Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process...Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.展开更多
Bone tissue relies on the intricate interplay between blood vessels and nerve fibers,both are essential for many physiological and pathological processes of the skeletal system.Blood vessels provide the necessary oxyg...Bone tissue relies on the intricate interplay between blood vessels and nerve fibers,both are essential for many physiological and pathological processes of the skeletal system.Blood vessels provide the necessary oxygen and nutrients to nerve and bone tissues,and remove metabolic waste.Concomitantly,nerve fibers precede blood vessels during growth,promote vascularization,and influence bone cells by secreting neurotransmitters to stimulate osteogenesis.Despite the critical roles of both components,current biomaterials generally focus on enhancing intraosseous blood vessel repair,while often neglecting the contribution of nerves.Understanding the distribution and main functions of blood vessels and nerve fibers in bone is crucial for developing effective biomaterials for bone tissue engineering.This review first explores the anatomy of intraosseous blood vessels and nerve fibers,highlighting their vital roles in bone embryonic development,metabolism,and repair.It covers innovative bone regeneration strategies directed at accelerating the intrabony neurovascular system over the past 10 years.The issues covered included material properties(stiffness,surface topography,pore structures,conductivity,and piezoelectricity)and acellular biological factors[neurotrophins,peptides,ribonucleic acids(RNAs),inorganic ions,and exosomes].Major challenges encountered by neurovascularized materials during their clinical translation have also been highlighted.Furthermore,the review discusses future research directions and potential developments aimed at producing bone repair materials that more accurately mimic the natural healing processes of bone tissue.This review will serve as a valuable reference for researchers and clinicians in developing novel neurovascularized biomaterials and accelerating their translation into clinical practice.By bridging the gap between experimental research and practical application,these advancements have the potential to transform the treatment of bone defects and significantly improve the quality of life for patients with bone-related conditions.展开更多
Calvarial nerves,along with vasculature,influence skull formation during development and following injury,but it remains unclear how calvarial nerves are spatially distributed during postnatal growth and aging.Studyin...Calvarial nerves,along with vasculature,influence skull formation during development and following injury,but it remains unclear how calvarial nerves are spatially distributed during postnatal growth and aging.Studying the spatial distribution of nerves in the skull remains a challenge due to a lack of methods to quantify 3D structures in intact bone.To visualize calvarial 3D neurovascular architecture,we imaged nerves and endothelial cells with lightsheet microscopy.展开更多
Neurovascularization serves as the prerequisite and assurance for fostering neurogenesis after peripheral nerve injury(PNI),not only contributing to the reconstruction of the regenerative neurovascular niche but also ...Neurovascularization serves as the prerequisite and assurance for fostering neurogenesis after peripheral nerve injury(PNI),not only contributing to the reconstruction of the regenerative neurovascular niche but also providing a surface and directionality for Schwann cell(SC)cords migration and axons elongation.Despite the development of nerve tissue engineering techniques has drawn increasing attention to the intervention approach for repairing nerve defects,systematic generalization summary of the efficient intervention to expedite nerve angiogenesis is still scarce.This review delves into the mechanisms by which macrophages within the nerve defect trigger angiogenesis after PNI and elucidates how the newborn vessels support nerve regeneration,and then extracts three major categories of strategies for producing vascularized nerves in vitro and in vivo from them,encompassing(1)in vitro prevascularization,(2)in vivo prevascularization,and(3)stimulation of neurovascularization in situ.Furthermore,we emphasize that the lack of accuracy for structure and spatiotemporal regulation,as well as the operational inconvenience and delayed connection to the host's nerve stumps,have stuck the existing neurovascularization technology in the preclinical stage.The successful design of a future prospective clinical vascularized nerve scaffold should be guided by a comprehensive consideration of these aspects.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
Houshiheisan is composed of wind-dispelling （chrysanthemun fower, divaricate saposhnikovia root, Manchurian wild ginger, cassia twig, Szechwan lovage rhizome, and platycodon root） and deficiency-nourishing （ginseng...Houshiheisan is composed of wind-dispelling （chrysanthemun fower, divaricate saposhnikovia root, Manchurian wild ginger, cassia twig, Szechwan lovage rhizome, and platycodon root） and deficiency-nourishing （ginseng, Chinese angelica, large-head atractylodes rhizome, Indian bread, and zingiber） drugs. In this study, we assumed these drugs have protective effects against cerebral ischemia, on neurovascular units. Houshiheisan was intragastrically administered in a rat model of focal cerebral ischemia. Hematoxylin-eosin staining, transmission electron microscopy, immu- nofluorescence staining, and western blot assays showed that Houshiheisan reduced pathological injury to the ischemic penumbra, protected neurovascular units, visibly up-regtflated neuronal nuclear antigen expression, and down-regulated amyloid precursor protein and amyloid-[3 42 expression. Wind-dispelling and deficiency-nourishing drugs maintained NeuN expression to varying degrees, but did not affect amyloid precursor protein or amyloid-~ 42 expression in the ischemic penumbra. Our results suggest that the compound prescription Houshiheisan effectively suppresses abnormal amyloid precursor protein accumulation, reduces amyloid substance depo- sition, maintains stabilization of the internal environment of neurovascular units, and minimizes injury to neurovascular units in the ischemic penumbra.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
Objective:To investigate the role of iptakalim,an ATP-sensitive potassium channel opener,in transient cerebral ischemia/reperfusion (I/R) injury and its involved mechanisms.Methods:Intraluminal occlusion of middle cer...Objective:To investigate the role of iptakalim,an ATP-sensitive potassium channel opener,in transient cerebral ischemia/reperfusion (I/R) injury and its involved mechanisms.Methods:Intraluminal occlusion of middle cerebral artery (MCAO) in a rat model was used to investigate the effect of iptakalim at different time points.Infarct volume was measured by staining with 2,3,5-triphenyltetrazolium chloride,and immunohistochemistry was used to evaluate the expressions of Bcl-2 and Bax.In vitro,neurovascular unit (NVU) cells,including rat primary cortical neurons,astrocytes,and cerebral microvascular endothelial cells,were cultured and underwent oxygen-glucose deprivation (OGD).The protective effect of iptakalim on NVU cells was investigated by cell viability and injury assessments,which were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and release of lactate dehydrogenase.Caspase-3,Bcl-2 and Bax mRNA expressions were evaluated by real-time polymerase chain reaction (PCR).Results:Administration of iptakalim 0 or 1 h after reperfusion significantly reduced infarct volumes,improved neurological scores,and attenuated brain edema after cerebral I/R injury.Iptakalim treatment (0 h after reperfusion) also reduced caspase-3 expression and increased the ratio of Bcl-2 to Bax by immunohistochemistry.Iptakalim inhibited OGD-induced cell death in cultured neurons and astrocytes,and lactate dehydrogenase release from cerebral microvascular endothelial cells.Iptakalim reduced mRNA expression of caspase-3 and increased the ratio of Bcl-2 to Bax in NVU cells.Conclusions:Iptakalim confers neuroprotection against cerebral I/R injury by protecting NVU cells via inhibiting of apoptosis.展开更多
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
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 neurovascular bundle of the prostate and cavernosal nerves have been used to describe the same structure ever since the publication of the first studies on the neuroanatomy of the lower urogenital tract of men, st...The neurovascular bundle of the prostate and cavernosal nerves have been used to describe the same structure ever since the publication of the first studies on the neuroanatomy of the lower urogenital tract of men, studies that were prompted by postoperative complications arising from radical prostatectomy. In urological surgery every effort is made to preserve or restore the neurovascular bundle of the prostate to avoid erectile dysfunction （ED）. However, the postoperative potency rates are yet to be satisfactory despite all advancements in radical prostatectomy technique. As the technology associated with urological surgery develops and topographical studies on neuroanatomy are cultivated, new observations seriously challenge the classical teachings on the topography of the neurovascular bundle of the prostate and the cavernosal nerves. The present review revisits the classical and most recent data on the topographical anatomy of the neurovascular bundle of the prostate prostatectomy techniques.展开更多
Summary： Activated protein C （APC）, a natural anticoagulant, has been reported to exert direct vascu- loprotective, neural protective, anti-inflammatory, and proneurogenic activities in the central nervous system. ...Summary： Activated protein C （APC）, a natural anticoagulant, has been reported to exert direct vascu- loprotective, 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. In- traperitoneal injection of 300 ~tg/kg lipopolysaccharide （LPS） was administered consecutively to preg- nant Sprague-Dawley rats at embryonic days 19 and 20 to establish the rat model of intrauterine infec- tion-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 imme- diately after birth. Brain tissues were collected at postnatal day 7 and stained with hematoxylin and eo- sin （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 ob- served 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 acti- vated and the mRNA 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 mRNA and protein ex- pression levels were both down-regulated. Our results suggested that APC exerted neuroprotective ef- fects on multiple components of the neurovascular unit in neonatal rats with intrauterine infec- tion-induced white matter injury, and the underlying mechanisms might involve decreased expression of PAR1.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
Epilepsy is a multifaceted neurological syndrome characterized by recurrent,spontaneous,and synchronous seizures.The pathogenesis of epilepsy,known as epileptogenesis,involves intricate changes in neurons,neuroglia,an...Epilepsy is a multifaceted neurological syndrome characterized by recurrent,spontaneous,and synchronous seizures.The pathogenesis of epilepsy,known as epileptogenesis,involves intricate changes in neurons,neuroglia,and endothelium,leading to structural and functional disorders within neurovascular units and culminating in the development of spontaneous epilepsy.Although current research on epilepsy treatments primarily centers around anti-seizure drugs,it is imperative to seek effective interventions capable of disrupting epileptogenesis.To this end,a comprehensive exploration of the changes and the molecular mechanisms underlying epileptogenesis holds the promise of identifying vital biomarkers for accurate diagnosis and potential therapeutic targets.Emphasizing early diagnosis and timely intervention is paramount,as it stands to significantly improve patient prognosis and alleviate the socioeconomic burden.In this review,we highlight the changes and molecular mechanisms of the neurovascular unit in epileptogenesis and provide a theoretical basis for identifying biomarkers and drug targets.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
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
The objective of this study was to compare the outcomes of the modified Nesbit procedure using different techniques for dissecting the neurovascular bundle （NVB） to correct ventral congenital penile curvatures （CPC...The objective of this study was to compare the outcomes of the modified Nesbit procedure using different techniques for dissecting the neurovascular bundle （NVB） to correct ventral congenital penile curvatures （CPCs）. The bundle was mobilized using the medial and lateral dissection technique in 21 （Group 1） and 13 （Group 2） patients, respectively. In the medial technique, Buck＇s fascia is opened at the dorsal side of the penis, the deep dorsal vein is removed at the most prominent site of the curvature and a diamond-shaped tunica albuginea （TA） is excised from the midline of the penis. In the lateral technique, the bundle is mobilized using a longitudinal lateral incision of the Buck＇s fascia above the urethra at the 5 and 7 o＇clock positions via a bilateral approach. The localization and degree of curvature was evaluated using the combined intracavernous injection stimulation test or from the patients＇ photographs. The mean patient age and degree of curvature were similar between groups. The mean operation time was longer for Group 2 （P= 0.01）. In Group 1, nine patients （42.8%） required one diamond excision, 10 （47.6%） required two diamond excisions and two （9.5%） required more than two excisions; in Group 2, six patients （46.2%） required two diamond excisions and seven patients （53.8%） required more than two diamond excisions （P = 0.019）. The differences in penile shortening, penile straightening and numbness of the glans penis were not statistically significant. Medial dissection of the bundle for the modified Nesbit procedure reduces the number of diamond-shaped removals of TA and thus shortens operation time in comparison with its lateral counterpart.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82171344(to ZY),82471313(to CKT)the Guangdong Basic and Applied Basic Research Foundation,China,Nos.2023B1515120035,2024A1515012035(to CKT)The Science and Technology Projects in Guangzhou Nos.2025A03J4169(to ZY)。
文摘Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.
基金supported by the Foundation of National Clinical Research Center for Oral Diseases(LCA202204)the Key Research and Development Program of Shaanxi(2024GH-YBXM-19)+7 种基金the Clinical New Technology Program of Air Force Medical University(LX2023-306)the China Postdoctoral Science Foundation(2019M653969)the Thousand Talents Plan of Shaanxi Province(to Jing Wang)the National Natural Science Foundation of China(82101069,22205257)the Logistics Independent Research Project of PLA(to Yang Jiao)the Beijing Natural Science Foundation(7242279),the Beijing Nova Program(20230484283)the Beijing Municipal Science&Technology Commission(Z221100007422130)the Open Project of State Key Laboratory of Trauma and Chemical poisoning(SKLO202401).
文摘Bone tissue relies on the intricate interplay between blood vessels and nerve fibers,both are essential for many physiological and pathological processes of the skeletal system.Blood vessels provide the necessary oxygen and nutrients to nerve and bone tissues,and remove metabolic waste.Concomitantly,nerve fibers precede blood vessels during growth,promote vascularization,and influence bone cells by secreting neurotransmitters to stimulate osteogenesis.Despite the critical roles of both components,current biomaterials generally focus on enhancing intraosseous blood vessel repair,while often neglecting the contribution of nerves.Understanding the distribution and main functions of blood vessels and nerve fibers in bone is crucial for developing effective biomaterials for bone tissue engineering.This review first explores the anatomy of intraosseous blood vessels and nerve fibers,highlighting their vital roles in bone embryonic development,metabolism,and repair.It covers innovative bone regeneration strategies directed at accelerating the intrabony neurovascular system over the past 10 years.The issues covered included material properties(stiffness,surface topography,pore structures,conductivity,and piezoelectricity)and acellular biological factors[neurotrophins,peptides,ribonucleic acids(RNAs),inorganic ions,and exosomes].Major challenges encountered by neurovascularized materials during their clinical translation have also been highlighted.Furthermore,the review discusses future research directions and potential developments aimed at producing bone repair materials that more accurately mimic the natural healing processes of bone tissue.This review will serve as a valuable reference for researchers and clinicians in developing novel neurovascularized biomaterials and accelerating their translation into clinical practice.By bridging the gap between experimental research and practical application,these advancements have the potential to transform the treatment of bone defects and significantly improve the quality of life for patients with bone-related conditions.
基金supported by funding from NIDCR(1R01DE027957)Maryland Stem Cell Research Fund(2022-MSCRFV-5782)the NSF GRFP and NCI(5R01CA237597-05,2R01CA196701-06A1).
文摘Calvarial nerves,along with vasculature,influence skull formation during development and following injury,but it remains unclear how calvarial nerves are spatially distributed during postnatal growth and aging.Studying the spatial distribution of nerves in the skull remains a challenge due to a lack of methods to quantify 3D structures in intact bone.To visualize calvarial 3D neurovascular architecture,we imaged nerves and endothelial cells with lightsheet microscopy.
基金financially supported by the following programs:National Key Research and Development Program of China(No.2023YFB3813003)National Natural Science Foundation of China(Nos.82430031,82122014,82071085)+1 种基金Zhejiang Provincial Natural Science Foundation of China(No.LR21H140001)the Central Universities(No.2022FZZX01-33)。
文摘Neurovascularization serves as the prerequisite and assurance for fostering neurogenesis after peripheral nerve injury(PNI),not only contributing to the reconstruction of the regenerative neurovascular niche but also providing a surface and directionality for Schwann cell(SC)cords migration and axons elongation.Despite the development of nerve tissue engineering techniques has drawn increasing attention to the intervention approach for repairing nerve defects,systematic generalization summary of the efficient intervention to expedite nerve angiogenesis is still scarce.This review delves into the mechanisms by which macrophages within the nerve defect trigger angiogenesis after PNI and elucidates how the newborn vessels support nerve regeneration,and then extracts three major categories of strategies for producing vascularized nerves in vitro and in vivo from them,encompassing(1)in vitro prevascularization,(2)in vivo prevascularization,and(3)stimulation of neurovascularization in situ.Furthermore,we emphasize that the lack of accuracy for structure and spatiotemporal regulation,as well as the operational inconvenience and delayed connection to the host's nerve stumps,have stuck the existing neurovascularization technology in the preclinical stage.The successful design of a future prospective clinical vascularized nerve scaffold should be guided by a comprehensive consideration of these aspects.
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supported by the National Natural Science Foundation of China,No.30973782,81373526the Natural Science Foundation of Beijing,No.7102014,7122018the Beijing Municipal Higher Learning Institution Talent Teaching Plan"Young and Middle-aged Talented People Training"Project,No.PXM2011014226
文摘Houshiheisan is composed of wind-dispelling （chrysanthemun fower, divaricate saposhnikovia root, Manchurian wild ginger, cassia twig, Szechwan lovage rhizome, and platycodon root） and deficiency-nourishing （ginseng, Chinese angelica, large-head atractylodes rhizome, Indian bread, and zingiber） drugs. In this study, we assumed these drugs have protective effects against cerebral ischemia, on neurovascular units. Houshiheisan was intragastrically administered in a rat model of focal cerebral ischemia. Hematoxylin-eosin staining, transmission electron microscopy, immu- nofluorescence staining, and western blot assays showed that Houshiheisan reduced pathological injury to the ischemic penumbra, protected neurovascular units, visibly up-regtflated neuronal nuclear antigen expression, and down-regulated amyloid precursor protein and amyloid-[3 42 expression. Wind-dispelling and deficiency-nourishing drugs maintained NeuN expression to varying degrees, but did not affect amyloid precursor protein or amyloid-~ 42 expression in the ischemic penumbra. Our results suggest that the compound prescription Houshiheisan effectively suppresses abnormal amyloid precursor protein accumulation, reduces amyloid substance depo- sition, maintains stabilization of the internal environment of neurovascular units, and minimizes injury to neurovascular units in the ischemic penumbra.
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.
文摘Objective:To investigate the role of iptakalim,an ATP-sensitive potassium channel opener,in transient cerebral ischemia/reperfusion (I/R) injury and its involved mechanisms.Methods:Intraluminal occlusion of middle cerebral artery (MCAO) in a rat model was used to investigate the effect of iptakalim at different time points.Infarct volume was measured by staining with 2,3,5-triphenyltetrazolium chloride,and immunohistochemistry was used to evaluate the expressions of Bcl-2 and Bax.In vitro,neurovascular unit (NVU) cells,including rat primary cortical neurons,astrocytes,and cerebral microvascular endothelial cells,were cultured and underwent oxygen-glucose deprivation (OGD).The protective effect of iptakalim on NVU cells was investigated by cell viability and injury assessments,which were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and release of lactate dehydrogenase.Caspase-3,Bcl-2 and Bax mRNA expressions were evaluated by real-time polymerase chain reaction (PCR).Results:Administration of iptakalim 0 or 1 h after reperfusion significantly reduced infarct volumes,improved neurological scores,and attenuated brain edema after cerebral I/R injury.Iptakalim treatment (0 h after reperfusion) also reduced caspase-3 expression and increased the ratio of Bcl-2 to Bax by immunohistochemistry.Iptakalim inhibited OGD-induced cell death in cultured neurons and astrocytes,and lactate dehydrogenase release from cerebral microvascular endothelial cells.Iptakalim reduced mRNA expression of caspase-3 and increased the ratio of Bcl-2 to Bax in NVU cells.Conclusions:Iptakalim confers neuroprotection against cerebral I/R injury by protecting NVU cells via inhibiting of apoptosis.
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 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.
文摘The neurovascular bundle of the prostate and cavernosal nerves have been used to describe the same structure ever since the publication of the first studies on the neuroanatomy of the lower urogenital tract of men, studies that were prompted by postoperative complications arising from radical prostatectomy. In urological surgery every effort is made to preserve or restore the neurovascular bundle of the prostate to avoid erectile dysfunction （ED）. However, the postoperative potency rates are yet to be satisfactory despite all advancements in radical prostatectomy technique. As the technology associated with urological surgery develops and topographical studies on neuroanatomy are cultivated, new observations seriously challenge the classical teachings on the topography of the neurovascular bundle of the prostate and the cavernosal nerves. The present review revisits the classical and most recent data on the topographical anatomy of the neurovascular bundle of the prostate prostatectomy techniques.
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Summary： Activated protein C （APC）, a natural anticoagulant, has been reported to exert direct vascu- loprotective, 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. In- traperitoneal injection of 300 ~tg/kg lipopolysaccharide （LPS） was administered consecutively to preg- nant Sprague-Dawley rats at embryonic days 19 and 20 to establish the rat model of intrauterine infec- tion-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 imme- diately after birth. Brain tissues were collected at postnatal day 7 and stained with hematoxylin and eo- sin （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 ob- served 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 acti- vated and the mRNA 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 mRNA and protein ex- pression levels were both down-regulated. Our results suggested that APC exerted neuroprotective ef- fects on multiple components of the neurovascular unit in neonatal rats with intrauterine infec- tion-induced white matter injury, and the underlying mechanisms might involve decreased expression of PAR1.
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supported by the National Key Research and Development Program of China(81930103)the National Natural Science Foundations of China(82104162)the Natural Science Foundation of Jiangsu Province(BK20210539).
文摘Epilepsy is a multifaceted neurological syndrome characterized by recurrent,spontaneous,and synchronous seizures.The pathogenesis of epilepsy,known as epileptogenesis,involves intricate changes in neurons,neuroglia,and endothelium,leading to structural and functional disorders within neurovascular units and culminating in the development of spontaneous epilepsy.Although current research on epilepsy treatments primarily centers around anti-seizure drugs,it is imperative to seek effective interventions capable of disrupting epileptogenesis.To this end,a comprehensive exploration of the changes and the molecular mechanisms underlying epileptogenesis holds the promise of identifying vital biomarkers for accurate diagnosis and potential therapeutic targets.Emphasizing early diagnosis and timely intervention is paramount,as it stands to significantly improve patient prognosis and alleviate the socioeconomic burden.In this review,we highlight the changes and molecular mechanisms of the neurovascular unit in epileptogenesis and provide a theoretical basis for identifying biomarkers and drug targets.
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 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.
文摘The objective of this study was to compare the outcomes of the modified Nesbit procedure using different techniques for dissecting the neurovascular bundle （NVB） to correct ventral congenital penile curvatures （CPCs）. The bundle was mobilized using the medial and lateral dissection technique in 21 （Group 1） and 13 （Group 2） patients, respectively. In the medial technique, Buck＇s fascia is opened at the dorsal side of the penis, the deep dorsal vein is removed at the most prominent site of the curvature and a diamond-shaped tunica albuginea （TA） is excised from the midline of the penis. In the lateral technique, the bundle is mobilized using a longitudinal lateral incision of the Buck＇s fascia above the urethra at the 5 and 7 o＇clock positions via a bilateral approach. The localization and degree of curvature was evaluated using the combined intracavernous injection stimulation test or from the patients＇ photographs. The mean patient age and degree of curvature were similar between groups. The mean operation time was longer for Group 2 （P= 0.01）. In Group 1, nine patients （42.8%） required one diamond excision, 10 （47.6%） required two diamond excisions and two （9.5%） required more than two excisions; in Group 2, six patients （46.2%） required two diamond excisions and seven patients （53.8%） required more than two diamond excisions （P = 0.019）. The differences in penile shortening, penile straightening and numbness of the glans penis were not statistically significant. Medial dissection of the bundle for the modified Nesbit procedure reduces the number of diamond-shaped removals of TA and thus shortens operation time in comparison with its lateral counterpart.
