were reduced. Microglia activation was inhibited and the PAR1 m RNA and protein expression levels were both down-regulated. Our results suggested that APC exerted neuroprotective effects on multiple components of the neurovascular unit in neonatal rats with intrauterine infection-induced white matter injury, and the underlying mechanisms might involve decreased expression of PAR1.
