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The function of the central nervous system was significantly altered under high-altitude hypoxia, and these changes lead to central nervous system disease and affected the metabolism of drugs in vivo. The blood-brain barrier is essential for maintaining central nervous system stability and plays a key role in the regulation of drug metabolism, and barrier structure and dysfunction affect drug transport to the brain. Changes in the structure and function of the blood-brain barrier and the transport of drugs across the blood-brain barrier under high-altitude hypoxia are regulated by changes in brain microvascular endothelial cells, astrocytes and pericytes, and are regulated by drug metabolism factors such as drug transporters and drug metabolizing enzymes. This article reviews the effects of high-altitude hypoxia on the structure and function of the blood-brain barrier and the effects of changes in the blood-brain barrier on drug metabolism. We investigate the regulatory effects and underlying mechanisms of the blood-brain barrier and related pathways such as transcription factors, inflammatory factors and nuclear receptors on drug transport under high-altitude hypoxia.
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Alzheimer’s disease (AD) is a common chronic neurodegenerative disease (ND) that is mainly investigated nowadays because of its increased incidence and burden on the elderly population. It leads to atrophy of the brain. Clinical features of AD include loss of memory with impaired cognition and behaviour, which leads to mood instability and death. Aggregation of beta-amyloid protein(A?) and neurofibrillary tangles within the neuronal cells are the accepted pathophysiological process of AD. Studies have demonstrated that medicinal plants and herbs could improve memory and cognitive function affected by AD. The bioavailability of active herbal components is affected by rapid metabolism, less permeability, and decreased stability within the CNS. Many studies have reported that the application of nanotechnology to plant extracts enhances the efficacy of extracts. Adding herbal extracts into the nanoparticle system could improve the action of extracts, promote the sustained release of bioactive components, decrease the required dose, and lower the side effects. Using published articles from trustworthy resources like PubMed, Google Scholar, Research Gate, Web of Science, and Wiley Online Library, with keywords like "natural products," "Alzheimer's disease," and "nanotechnology," herein we reviewed and summarized recent nano-drug delivery treatment strategies for AD using natural products.
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RESUMEN Introducción: La tripanosomiasis africana humana es producida por protozoos del género Trypanosoma y transmitida fundamentalmente por la picadura de la mosca tse-tsé. En el último siglo ha habido varias epidemias en el África, pero dado que el número de nuevos casos notificados había disminuido, la hoja de ruta de la OMS para las enfermedades tropicales desatendidas fijó el objetivo de su eliminación como problema de salud pública para 2020. Muchos de los países donde Cuba presta colaboración internacionalista son endémicos, por lo que los colaboradores están expuestos al riesgo de padecer y enfrentar esta enfermedad. Objetivo: Realizar una actualización clínica y epidemiológica de la entidad para alertar sobre la posibilidad de la aparición en áreas endémicas y la presencia de casos importados en Cuba. Métodos: Se realizó una revisión bibliográfica en la base de datos Medline/PubMed y en artículos relevantes relacionados con el tema, de los últimos años; también hemos tomado como referencia las notas descriptivas de tripanosomiasis africana de la OMS en el 2020, así como textos clásicos de medicina interna y la plataforma búsqueda ClinicalKey. Información, análisis y síntesis: Se hizo una detallada exposición de la enfermedad y la conducta terapéutica; una breve reseña de los casos importados y del país de procedencia, además del peligro que presenta la aparición de casos importados para Cuba. Conclusiones: La enfermedad es una entidad potencialmente mortal, endémica en países donde existe colaboración cubana. Es necesario tener presente el diagnóstico de esta enfermedad para un abordaje terapéutico adecuado.
ABSTRACT Introduction: Human African trypanosomiasis is produced by protozoa of the genus Trypanosoma and transmitted mainly by the bite of the tsetse fly. There have been several epidemics in Africa in the last century, but as the number of new reported trypanosomiasis cases has decreased, the WHO roadmap for neglected tropical diseases had targeted their elimination as a public health problem by 2020. Many of the countries where Cuba provides internationalist collaboration are endemic, so the collaborators are exposed to the risk of suffering and facing this disease. Objectives: To carry out a clinical and epidemiological update of the entity and warn about the possibility of the appearance in endemic areas and the presence of imported cases in Cuba. Methods: a bibliographic review was carried out in the Medline / Pub Med database and in relevant articles related to the subject, from recent years; we have taken the 2020 WHO African Trypanosomiasis descriptive notes as a reference, as well as classic internal medicine texts and the ClinicalKey search platform. Information, Analysis and Synthesis: A detailed exposition of the disease and the therapeutic behavior was made; a brief review of imported cases and the country of origin, in addition to the danger posed by the appearance of imported cases for Cuba. Conclusions: This is a potentially fatal entity, endemic in countries where there is Cuban collaboration. It is necessary to bear in mind the diagnosis of this disease for an adequate therapeutic approach.
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Objective:To explore the effect of hyperbaric oxygen (HBO) on the blood-brain barrier via the silent information regulator 1 (SIRT1)/Forkhead box O1(FoxO1) signaling pathway after cerebral ischemia and reperfusion using a rat model.Methods:Forty Wistar rats were randomly assigned into sham, cerebral ischemia-reperfusion (CIR), CIR+ HBO and CIR+ HBO+ EX527 groups, each of 10. The cerebral ischemia-reperfusion model was established in all groups except the sham group by right middle cerebral artery occlusion using the modified thread-occlusion method. The sham group was not ligated. Both the CIR+ HBO and CIR+ HBO+ EX527 groups were given HBO 1, 9, 21, 45 and 69 hours after the reperfusion. The CIR+ HBO+ EX527 group was additionally injected with 5mg/kg of EX527(a SIRT1inhibitor) peritoneally 4, 12, 24, 48 and 72 hours after the reperfusion. Then 2% Evens blue (EB) was injected into the tail vein an hour before the rats were sacrificed. The content of EB and the expression of SIRT1, FoxO1, ZO-1, Occludin, Claudin-5 mRNA and their proteins were determined using spectrophotometry, reverse transcription-polymerase chain reactions and Western blotting.Results:The average EB content of the hippocampal brain tissue from the CIR, CIR+ HBO and CIR+ HBO+ EX527 rats was significantly greater than the Sham group′s average 72h after reperfusion. The average expression of SIRT1, FoxO1, ZO-1, Occludin and Claudin-5 mRNA and their proteins was significantly lower, with the CIR + HBO + EX 527 group′s average significantly lower than that of the CIR+ HBO group.Conclusions:HBO can increase the expression of tight junction protein via the SIRT1/FoxO1 pathway. It helps to protect the blood-brain barrier in CIR injury situations.
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Multiple sclerosis (MS) is an idiopathic inflammatory demyelinating diseases of the central nervous system, the underlying cause of which has not been cleared. Previous studies have shown that the pathogenesis of MS is related to the destruction of blood brain barrier, furthermore the drugs used to treat MS have a certain protective effect on the function of blood brain barrier. Therefore, this review combines the research progress at home and abroad to clarify the relationship between the blood brain barrier and MS in pathogenesis and treatment, proposing possible orientation of development.
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Dementia with Lewy bodies(DLB)is the second most common neurodegenerative dementia after Alzheimer's Disease(AD). This article will mainly elaborate the relationship between DLB and blood-brain barrier(BBB)from the following five aspects: (1)The structure and function of BBB; (2)In vivo assessment methods for the blood-brain barrier damage; (3)Evidence for the damage of blood-brain barrier in DLB; (4)The relationship between α-synuclein and the blood-brain barrier; (5)The relationship between APOE and the blood-brain barrier.Future research should focus on the pathogenesis of BBB damage in DLB patients, by which new drug targets for disease diagnosis and treatment may be found.
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OBJECTIVE To study the impr ovement effects of Dianxianqing granule on blood-brain barrier （BBB）injury in Alzheimer’s disease （AD）model mice by regulating NLR family pyrin domain containing 3（NLRP3）inflammasome signaling pathway. METHODS Totally 125 mice were randomly divided into sham operation group （n＝25）and modeling group （n＝100） by body weight. AD model was induced by intracerebroventricular injection of β-amyloid 25-35 in model group. Sham operation group was given normal saline with same method. The 100 model mice were randomly divided into model group ，Donepezil hydrochloride tablets group （positive control 1，1.3 mg/kg，i.g.），MCC950 group [positive control 2（selective NLRP 3 inhibitor），10 mg/kg，i.p.] and Dianxianqing granule group （12.48 g/kg by crude drug ，i.g.）by body weight ，with 25 mice in each group. Second day after modeling ，administration groups were given relevant medicine ，once a day ，for consecutive 21 d. Sham operation group and model group were given intragastric administration of water and intraperitoneal injection of normal saline. At last administration，the learning and memory ability was determined by Y maze test ，and blood-brain barrier permeability was measured by Evans blue leakage assay. The expressions of NLRP 3，anti-ionized calcium-binding adapter molecule 1（IBA-1），nuclear factor kappa B （NF-κB）p65，p53 upregulated modulator of apoptosis （PUMA），occludin（ocln），zonula occluden- 1（ZO-1）and claudin-5 （cldn5） in cerebral tissue were determined. RESULTS Compared with model group ， spontaneous alternate response rate ，protein expressions of ocln ，cldn5 lnzyxyqy2003@163.com and ZO- 1 in cerebral tissue were increased significantly in administration groups （P＜0.05 or P＜0.01）；Evans blue E-mail：jiadg2003@126.com content and protein expressions of NLRP 3，IBA-1，PUMA and NF-κB p65 in cerebral tissue were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Dianxianqing granule can improve BBB injury of AD model m ice by inhibiting NLRP 3 inflammasome signaling pathway.
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@#Objective To observe the effect of hyperbaric oxygen chamber treatment on the expression of autophagy protein microtubule associated protein 1 light chain 3 (LC3) and Beclin-1 in cerebral vascular endothelial cells of rats with ischemia-reperfusion injury, and to explore the mechanism of hyperbaric oxygen in repairing blood-brain barrier in rats with ischemia-reperfusion injury.Methods A total of 54 Sprague-Dawley rats were randomly divided into sham operated group (n=12), cerebral ischemia-reperfusion injury (CIRI) model group (n=18), hyperbaric oxygen group (n=12) and inhibitor group (n=12). The CIRI model was made by a suture method in the model group, hyperbaric oxygen group and inhibitor group. The hyperbaric oxygen group and inhibitor group accepted hyperbaric oxygen, and the inhibitor group injected 3-methyladenine in lateral cerebral ventricle before treatment. They were stained with Evans blue and Evans blue content in the infarct area was detected 72 hours after CIRI. Double immunofluorescent staining was used to observe the expression of LC3 in vascular endothelial cells marked with CD31 in the model group, and LC3-II and Beclin-1 in infarcted cortical microvascular were examined by Western blotting in all the groups.Results Compared with the sham operation group, Evans blue content in the infarct area was significantly higher in the model group (P<0.01); compared with the model group, the content of Evans blue in the infarct area decreased significantly in hyperbaric oxygen group (P<0.01); compared with the hyperbaric oxygen group, the content of Evans blue in the infarct area was significantly higher in the inhibitor group (P < 0.05). There was obvious expression of LC3 in CD31+ cells. The expression levels of Beclin-1 and LC3-Ⅱ in the infarcted area were significantly higher in the model groupt than in the sham operation group (P<0.01); and it was significantly higher in the hyperbaric oxygen group than in the model group (P<0.05) and was lower in the inhibitor group than in the hyperbaric oxygen group and model group (P < 0.01).Conclusion Autophagy exists in vascular endothelial cells in the injured area of rats with CIRI. Hyperbaric oxygen can upregulate the expression of autophagy proteins LC3-Ⅱ and Beclin-1 in vascular endothelial cells in the infarcted area, to promote repairing blood-brain barrier.
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@#As a structural barrier between the brain and the systemic circulation, the blood-brain barrier prevents macromolecules and most small-molecule drugs from entering the brain, which make it difficuct to treat central diseases.Various solute carriers such as glucose transporters and amino acid transporters which can transport various nutrients into the brain, are highly expressed on the blood-brain barrier.The ligand corresponding to the transporter is modified on the nano-drug carrier, and the drug is carried across the blood-brain barrier through transporter-mediated transport, which can achieve high-efficiency delivery of drugs to the brain and improve the diagnostic sensitivity and therapeutic effect of central diseases.In this paper, we review different types of solute carriers to mediate nanoformulations such as liposomes, metal nanoparticles, polymer micelles and dendrimers across the blood-brain barrier for the treatment of brain diseases and discuss the opportunities and challenges of this strategy in future applications.
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A blood-brain barrier microfluidic chip platform for studying the permeability of active components in traditional Chinese medicine was developed. This model used primary human brain microvascular endothelial cells on a microfluidic chip consisting of two perpendicularly-crossing channels and a single layer porous polycarbonate membrane. The physiological shear stress in the human vasculature was also modeled in this device. Cell viability on the chip was monitored by cell staining and immunofluorescence staining. The cells spread well and the structure of an intercellular adhesion protein was satisfactory. The permeability of fluorescent tracers and three model drugs and the functional expression of P-glycoprotein (P-gp)on the blood-brain barrier were investigated. The results show that the apparent permeability coefficients (Papp) of the fluorescent tracers and three model drugs were consistent with those reported in the literature, and P-gp on the chip showed normal function, indicating that there was a complete structure and a functional BBB. The permeability of six active components of traditional Chinese medicine was investigated through this microfluidic chip and the drug concentration was determined by HPLC-MS/MS to obtain the Papp of each component. The Papp of corydaline was (4.51 ± 1.90)×10-7 cm·s-1, the Papp of tetrahydropalmatine was (9.10 ± 6.59)×10-7 cm·s-1, and the Papp of imperatorin was (9.38 ± 2.53)×10-7 cm·s-1; the concentration of isoimperatorin, baicalin and chlorogenic acid was below the limit of quantification, which suggested that isoimperatorin, baicalin and chlorogenic acid have poor permeability in this BBB chip. This blood-brain barrier microfluidic platform possesses a complete barrier function and near-physiological conditions and could be a valuable in vitro tool for drug permeability evaluation.
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Brain-targeted delivery plays an important role in the diagnosis and treatment of neurological diseases, but the existence of blood brain barrier (BBB) limits the development of brain-targeted delivery. As cell-derived nanovesicles, exosomes can participate in the transportation of substances between cells to mediate the communication between cells to play a biological regulatory role in vivo. Due to the low immunogenicity, low toxicity, high engineering and natural crossing over BBB, exosomes play an important role in brain-targeted delivery. In this paper, the composition of exosomes, the mechanism of brain targeted delivery and its role in various brain diseases are systematically described.
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ObjectiveTo observe the protective effect of Sanhuatang and its modifications on the brain tissue of rats exposed to cerebral ischemia-reperfusion injury （CIRI） and explore its action mechanism and compatibility characteristics. MethodOne hundred and forty SD male rats of clean grade were randomly divided into the control group， sham-operation group， and operation group. The Longa suture method was employed to establish the CIRI model. The successfully modeled CIRI rats were further divided into five groups， namely the model group， nimodipine group， Sanhuatang without Notopterygii Rhizoma et Radix group， Notopterygii Rhizoma et Radix group， and Sanhuatang group， and treated with the corresponding medicines by gavage for five days. The cerebral infarct size in each group was examined by 2，3，5-triphenyltetrazolium chloride （TTC） staining， and the pathological changes in the brain tissue were observed by hematoxylin-eosin （HE） staining and electron microscopy. The mRNA and protein expression levels of Claudin-5， Occludin， and zonula occludens-1 （ZO-1） in brain tissues were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the control group， the model group exhibited markedly increased infarct size， obvious changes in brain morphology and ultrastructure， and down-regulated mRNA and protein expression of Claudin-5， Occludin， and ZO-1 （P<0.01）. Compared with the model group， both nimodipine and Sanhuatang significantly decreased the infarct size （P<0.01） and relived the pathological changes. The infarct sizes in the Sanhuatang without Notopterygii Rhizoma et Radix group and Notopterygii Rhizoma et Radix group were reduced without exhibiting a statistically significant difference. The mRNA and protein expression levels of Claudin-5， Occludin， and ZO-1 in the nimodipine group， Sanhuatang group， and Notopterygii Rhizoma et Radix group were up-regulated significantly in comparison with those in the model group （P<0.01， P<0.01）. The mRNA and protein expression levels of Claudin-5 and ZO-1 were higher in the Notopterygii Rhizoma et Radix group than in the Sanhuatang without Notopterygii Rhizoma et Radix group （P<0.01， P<0.01）. ConclusionSanhuatang exerts the protective effect against CIRI in rats possibly by regulating the expression of Claudin-5， Occludin， and ZO-1 and improving the blood-brain barrier function. Notopterygii Rhizoma et Radix in Sanhuatang may play an important role in the protection of rats from CIRI.
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ObjectiveTo explore the therapeutic effect and mechanism of Huangqi Chifengtang on middle cerebral artery embolism（MCAO） rat model. MethodThe 90 SPF male rats were randomly divided into sham operation group， model group， high， medium and low dose groups of Huangqi Chifengtang （8.10，4.05，2.025 g·kg-1） and positive drug group （Naoxintong 0.32 g·kg-1）. MCAO rat model was established and intervened with Huangqi Chifengtang， and the neurological scores of each group were scored. The area of cerebral infarction was calculated by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Serum interleukin-6 （IL-6） and interleukin-1β（IL-1β） were detected by enzyme-linked immunosorbent assay （ELISA），The contents of matrix metalloproteinase-9（MMP-9）， vascular endothelial growth factor（VEGF） and vascular endothelial growth factor receptor 2 （VEGFR2）， the pathological changes of brain tissue in each group were observed by hematoxylin eosin （HE） staining. Western blot was used to detect zonule atresia protein-1（ZO-1）， tight junction protein-5（Claudin-5） and P-glycoprotein （P-gp） and multidrug resistance protein 1（MRP1）. ResultCompared with the sham operation group， the neurological function score and cerebral infarction rate of the model group were significantly increased（P<0.01）， and the levels of IL-6， IL-1β and MMP-9 in serum were significantly increased（P<0.01）， the levels of ZO-1 and Claudin-5 protein expression decreased significantly（P<0.01）， and the levels of P-gp and MRP1 protein expression increased significantly（P<0.01）. Compared with the model group， the neurological function score of rats in each administration group decreased significantly at 14 days （P<0.05，P<0.01）， the pathological changes of brain tissue effectively improved， the rate of cerebral infarction significantly reduced （P<0.01）， and the expression level of IL-6， IL-1β and MMP-9 in serum decreased significantly （P<0.05，P<0.01）， the content of VEGFR2 increased significantly （P<0.01）， and the content of VEGF increased significantly in high， medium dose and positive drug groups （P<0.05，P<0.01）. Although it decreased in low dose group， there was no significant difference. The levels of ZO-1 and Claudin-5 protein expression in brain tissue of high dose group and positive drug group increased significantly （P<0.05，P<0.01）， the level of MRP1 and P-gp protein expression decreased significantly （P<0.05）. ConclusionHuangqi Chifengtang can play a therapeutic role in rats with cerebral infarction by improving the pathological changes of brain tissue， reducing inflammatory reaction， promote angiogenesis and regulating the function of blood-brain barrier（BBB）.
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ObjectiveTo observe the effect of Linggui Zhugantang （LG） on the blood-brain barrier （BBB） model of Alzheimer's disease （AD） in vitro and to explore the mechanism of LG in repairing the BBB injury in AD. MethodA total of 50 male SPF rats were randomized into five groups： high-dose （4.8 g·kg-1）， medium-dose （2.4 g·kg-1）， and low-dose （1.2 g·kg-1） LG groups， western medicine （0.5 g·kg-1 donepezil hydrochloride） group， and normal group （normal saline of equivalent volume）. They received （ig） corresponding drugs twice a day for 7 d. Drug-containing serum was respectively collected from the abdominal aorta 1 h after the last administration. The BBB injury of AD in vitro was induced with the cell co-culture method， and 6 groups were designed： normal group， model group， high-， medium-， and low-dose LG groups， and western medicine group. The model group was added with 100 μL amyloid β1-42 （Aβ1-42， final concentration： 5 μmol·L-1）， and high-dose， medium-dose， and low-dose LG groups and the western medicine group were added with corresponding 10% drug-containing serum in addition to the 100 μL Aβ1-42 （final concentration： 5 μmol·L-1）. Cell survival rate was detected by methyl thiazolyl tetrazolium （MTT） assay， expression of BBB-related skeleton proteins （claudin-5， ZO-1， occludin）， matrix metalloproteinase-2 （MMP-2）， and matrix metalloproteinase-9 （MMP-9） by Western blot， and content of inflammatory factors interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） by enzyme-linked immunosorbent assay （ELISA）. BBB Aβ transporter low-density lipoprotein receptor-related protein 1 （LRP-1） and advanced glycation end product receptor （RAGE） at different time points in high-dose， medium-dose， and low-dose LG groups were determined by Real-time PCR and Western blot. ResultCell survival rate of the model group was lower than that of the normal group （P<0.05） and the survival rates of the western medicine group and high-dose LG group was higher than that in the model group （P<0.05）. The skeleton proteins were down-regulated and MMP-2 and MMP-9 were up-regulated in the model group compared with those in the normal group （P<0.05）. The expression of skeleton proteins was higher （P<0.05） and that of MMP-2 and MMP-9 was lower （P<0.05） in the western medicine group and high-dose LG group than in the model group. Compared with the model group， only the medium-dose LG group showed the up-regulation （P<0.05） of claudin-5 （P<0.05） and the decrease （P<0.05） of MMP-2. IL-1β， IL-6， and TNF-α in the model group were up-regulated （P<0.05） compared with those in the normal group， and those inflammatory factors in the western medicine group and high-dose and medium-dose LG groups were lower （P<0.05） than those in the model group. LRP-1 expression was up-regulated and RAGE expression was down-regulated at 3 h compared with those at 0 h （P<0.05）， while the expression of the two became stable at 6， 12， 24， 36 h. At 3 h， LRP-1 expression was down-regulated and RAGE expression was up-regulated in model group compared with those in the normal group at 3 h （P<0.05）. Moreover， the LRP-1 content was higher and RAGE content was lower in the western medicine group and high-dose LG group than in the model group. ConclusionLG can repair the BBB injury in vitro by inhibiting the expression of inflammatory factors and MMP-2， MMP-9， promoting the expression of skeletal proteins， and regulating the balance of transporters.
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In different stages of the course of intracerebral hemorrhage, various interleukins (ILs) play different roles. IL-1α and IL-1β can aggravate perihematomal edema (PHE) by affecting the integrity of the blood-brain barrier in the early stage of intracerebral hemorrhage. IL-6 and IL-8 play a key role in the whole course of intracerebral hemorrhage and affect the severity of PHE by inducing inflammation. IL-3 promotes the development of PHE by promoting microglia activation. IL-11 and IL-17A can be used to assess disease severity and as predictors of PHE, but they do not play a decisive role in the development of intracerebral hemorrhage. IL-4 and IL-10 have certain improvement effects on the development of PHE and the outcomes after cerebral hemorrhage.
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Cerebral small vessel disease (CSVD) is a common cerebrovascular disease in clinical practice. Its onset is hidden and its clinical manifestations are diverse. Studies have shown that there are pleiotropic effects and recurrent activation phenomenon between the functional imbalance of neurovascular unit (NVU) and a series of pathophysiological processes, such as vascular endothelial dysfunction, blood-brain barrier permeability change and glial cell activation, which jointly promote the progress of CSVD under the action of inflammatory and immune factors. This article reviews the role of NVU in the occurrence and development of CSVD.
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@#In order to investigate the effects of neuroprotective peptide SNP-9 which is derived from silk fibroin hydrolysate on the injury of the blood-brain barrier in Alzheimer′s disease (AD), Aβ25-35 was used to damage brain microvascular endothelial cells bEnd.3 to establish AD injury model and drug intervention was performed.MTT assay was used to detect the effects of SNP-9 and Aβ25-35 on cell viability.RT-qPCR was used to determine the effects of SNP-9 and Aβ25-35 on the mRNA levels of tight junctions (TJs)-related ZO-1, occludin and claudin-5.Western blot was used to detect the effects of SNP-9 and Aβ25-35 on the protein levels of TNF-α, phosphorylated NF-κB, NF-κB, IκBα and RAGE.The results showed that SNP-9 reduced bEnd.3 cell damage induced by Aβ25-35, and improved the abnormal mRNA levels of ZO-1, occludin and claudin-5 in model cells.It alleviated the abnormal protein levels of TNF-α, phosphorylated NF-κB, IκBα and RAGE induced by Aβ25-35. These results suggest that SNP-9 may regulate the levels of TNF-α in model cells by influencing RAGE/NF-κB pathway, and then ameliorate TJs-related abnormalities and alleviate bEnd.3 cell injury induced by Aβ25-35.
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Due to the special physiological and pathological characteristics of gliomas, most therapeutic drugs are prevented from entering the brain. To improve the poor prognosis of existing therapies, researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy. Although these strategies can be used clinically to overcome the blood‒brain barrier (BBB), the accurate delivery of drugs to the glioma lesions cannot be ensured. Nano-drug delivery systems (NDDS) have been widely used for precise drug delivery. In recent years, researchers have gathered their wisdom to overcome barriers, so many well-designed NDDS have performed prominently in preclinical studies. These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions, drug release in response to the glioma microenvironment, biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein, and carriers created according to the active ingredients of traditional Chinese medicines. We reviewed these well-designed NDDS in detail. Furthermore, we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy, and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.
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Microglia are the main innate immune cells in the central nervous system, which play a variety of roles in the development of the central nervous system and the occurrence of diseases. Recent studies have found that microglia play an important role in the occurrence and development of vascular cognitive impairment (VCI), which can lead to cognitive decline by activating neuroinflammation, oxidative stress, and destroying the blood-brain barrier. This article reviews the role of microglia in the pathophysiology of VCI, aiming to provide a new basis for targeting microglia to treat VCI.
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Cerebral small vessel disease (CSVD) is a common and slowly progressive cerebrovascular disease. Its pathological mechanism involves vascular endothelial dysfunction, blood-brain barrier destruction, neuronal apoptosis, glial cell activation, and inflammatory reaction. Neurovascular unit is the basic unit of brain structure and function, and its pathological changes are closely associated with many cerebrovascular diseases. At present, the damage mechanism of neurovascular unit in CSVD has been paid more and more attention. This article reviews the damage mechanism of neurovascular unit in CSVD.