BACKGROUND The diagnostic value of metagenomic next-generation sequencing(mNGS)in central nervous system(CNS)infectious diseases after empirical treatment has not been reported.AIM To investigate the diagnostic value ...BACKGROUND The diagnostic value of metagenomic next-generation sequencing(mNGS)in central nervous system(CNS)infectious diseases after empirical treatment has not been reported.AIM To investigate the diagnostic value of mNGS of cerebrospinal fluid(CSF)in the empirically treated CNS infectious diseases.METHODS A total of 262 CSF samples from patients with suspected CNS infections were collected between August 2020 and December 2021.Both mNGS and conventional methods were used for testing.The conventional methods included microbial culture,smear,polymerase chain reaction,etc.RESULTS Among 262 suspected cases,183 cases(69.84%)were diagnosed as CNS infection,including 86 cases of virus infection(47.00%),70 cases of bacterial infection(38.25%)and 27 cases of fungal infection(14.76%).The sensitivity and specificity of mNGS were 65.6%(95%CI:58.2%-72.3%)and 89.6%(95%CI:79.1%-95.3%),respectively.The PPV of mNGS was 94.5%(95%CI:88.6%-97.6%),and the NPV was 48.8%(95%CI:39.7%–57.9%).The pathogen detective sensitivity and accuracy of mNGS were higher than those of conventional methods(Sensitivity:65.6%vs 37.2%;P<0.001;Accuracy:72.0%vs 50%,P<0.001).The results showed that compared with conventional methods,mNGS technology was a more sensitive method for the diagnosis of CNS infection after empirical treatment.CONCLUSION mNGS can be a better method applied in the diagnosis of CNS infection after empirical treatment.展开更多
The present study analyzed the anatomical association between intracranial subarachnoid space and the cervical lymphatic system. X-ray contrast medium and Microfil (Microfil compounds fill and opacify microvascular a...The present study analyzed the anatomical association between intracranial subarachnoid space and the cervical lymphatic system. X-ray contrast medium and Microfil (Microfil compounds fill and opacify microvascular and other spaces of non-surviving animals and post-mortem tissue under physiological injection pressure) were injected into the cisterna magna of the rabbit, and perineural routes of cerebrospinal fluid outflow into the lymphatic system were visualized. Under a surgical operating microscope, Microfil was found within the subarachnoid space and along the olfactory nerves. At the nasal mucosa, a lymphatic network was identified near the olfactory nerves, which crossed the nasopharyngeal region and finally emptied into the superficial and deep cervical lymph nodes. Under a light microscope, Microfil was visible around the olfactory nerves and within lymphatic vessels. These results suggested that cerebrospinal fluid drained from the subarachnoid space along the olfactory nerves to nasal lymphatic vessels, which in turn, emptied into the cervical lymph nodes. This anatomical route, therefore, allowed connection between the central nervous system and the lymphatic system.展开更多
As the key producer of cerebrospinal fluid(CSF),the choroid plexus(CP) provides a unique protective system in the central nervous system.CSF components are not invariable and they can change based on the pathologi...As the key producer of cerebrospinal fluid(CSF),the choroid plexus(CP) provides a unique protective system in the central nervous system.CSF components are not invariable and they can change based on the pathological conditions of the central nervous system.The purpose of the present study was to assess the effects of non-traumatic and traumatic CSF on the differentiation of multipotent stem-like cells of CP into the neural and/or glial cells.CP epithelial cells were isolated from adult male rats and treated with human non-traumatic and traumatic CSF.Alterations in m RNA expression of Nestin and microtubule-associated protein(MAP2),as the specific markers of neurogenesis,and astrocyte marker glial fibrillary acidic protein(GFAP) in cultured CP epithelial cells were evaluated using quantitative real-time PCR.The data revealed that treatment with CSF(non-traumatic and traumatic) led to increase in m RNA expression levels of MAP2 and GFAP.Moreover,the expression of Nestin decreased in CP epithelial cells treated with non-traumatic CSF,while treatment with traumatic CSF significantly increased its m RNA level compared to the cells cultured only in DMEM/F12 as control.It seems that CP epithelial cells contain multipotent stem-like cells which are inducible under pathological conditions including exposure to traumatic CSF because of its compositions.展开更多
Superficial siderosis of the central nervous system (SSCNS) is usually caused by chronic subarachnoid hemorrhage which leads to the accumulation of hemosiderin in the subpial layers of the brain and the spinal cord. T...Superficial siderosis of the central nervous system (SSCNS) is usually caused by chronic subarachnoid hemorrhage which leads to the accumulation of hemosiderin in the subpial layers of the brain and the spinal cord. The exact clinical manifestations and T2-weighted magnetic resonance imaging (MRI) the patient presented here is diagnosed SSCNS mainly due to the cytology of cerebrospinal fluid (CCSF) and the superficial siderosis of T2-weighted MRI. CCSF can be a good complementary to the diagnosis of SSCNS.展开更多
The glymphatic system is a relatively recently identified fluid exchange and transpo rt system in the brain.Accumulating evidence indicates thatglymphatic function is impaired not only in central nervous system disord...The glymphatic system is a relatively recently identified fluid exchange and transpo rt system in the brain.Accumulating evidence indicates thatglymphatic function is impaired not only in central nervous system disorders but also in systemic diseases.Systemic diseases can trigger the inflammatory responses in the central nervous system,occasionally leading to sustained inflammation and functional disturbance of the central nervous system.This review summarizes the current knowledge on the association between glymphatic dysfunction and central nervous system inflammation.In addition,we discuss the hypothesis that disease conditions initially associated with peripheral inflammation ove rwhelm the performance of the glymphatic system,thereby triggering central nervous system dysfun ction,chronic neuroinflammation,and neurodegeneration.Future research investigating the role of the glymphatic system in neuroinflammation may offer innovative therapeutic approaches for central nervous system disorders.展开更多
Drugs that lack the ability to cross the blood- brain barrier (BBB) need to be placed directly into the central nervous system. Our laboratory studies the involve- ment of the glutamatergic system in the aggressiven...Drugs that lack the ability to cross the blood- brain barrier (BBB) need to be placed directly into the central nervous system. Our laboratory studies the involve- ment of the glutamatergic system in the aggressiveness of glioma, and some ligands of glutamate receptors cannot permeate the BBB. Here, glioma-implanted rats were treated by a technique that delivers ligands directly into the cerebrospinal fluid by puncture into the cisterna cerebel- lomedullaris. Rats were anesthetized and fixed in a rodent stereotactic device. The head was gently tilted downwards at an angle that allowed exposure of the cisterna. Injection into the cisterna was done freehand using a gingival needle coupled to a microsyringe. The efficiency of intracisternal injection was demonstrated using a methylene blue solu- tion. This type of injection is adaptable for any rodent model using small volumes of a variety of other drugs, and is an interesting method for neuroscience studies.展开更多
Central nervous system(CNS)cancer is a devastating illness with unmet therapeutic needs.Establishing biomarkers that have the potential to guide accurate CNS cancer diagnosis or are helpful in predicting disease progr...Central nervous system(CNS)cancer is a devastating illness with unmet therapeutic needs.Establishing biomarkers that have the potential to guide accurate CNS cancer diagnosis or are helpful in predicting disease progression or therapy response is of great interest.Cerebrospinal fluid(CSF)has been extensively targeted for the detection of molecules that might be useful markers for cancer detection.However,so far very few of such markers have found a standardized routine clinical application.This review examines the current scientific knowledge about the biochemical elements in the CSF that have been reported in the literature as brain cancer biomarkers and highlight reasons why the role of most markers is not yet established in the managment of CNS tumors.展开更多
文摘BACKGROUND The diagnostic value of metagenomic next-generation sequencing(mNGS)in central nervous system(CNS)infectious diseases after empirical treatment has not been reported.AIM To investigate the diagnostic value of mNGS of cerebrospinal fluid(CSF)in the empirically treated CNS infectious diseases.METHODS A total of 262 CSF samples from patients with suspected CNS infections were collected between August 2020 and December 2021.Both mNGS and conventional methods were used for testing.The conventional methods included microbial culture,smear,polymerase chain reaction,etc.RESULTS Among 262 suspected cases,183 cases(69.84%)were diagnosed as CNS infection,including 86 cases of virus infection(47.00%),70 cases of bacterial infection(38.25%)and 27 cases of fungal infection(14.76%).The sensitivity and specificity of mNGS were 65.6%(95%CI:58.2%-72.3%)and 89.6%(95%CI:79.1%-95.3%),respectively.The PPV of mNGS was 94.5%(95%CI:88.6%-97.6%),and the NPV was 48.8%(95%CI:39.7%–57.9%).The pathogen detective sensitivity and accuracy of mNGS were higher than those of conventional methods(Sensitivity:65.6%vs 37.2%;P<0.001;Accuracy:72.0%vs 50%,P<0.001).The results showed that compared with conventional methods,mNGS technology was a more sensitive method for the diagnosis of CNS infection after empirical treatment.CONCLUSION mNGS can be a better method applied in the diagnosis of CNS infection after empirical treatment.
基金supported by the National Natural Science Foundation of China, No. 30700858the Research Fund of Capital Medical Development, No. 2009-3047Wushunde Medical Research Fund of Tsinghua University in 2011
文摘The present study analyzed the anatomical association between intracranial subarachnoid space and the cervical lymphatic system. X-ray contrast medium and Microfil (Microfil compounds fill and opacify microvascular and other spaces of non-surviving animals and post-mortem tissue under physiological injection pressure) were injected into the cisterna magna of the rabbit, and perineural routes of cerebrospinal fluid outflow into the lymphatic system were visualized. Under a surgical operating microscope, Microfil was found within the subarachnoid space and along the olfactory nerves. At the nasal mucosa, a lymphatic network was identified near the olfactory nerves, which crossed the nasopharyngeal region and finally emptied into the superficial and deep cervical lymph nodes. Under a light microscope, Microfil was visible around the olfactory nerves and within lymphatic vessels. These results suggested that cerebrospinal fluid drained from the subarachnoid space along the olfactory nerves to nasal lymphatic vessels, which in turn, emptied into the cervical lymph nodes. This anatomical route, therefore, allowed connection between the central nervous system and the lymphatic system.
文摘As the key producer of cerebrospinal fluid(CSF),the choroid plexus(CP) provides a unique protective system in the central nervous system.CSF components are not invariable and they can change based on the pathological conditions of the central nervous system.The purpose of the present study was to assess the effects of non-traumatic and traumatic CSF on the differentiation of multipotent stem-like cells of CP into the neural and/or glial cells.CP epithelial cells were isolated from adult male rats and treated with human non-traumatic and traumatic CSF.Alterations in m RNA expression of Nestin and microtubule-associated protein(MAP2),as the specific markers of neurogenesis,and astrocyte marker glial fibrillary acidic protein(GFAP) in cultured CP epithelial cells were evaluated using quantitative real-time PCR.The data revealed that treatment with CSF(non-traumatic and traumatic) led to increase in m RNA expression levels of MAP2 and GFAP.Moreover,the expression of Nestin decreased in CP epithelial cells treated with non-traumatic CSF,while treatment with traumatic CSF significantly increased its m RNA level compared to the cells cultured only in DMEM/F12 as control.It seems that CP epithelial cells contain multipotent stem-like cells which are inducible under pathological conditions including exposure to traumatic CSF because of its compositions.
文摘Superficial siderosis of the central nervous system (SSCNS) is usually caused by chronic subarachnoid hemorrhage which leads to the accumulation of hemosiderin in the subpial layers of the brain and the spinal cord. The exact clinical manifestations and T2-weighted magnetic resonance imaging (MRI) the patient presented here is diagnosed SSCNS mainly due to the cytology of cerebrospinal fluid (CCSF) and the superficial siderosis of T2-weighted MRI. CCSF can be a good complementary to the diagnosis of SSCNS.
基金supported by the National Natural Science Foundation of China,Nos.82071249 and 81771207 (both to CH)。
文摘The glymphatic system is a relatively recently identified fluid exchange and transpo rt system in the brain.Accumulating evidence indicates thatglymphatic function is impaired not only in central nervous system disorders but also in systemic diseases.Systemic diseases can trigger the inflammatory responses in the central nervous system,occasionally leading to sustained inflammation and functional disturbance of the central nervous system.This review summarizes the current knowledge on the association between glymphatic dysfunction and central nervous system inflammation.In addition,we discuss the hypothesis that disease conditions initially associated with peripheral inflammation ove rwhelm the performance of the glymphatic system,thereby triggering central nervous system dysfun ction,chronic neuroinflammation,and neurodegeneration.Future research investigating the role of the glymphatic system in neuroinflammation may offer innovative therapeutic approaches for central nervous system disorders.
基金supported by Coordenacao de Aperfeicoamento de Pessoal de Nível Superior(CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)-Edital Doencas Neurodegenerativas+1 种基金Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul(FAPERGS)Financiadora de Estados e Projetos(FINEP)
文摘Drugs that lack the ability to cross the blood- brain barrier (BBB) need to be placed directly into the central nervous system. Our laboratory studies the involve- ment of the glutamatergic system in the aggressiveness of glioma, and some ligands of glutamate receptors cannot permeate the BBB. Here, glioma-implanted rats were treated by a technique that delivers ligands directly into the cerebrospinal fluid by puncture into the cisterna cerebel- lomedullaris. Rats were anesthetized and fixed in a rodent stereotactic device. The head was gently tilted downwards at an angle that allowed exposure of the cisterna. Injection into the cisterna was done freehand using a gingival needle coupled to a microsyringe. The efficiency of intracisternal injection was demonstrated using a methylene blue solu- tion. This type of injection is adaptable for any rodent model using small volumes of a variety of other drugs, and is an interesting method for neuroscience studies.
文摘Central nervous system(CNS)cancer is a devastating illness with unmet therapeutic needs.Establishing biomarkers that have the potential to guide accurate CNS cancer diagnosis or are helpful in predicting disease progression or therapy response is of great interest.Cerebrospinal fluid(CSF)has been extensively targeted for the detection of molecules that might be useful markers for cancer detection.However,so far very few of such markers have found a standardized routine clinical application.This review examines the current scientific knowledge about the biochemical elements in the CSF that have been reported in the literature as brain cancer biomarkers and highlight reasons why the role of most markers is not yet established in the managment of CNS tumors.