Role of CD36 in central nervous system diseases

CD36 is a highly glycosylated integral membrane protein that belongs to the scavenger receptor class B family and regulates the pathological progress of metabolic diseases.CD36 was recently found to be widely expressed in various cell types in the nervous system,including endothelial cells,pericytes,astrocytes,and microglia.CD36 mediates a number of regulatory processes,such as endothelial dysfunction,oxidative stress,mitochondrial dysfunction,and inflammatory responses,which are involved in many central nervous system diseases,such as stroke,Alzheimer’s disease,Parkinson’s disease,and spinal cord injury.CD36 antagonists can suppress CD36 expression or prevent CD36 binding to its ligand,thereby achieving inhibition of CD36-mediated pathways or functions.Here,we reviewed the mechanisms of action of CD36 antagonists,such as Salvianolic acid B,tanshinone IIA,curcumin,sulfosuccinimidyl oleate,antioxidants,and small-molecule compounds.Moreover,we predicted the structures of binding sites between CD36 and antagonists.These sites can provide targets for more efficient and safer CD36 antagonists for the treatment of central nervous system diseases.

Mesenchymal stem cell-derived extracellular vesicles therapy in traumatic central nervous system diseases:a systematic review and meta-analysis

Although there are challenges in treating traumatic central nervous system diseases,mesenchymal stem cell-de rived extracellular vesicles(MSC-EVs) have recently proven to be a promising non-cellular the rapy.We comprehensively evaluated the efficacy of mesenchymal stem cell-de rived extracellular vesicles in traumatic central nervous system diseases in this meta-analysis based on preclinical studies.Our meta-analysis was registered at PROSPERO(CRD42022327904,May 24,2022).To fully retrieve the most relevant articles,the following databases were thoro ughly searched:PubMed,Web of Science,The Cochrane Library,and Ovid-Embase(up to April 1,2022).The included studies were preclinical studies of mesenchymal stem cell-derived extracellular vesicles for traumatic central nervous system diseases.The Systematic Review Centre for Laboratory Animal Experimentation(SYRCLE)’s risk of bias tool was used to examine the risk of publication bias in animal studies.After screening 2347studies,60 studies were included in this study.A meta-analysis was conducted for spinal co rd injury(n=52) and traumatic brain injury(n=8).The results indicated that mesenchymal stem cell-derived extracellular vesicles treatment prominently promoted motor function recovery in spinal co rd injury animals,including rat Basso,Beattie and Bresnahan locomotor rating scale scores(standardized mean difference [SMD]:2.36,95% confidence interval [CI]:1.96-2.76,P <0.01,I2=71%) and mouse Basso Mouse Scale scores(SMD=2.31,95% CI:1.57-3.04,P=0.01,I2=60%) compared with controls.Further,mesenchymal stem cell-de rived extracellular vesicles treatment significantly promoted neurological recovery in traumatic brain injury animals,including the modified N eurological Severity Score(SMD=-4.48,95% CI:-6.12 to-2.84,P <0.01,I2=79%) and Foot Fault Test(SMD=-3.26,95% CI:-4.09 to-2.42,P=0.28,I2=21%) compared with controls.Subgroup analyses showed that characteristics may be related to the therapeutic effect of mesenchymal stem cell-de rived extra cellular vesicles.For Basso,Beattie and Bresnahan locomotor rating scale scores,the efficacy of allogeneic mesenchymal stem cell-derived extracellular vesicles was higher than that of xenogeneic mesenchymal stem cell-derived extracellular vesicles(allogeneic:SMD=2.54,95% CI:2.05-3.02,P=0.0116,I2=65.5%;xenogeneic:SMD:1.78,95%CI:1.1-2.45,P=0.0116,I2=74.6%).Mesenchymal stem cellde rived extracellular vesicles separated by ultrafiltration centrifugation combined with density gradient ultra centrifugation(SMD=3.58,95% CI:2.62-4.53,P <0.0001,I2=31%) may be more effective than other EV isolation methods.For mouse Basso Mouse Scale scores,placenta-derived mesenchymal stem cell-de rived extracellular vesicles worked better than bone mesenchymal stem cell-derived extracellular vesicles(placenta:SMD=5.25,95% CI:2.45-8.06,P=0.0421,I2=0%;bone marrow:SMD=1.82,95% CI:1.23-2.41,P=0.0421,I2=0%).For modified Neurological Severity Score,bone marrow-derived MSC-EVs worked better than adipose-derived MSC-EVs(bone marrow:SMD=-4.86,95% CI:-6.66 to-3.06,P=0.0306,I2=81%;adipose:SMD=-2.37,95% CI:-3.73 to-1.01,P=0.0306,I2=0%).Intravenous administration(SMD=-5.47,95% CI:-6.98 to-3.97,P=0.0002,I2=53.3%) and dose of administration equal to 100 μg(SMD=-5.47,95% CI:-6.98 to-3.97,P <0.0001,I2=53.3%)showed better res ults than other administration routes and doses.The heterogeneity of studies was small,and sensitivity analysis also indicated stable results.Last,the methodological quality of all trials was mostly satisfactory.In conclusion,in the treatment of traumatic central nervous system diseases,mesenchymal stem cell-derived extracellular vesicles may play a crucial role in promoting motor function recovery.

Research progress of sphingosine 1-phosphate and its signal transduction in central nervous system diseases

Sphingosine 1-phosphate(S1P),as a sphingolipid metabolite,has become a key substance in regulating various physiological processes,involved in differentiation,proliferation,migration,morphogenesis,cytoskeleton formation,adhesion,apoptosis,etc.process.Sphingosine 1-phosphate can not only activate the S1P-S1PR signaling pathway by binding to the corresponding receptors on the cell membrane,but also play a role in the cell.In recent years,studies have found that there is a certain relationship between its level changes and the occurrence and development of central nervous system diseases.This article reviews the latest knowledge of sphingosine-1-phosphate in the occurrence and treatment of nervous system diseases,and further clarifies its molecular mechanism in the treatment and development of central nervous system diseases.

Heterogeneity of mature oligodendrocytes in the central nervous system

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.

Single-atom nanozymes towards central nervous system diseases

Nanozymes have a similar catalytic mechanism to natural enzymes,with excellent performance,facile synthesis,and better stability.Single-atom nanozymes are developed based on single-atom catalysts due to their advantages in coordination structure and electronic configuration,making them highly enzymatic-like biomimetic catalysts.Central nervous system(CNS)diseases have become one of the biggest killers of human health because they are difficult to diagnose and treat,expensive,and result in serious illness.Single-atom nanozymes have been widely used for biomedical applications,especially in oxidative-stressinduced diseases and most CNS diseases which are closely related to oxidative stress.Therefore,single-atom nanozymes show promising application prospects for the treatment of CNS diseases.In addition,due to the outstanding material properties and sensitivity of single-atom nanozymes,they also exhibit great advantages in detecting various CNS disease markers for diagnosis.

Connexin:a potential novel target for protecting the central nervous system?

Connexin subunits are proteins that form gap junction channels, and play an important role in communication between adjacent cells. This review article discusses the function of connexins/hemichannels/gap junctions under physiological conditions, and summarizes the findings re-garding the role of connexins/hemichannels/gap junctions in the physiological and pathological mechanisms underlying central nervous system diseases such as brain ischemia, traumatic brain and spinal cord injury, epilepsy, brain and spinal cord tumor, migraine, neuroautoimmune disease, Alzheimer’s disease, Parkinson’s disease, X-linked Charcot-Marie-Tooth disease, Peli-zaeus-Merzbacher-like disease, spastic paraplegia and maxillofacial dysplasia. Connexins are considered to be a potential novel target for protecting the central nervous system.

Current application and future directions of photobiomodulation in central nervous diseases

Photobiomodulation using light in the red or near-infrared region is an innovative treatment strategy for a wide range of neurological and psychological conditions.Photobiomodulation can promote neurogenesis and elicit anti-apoptotic,antiinflammatory and antioxidative responses.Its therapeutic effects have been demonstrated in studies on neurological diseases,peripheral nerve injuries,pain relief and wound healing.We conducted a comprehensive literature review of the application of photobiomodulation in patients with central nervous system diseases in February 2019.The NCBI PubMed database,EMBASE database,Cochrane Library and ScienceDirect database were searched.We reviewed 95 papers and analyzed.Photobiomodulation has wide applicability in the treatment of stroke,traumatic brain injury,Parkinson’s disease,Alzheimer’s disease,major depressive disorder,and other diseases.Our analysis provides preliminary evidence that PBM is an effective therapeutic tool for the treatment of central nervous system diseases.However,additional studies with adequate sample size are needed to optimize treatment parameters.

The Clinical Application Value of Susceptibility Weighted Imaging in the Central Nervous System

Susceptibility weighted imaging(SWI)is a relatively new magnetic resonance imaging(MRI)technique that uses the difference in tissue magnetic susceptibility to image,and has unique value compared to traditional magnetic resonance imaging.This article summarizes its application in the central nervous system and provides a reference for imaging diagnosis and clinical treatment.

Review on the Effect of Resveratrol on Central Nervous System Disease

Resveratrol (3,5,4’-trihydroxy-trans-stilbene, RV) is a kind of phytoalexin found in many kinds of plants and food. As a natural antioxidant, RV shows significant biological activity, including anti-tumor activity, antitubulin activity, cardiovascular disease resistance activity, etc. Many experiments confirm that resveratrol displays a wide range of beneficial effects on human diseases including heart disease and cancer, especially in the treatment of central nervous system disease, such as Huntington’s disease (HD), Alzheimer’s disease (AD) and Parkinson’s disease (PD). This paper summarizes the positive effects of RV on several central nervous system diseases.

Global trends of fMRI studies on acupuncture for CNS diseases over the past two decades:A bibliometric analysis

Background:Extensive global research has been conducted to explore the neural mechanisms involved in acupuncture treatment for central nervous system(CNS)disorders.However,there is a lack of bibliometric analysis specifically focusing on functional magnetic resonance imaging(fMRI)studies examining the effects of acupuncture on CNS diseases.Objective:This study aims to fill this gap by offering a theoretical framework for the current clinical application and future research directions.It presents a comprehensive overview of the current state,hotspots,and global trends in fMRI studies on therapeutic applications and potential mechanisms of acupuncture for CNS diseases over the past two decades.Methods:The publications were analyzed using VOSviewer 1.6.18 and CiteSpace 6.1.R6 software running on the Java platform.All publications were acquired from the Science Citation Index-Expanded of the Web of Science Core Collection.The document types were limited to original articles and review articles,with publication dates spanning from October 24,2003 to October 24,2023.Only publications written in the English language were considered for analysis.Results:fMRI has the advantages of non-invasiveness,high spatial resolution,and signals directly from neural activity in the brain.Compared to the other three brain imaging techniques,fMRI has the most significant articles on acupuncture treatment for CNS diseases in the past two decades,with a substantial increase.As of October 24,2023,227 records of fMRI studies on acupuncture for CNS diseases were identified.Notably,a discernible upward trend exists in this domain’s overall number of annual publications.It is worth highlighting that China has emerged as the primary contributor to this field.The five most prominent topics explored in fMRI studies on acupuncture for CNS diseases encompassed the concepts of"acupuncture""fMRI""electroacupuncture""functional connectivity"and"stimulation".Furthermore,the frontier areas of investigation encompassed the topics of"migraine without aura""ischemic stroke""prophylaxis"and"randomized controlled trial".Conclusion:fMRI studies on acupuncture treatment in CNS diseases have potential applications,and the number of publications on this topic is expected to increase rapidly in future research,which may focus on migraine without aura,ischemic stroke,and randomized controlled trials.fMRI studies of acupuncture for CNS diseases have connected various brain areas,focusing on the default mode network.In addition,strengthening collaboration among different academic groups across countries is imperative.

Non-glaucomatous peripapillary retinal nerve fiber layer defect

Retinal nerve fiber layer （RNFL）, which originates from various locations of the retina and converge toform the optic nerve, makes up the innermost neural layer of the retina~ RNFL defect, including localized and diffuse RNFL defect, is believed to be a characteristic feature of glaucoma and an important clue for the detection of early glaucoma, which may precede detectable optic disc changes and visual field loss. However, RNFL defect does not always equate to a diagnosis of glaucoma, and it can also be induced by vascular accidents or some other events in RNFL1, suc as hypertension, non-arteritic anterior ischemic optic neuropathy, multiple sclerosis, and so on.