BACKGROUND: Under normal conditions, excitatory amino acids are dynamically balanced with inhibitory amino acids. Excitatory amino acids have been implicated in perinatal brain injury. OBJECTIVE: To investigate diff...BACKGROUND: Under normal conditions, excitatory amino acids are dynamically balanced with inhibitory amino acids. Excitatory amino acids have been implicated in perinatal brain injury. OBJECTIVE: To investigate differences in the levels of the excitatory amino acids glutamic acid and aspartic acid, and the inhibitory amino acid gamma-aminobutyric acid (GABA) in the cerebrospinal fluid (CSF) of children with spastic cerebral palsy or athetotic cerebral palsy. DESIGN, TIME AND SETTING: Case-control exploratory observation of neurotransmitter in patients. The experiment was performed in the Pediatrics Department of the Second Affiliated Hospital of Changsha Medical College, the Cerebral Palsy Center of Xiangtan Affiliated Hospital of South China University and the Pediatrics Department of Xiangya Hospital, between February 2006 and May 2007. PARTICIPANTS: We selected 27 children with cerebral palsy, including 13 with spastic cerebral palsy and 14 with athetotic cerebral palsy. We selected 10 patients who were not affected by any neurological disease as controls. METHODS: Two mL blood-free CSF was harvested between the third and fourth lumbar vertebrae of each patient after anesthesia, and stored at -70℃. One mL CSF was mixed with 10 mg sulfosalicylic acid and placed in ice-bath for 10 minutes, then centrifuged 2 000 g for 10 minutes. The supernatant was collected for amino acid quantitation. MAIN OUTCOME MEASURES: The concentrations of glutamic acid, aspartic acid and GABA in the CSF were determined by high-performance liquid chromatography and fluorometric method. The correlation of glutamic acid, aspartic acid and GABA levels with muscular tension in children with cerebral palsy was analyzed using linear dependence. RESULTS: The concentration of GABA was significantly lower in both spastic cerebral palsy and athetotic cerebral palsy patients than in the control group (P 〈 0.01). Glutamic acid and aspartic acid were significantly higher in both cerebral palsy groups than in the control group (P 〈 0.05-0.01). The concentration of GABA was significantly decreased in spastic cerebral palsy patients compared with the athetotic cerebral palsy group (P 〈 0.05). Muscular tension was positively correlated with the concentration of glutamic acid in spastic cerebral palsy patients (P 〈 0.05) but there was no significant correlation between aspartic acid or GABA and muscular tension (P 〉 0.05). CONCLUSION: Spastic cerebral palsy and athetotic cerebral palsy patients exhibit an imbalance of excitatory amino acids and inhibitory amino acids in their CSF: an increase in glutamic acid and aspartic acid, and a decrease in GABA. Amino acid levels are different in the CSF in varied types of cerebral palsy.展开更多
Objective To study the changes of biomarkers in cerebrospinal fluid(CSF) in cerebral amyloid angiopathy(CAA) dementia and Alzheimer's disease.Methods Levels of amyloid protein β(Aβ42,Aβ40) and phosphorylated Ta...Objective To study the changes of biomarkers in cerebrospinal fluid(CSF) in cerebral amyloid angiopathy(CAA) dementia and Alzheimer's disease.Methods Levels of amyloid protein β(Aβ42,Aβ40) and phosphorylated Tau-protein(P-tau) in CSF and ratio of Aβ42/Aβ40 were tested in 5 cases with CAA dementia and 20 cases with Alzheimer's disease collected at Peking Union Medical College Hospital from December 2001 to March 2011.Results The levels of Aβ42,Aβ40,and P-tau in CSF and ratio of Aβ42/Aβ40 were(660.4±265.2) ng/L,(7111.0±1033.4) ng/L,(71.8±51.5) ng/L,and 0.077±0.033,respectively in CAA dementia and(663.6±365.6) ng/L,(5115.0±2931.1) ng/L,(47.7±38.8) ng/L,and 0.192±0.140,respectively in Alzheimer's disease patients.There were no statistically significant differences between CAA dementia and Alzheimer's disease in terms of these CSF biomarkers(all P>0.05).Conclusion Measurements of CSF biomarkers may not be helpful in differential diagnosis of CAA and Alzheimer's disease.展开更多
In this paper,we present a mathematical model of the cerebrospinal fluid(CSF)formation based on fluid mechanics concepts.Maintenance of intracranial pressure(IP)in the cases of patients with head injury has been a pro...In this paper,we present a mathematical model of the cerebrospinal fluid(CSF)formation based on fluid mechanics concepts.Maintenance of intracranial pressure(IP)in the cases of patients with head injury has been a problem for some time now.Cerebrospinal fluid is one of the cranial vault content that influences the normality of the IP.It was assumed that cerebrospinal fluid(CSF)formation begins as plasma,展开更多
The difference of composition in extracellular fluid in brain parenchyma and CSF suggests that CSF-brain barrier(CBB)is objective,which is necessary to maintain the stability of their internal environment.However,the ...The difference of composition in extracellular fluid in brain parenchyma and CSF suggests that CSF-brain barrier(CBB)is objective,which is necessary to maintain the stability of their internal environment.However,the information exchange between brain and CSF is also objective.For example,CSF is changes during diseases,the application of drugs(such as lumbar anesthesia)or tissue transplantation via the CSF pathway may also produce central(cerebral)effects.Who breaks through the barrier and mediates brain-CSF communication?Since 1992,we have found that the peripheral nerve tracer CB-HRP injected into the lateral ventricle of mice,rats and macaques is blocked in the ventricle wall and can only run in CSF,but a large number of CB-HRP-positive labeled neurons can be seen in specific parts of the brain stem parenchyma.Understandably,these neurons touch markers in CSF.Otherwise,they cannot be tagged.展开更多
Evodiamine,rutaecarpine,and dehydroevodiamine have been demonstrated as the major alkaloids in the fruits of Euodia rutaecarpa,a well-known traditional Chinese medicine with central nervous system activities.To study ...Evodiamine,rutaecarpine,and dehydroevodiamine have been demonstrated as the major alkaloids in the fruits of Euodia rutaecarpa,a well-known traditional Chinese medicine with central nervous system activities.To study their cerebrospinal fluid pharmacokinetics and cerebral nuclei distribution,the alkaloids were mixed at the weight ratio of 1:1:1 and orally administered via gavage to the rats at each dose of 15 mg/kg.A quick and reliable ultra-performance liquid chromatographic-tandem mass spectrometry method was developed and applied for the simultaneous analysis of the alkaloids in rat cerebrospinal fluid and cerebral nuclei collected at different time points.Non-compartmental pharmacokinetic profiles were calculated,and the distribution in cerebral nuclei was compared.All the tested compounds were absorbed into rat cerebrospinal fluid and distributed to the brain nuclei quickly.Their distribution in different nuclei varied,as evodiamine mainly in cerebellum and brainstem,rutaecarpine with its maximum in the brainstem,and dehydroevodiamine mostly in the cerebellum and hippocampus.They were eliminated from the brain rapidly without long-time accumulation.In summary,this study revealed the targeting discrepancy of evodiamine,rutaecarpine,and dehydroevodiamine in the brain,and highlighted the possibility for drug candidates in the encephalopathy treatment of the fruits of E.rutaecarpa.展开更多
Objective: To probe into the significance of Nitric Oxide (NO) in ischemic cerebral damage and effect of ligustrazine on it. Methods: The NO contents in cerebrospinal fluid (CSF) and plasma of 20 controls and 62 patie...Objective: To probe into the significance of Nitric Oxide (NO) in ischemic cerebral damage and effect of ligustrazine on it. Methods: The NO contents in cerebrospinal fluid (CSF) and plasma of 20 controls and 62 patients with arteriosclerotic thrombotic cerebral infarction (ligustrazine group and common treatment group) were determined with Griess method before and after treatment. Results:The NO content in CSF before treatment was higher in severe type, it was higher than that in moderate type, and than that in mild type,again higher than that in control group (all P < 0. 05) and was positively correlated with the size of infarction (P < 0. 01 ). There was no significant difference between the plasma NO content of patients and that of control group (P < 0. 05), but there was a trend that plasma NO content decreased as the patient's condition worsened. After treatment, the curative effect and plasma NO content of ligustrazine group were both markedly higher than those of common treatment group (P < 0. 05, 0. 05 ).There were no significant differences between CSF NO contents of the two groups, respectively, and that of control group (P > 0. 05,0. 05). Conclusion: Excessive NO produced in brain tissue and insufficient plasma NO participate the course of ischemic brain damage.Ligustrazine could increase the contents of plasma NO selectively.Original article on CJIM(Chin) 1998; 18(6). 342展开更多
Background:Alterations in the expression of human kallikrein-related peptidases(KLKs)have been described in patients with Alzheimer’s disease(AD).We elucidated the suitability of KLK6,KLK8 and KLK10 to distinguish AD...Background:Alterations in the expression of human kallikrein-related peptidases(KLKs)have been described in patients with Alzheimer’s disease(AD).We elucidated the suitability of KLK6,KLK8 and KLK10 to distinguish AD from NC and explored associations with established AD biomarkers.Methods:KLK levels in cerebrospinal fluid(CSF),as determined by ELISA,were compared between 32 AD patients stratified to A/T/(N)system with evidence for amyloid pathology and of 23 normal controls with normal AD biomarkers.Associations between KLK levels and clinical severity,CSF and positron emission tomography(PET)based AD biomarkers were tested for.Results:Levels of KLK6 and KLK10 were significantly increased in AD.KLK6 differed significantly between AD A+/T+/N+and AD A+/T−/N+or NC with an AUC of 0.922.CSF pTau and tTau levels were significantly associated with KLK6 in AD.Conclusions:KLK6 deserves further investigations as a potential biomarker of Tau pathology in AD.展开更多
Progressive supranuclear palsy,corticobasal degeneration,multiple system atrophy and dementia with Lewy bodies are the most common causes of atypical Parkinsonism and enter the differential diagnosis of Parkinson'...Progressive supranuclear palsy,corticobasal degeneration,multiple system atrophy and dementia with Lewy bodies are the most common causes of atypical Parkinsonism and enter the differential diagnosis of Parkinson's disease.multiple system atrophy,dementia with Lewy bodies and Parkinson's disease are synucleinopathies,whereas progressive supranuclear palsy and corticobasal degeneration are tauopathies.Multiple cerebrospinal fluid markers have been applied on cohorts of patients with Parkinsonism,with the aim to develop biomarkers for these disorders.Total tau(τΤ),phosphorylated tau at threonine 181(τP-181)and amyloid-beta with 42 amino acids(Aβ42)are considered classical biomarkers for Alzheimer's disease.The aim of the present study is to review the literature regarding these classical cerebrospinal fluid biomarkers in cohorts with Parkinsonism,as well as present data on novel approaches regarding analysis of these proteins.展开更多
Objectives: SELDI-TOF and MALDI-TOF mass spectrometry (MS) are laser desorption technologies that allow for proteomic examination of molecular masses in small amounts of samples. In a precedent study, the feasibility ...Objectives: SELDI-TOF and MALDI-TOF mass spectrometry (MS) are laser desorption technologies that allow for proteomic examination of molecular masses in small amounts of samples. In a precedent study, the feasibility of SELDI-TOF MS assessment of proteins in cerebrospinal fluid and tumor cyst fluid had been shown. In the present study, we analyzed whether MALDI-TOF MS examination of these fluids leads to comparable results. Methods: During neurosurgical intervention, cyst fluids from 24 glioblastomas and 15 metastases were collected. As control, cerebrospinal fluid samples from 23 patients were obtained. The samples were prepared using a protocol optimized for MALDI-TOF MS. Mass spectra were recorded and peaks were extracted, characterized by masses and relative intensities. These peaks were analyzed for statistically significant differences between the diagnosis groups and compared to SELDI-TOF MS data. Results: 41 protein peaks known from the SELDI-TOF MS analysis could be confirmed by MALDI-TOF MS, and the cellular expression of the proteins LuzP6 and ApoC1, corresponding to the protein peaks 6433 and 6632, was shown immunohistochemically in glioblas-toma tissue. The MALDI-TOF spectrometry extends the range of analysis down to 1.4 kDa, whereas the upper detection limit lies below 23 kDa. Discussion: The presented proteomic approach yields an inventory of protein masses, found in the tumor cyst at the time of puncture. It does not reveal pathophysiologic, metabolic or secretory pathways that lead to the presence of proteins in the cyst. These have to be assessed immunohistochemically or on mRNA level in the surrounding tumor cells. Conclusion: MALDI-TOF MS of tumor cyst fluid discloses protein sizes, overexpressed or lost in tumor tissue. A thorough proteomic work-up is needed to identify the underlying proteins and metabolic pathways.展开更多
基金a grant from Health Department of Hunan Province,No.B2006-204
文摘BACKGROUND: Under normal conditions, excitatory amino acids are dynamically balanced with inhibitory amino acids. Excitatory amino acids have been implicated in perinatal brain injury. OBJECTIVE: To investigate differences in the levels of the excitatory amino acids glutamic acid and aspartic acid, and the inhibitory amino acid gamma-aminobutyric acid (GABA) in the cerebrospinal fluid (CSF) of children with spastic cerebral palsy or athetotic cerebral palsy. DESIGN, TIME AND SETTING: Case-control exploratory observation of neurotransmitter in patients. The experiment was performed in the Pediatrics Department of the Second Affiliated Hospital of Changsha Medical College, the Cerebral Palsy Center of Xiangtan Affiliated Hospital of South China University and the Pediatrics Department of Xiangya Hospital, between February 2006 and May 2007. PARTICIPANTS: We selected 27 children with cerebral palsy, including 13 with spastic cerebral palsy and 14 with athetotic cerebral palsy. We selected 10 patients who were not affected by any neurological disease as controls. METHODS: Two mL blood-free CSF was harvested between the third and fourth lumbar vertebrae of each patient after anesthesia, and stored at -70℃. One mL CSF was mixed with 10 mg sulfosalicylic acid and placed in ice-bath for 10 minutes, then centrifuged 2 000 g for 10 minutes. The supernatant was collected for amino acid quantitation. MAIN OUTCOME MEASURES: The concentrations of glutamic acid, aspartic acid and GABA in the CSF were determined by high-performance liquid chromatography and fluorometric method. The correlation of glutamic acid, aspartic acid and GABA levels with muscular tension in children with cerebral palsy was analyzed using linear dependence. RESULTS: The concentration of GABA was significantly lower in both spastic cerebral palsy and athetotic cerebral palsy patients than in the control group (P 〈 0.01). Glutamic acid and aspartic acid were significantly higher in both cerebral palsy groups than in the control group (P 〈 0.05-0.01). The concentration of GABA was significantly decreased in spastic cerebral palsy patients compared with the athetotic cerebral palsy group (P 〈 0.05). Muscular tension was positively correlated with the concentration of glutamic acid in spastic cerebral palsy patients (P 〈 0.05) but there was no significant correlation between aspartic acid or GABA and muscular tension (P 〉 0.05). CONCLUSION: Spastic cerebral palsy and athetotic cerebral palsy patients exhibit an imbalance of excitatory amino acids and inhibitory amino acids in their CSF: an increase in glutamic acid and aspartic acid, and a decrease in GABA. Amino acid levels are different in the CSF in varied types of cerebral palsy.
文摘Objective To study the changes of biomarkers in cerebrospinal fluid(CSF) in cerebral amyloid angiopathy(CAA) dementia and Alzheimer's disease.Methods Levels of amyloid protein β(Aβ42,Aβ40) and phosphorylated Tau-protein(P-tau) in CSF and ratio of Aβ42/Aβ40 were tested in 5 cases with CAA dementia and 20 cases with Alzheimer's disease collected at Peking Union Medical College Hospital from December 2001 to March 2011.Results The levels of Aβ42,Aβ40,and P-tau in CSF and ratio of Aβ42/Aβ40 were(660.4±265.2) ng/L,(7111.0±1033.4) ng/L,(71.8±51.5) ng/L,and 0.077±0.033,respectively in CAA dementia and(663.6±365.6) ng/L,(5115.0±2931.1) ng/L,(47.7±38.8) ng/L,and 0.192±0.140,respectively in Alzheimer's disease patients.There were no statistically significant differences between CAA dementia and Alzheimer's disease in terms of these CSF biomarkers(all P>0.05).Conclusion Measurements of CSF biomarkers may not be helpful in differential diagnosis of CAA and Alzheimer's disease.
文摘In this paper,we present a mathematical model of the cerebrospinal fluid(CSF)formation based on fluid mechanics concepts.Maintenance of intracranial pressure(IP)in the cases of patients with head injury has been a problem for some time now.Cerebrospinal fluid is one of the cranial vault content that influences the normality of the IP.It was assumed that cerebrospinal fluid(CSF)formation begins as plasma,
文摘The difference of composition in extracellular fluid in brain parenchyma and CSF suggests that CSF-brain barrier(CBB)is objective,which is necessary to maintain the stability of their internal environment.However,the information exchange between brain and CSF is also objective.For example,CSF is changes during diseases,the application of drugs(such as lumbar anesthesia)or tissue transplantation via the CSF pathway may also produce central(cerebral)effects.Who breaks through the barrier and mediates brain-CSF communication?Since 1992,we have found that the peripheral nerve tracer CB-HRP injected into the lateral ventricle of mice,rats and macaques is blocked in the ventricle wall and can only run in CSF,but a large number of CB-HRP-positive labeled neurons can be seen in specific parts of the brain stem parenchyma.Understandably,these neurons touch markers in CSF.Otherwise,they cannot be tagged.
基金National Natural Science Foundation of China(Grant No.81773865)the National Key R&D Program of China(Grant No.2018YFC1704500,2018YFC1704506)。
文摘Evodiamine,rutaecarpine,and dehydroevodiamine have been demonstrated as the major alkaloids in the fruits of Euodia rutaecarpa,a well-known traditional Chinese medicine with central nervous system activities.To study their cerebrospinal fluid pharmacokinetics and cerebral nuclei distribution,the alkaloids were mixed at the weight ratio of 1:1:1 and orally administered via gavage to the rats at each dose of 15 mg/kg.A quick and reliable ultra-performance liquid chromatographic-tandem mass spectrometry method was developed and applied for the simultaneous analysis of the alkaloids in rat cerebrospinal fluid and cerebral nuclei collected at different time points.Non-compartmental pharmacokinetic profiles were calculated,and the distribution in cerebral nuclei was compared.All the tested compounds were absorbed into rat cerebrospinal fluid and distributed to the brain nuclei quickly.Their distribution in different nuclei varied,as evodiamine mainly in cerebellum and brainstem,rutaecarpine with its maximum in the brainstem,and dehydroevodiamine mostly in the cerebellum and hippocampus.They were eliminated from the brain rapidly without long-time accumulation.In summary,this study revealed the targeting discrepancy of evodiamine,rutaecarpine,and dehydroevodiamine in the brain,and highlighted the possibility for drug candidates in the encephalopathy treatment of the fruits of E.rutaecarpa.
文摘Objective: To probe into the significance of Nitric Oxide (NO) in ischemic cerebral damage and effect of ligustrazine on it. Methods: The NO contents in cerebrospinal fluid (CSF) and plasma of 20 controls and 62 patients with arteriosclerotic thrombotic cerebral infarction (ligustrazine group and common treatment group) were determined with Griess method before and after treatment. Results:The NO content in CSF before treatment was higher in severe type, it was higher than that in moderate type, and than that in mild type,again higher than that in control group (all P < 0. 05) and was positively correlated with the size of infarction (P < 0. 01 ). There was no significant difference between the plasma NO content of patients and that of control group (P < 0. 05), but there was a trend that plasma NO content decreased as the patient's condition worsened. After treatment, the curative effect and plasma NO content of ligustrazine group were both markedly higher than those of common treatment group (P < 0. 05, 0. 05 ).There were no significant differences between CSF NO contents of the two groups, respectively, and that of control group (P > 0. 05,0. 05). Conclusion: Excessive NO produced in brain tissue and insufficient plasma NO participate the course of ischemic brain damage.Ligustrazine could increase the contents of plasma NO selectively.Original article on CJIM(Chin) 1998; 18(6). 342
基金This work was supported by the German Research Foundation(DFG)and the Technical University of Munich(TUM)in the framework of the Open Access Publishing Program.
文摘Background:Alterations in the expression of human kallikrein-related peptidases(KLKs)have been described in patients with Alzheimer’s disease(AD).We elucidated the suitability of KLK6,KLK8 and KLK10 to distinguish AD from NC and explored associations with established AD biomarkers.Methods:KLK levels in cerebrospinal fluid(CSF),as determined by ELISA,were compared between 32 AD patients stratified to A/T/(N)system with evidence for amyloid pathology and of 23 normal controls with normal AD biomarkers.Associations between KLK levels and clinical severity,CSF and positron emission tomography(PET)based AD biomarkers were tested for.Results:Levels of KLK6 and KLK10 were significantly increased in AD.KLK6 differed significantly between AD A+/T+/N+and AD A+/T−/N+or NC with an AUC of 0.922.CSF pTau and tTau levels were significantly associated with KLK6 in AD.Conclusions:KLK6 deserves further investigations as a potential biomarker of Tau pathology in AD.
文摘Progressive supranuclear palsy,corticobasal degeneration,multiple system atrophy and dementia with Lewy bodies are the most common causes of atypical Parkinsonism and enter the differential diagnosis of Parkinson's disease.multiple system atrophy,dementia with Lewy bodies and Parkinson's disease are synucleinopathies,whereas progressive supranuclear palsy and corticobasal degeneration are tauopathies.Multiple cerebrospinal fluid markers have been applied on cohorts of patients with Parkinsonism,with the aim to develop biomarkers for these disorders.Total tau(τΤ),phosphorylated tau at threonine 181(τP-181)and amyloid-beta with 42 amino acids(Aβ42)are considered classical biomarkers for Alzheimer's disease.The aim of the present study is to review the literature regarding these classical cerebrospinal fluid biomarkers in cohorts with Parkinsonism,as well as present data on novel approaches regarding analysis of these proteins.
文摘Objectives: SELDI-TOF and MALDI-TOF mass spectrometry (MS) are laser desorption technologies that allow for proteomic examination of molecular masses in small amounts of samples. In a precedent study, the feasibility of SELDI-TOF MS assessment of proteins in cerebrospinal fluid and tumor cyst fluid had been shown. In the present study, we analyzed whether MALDI-TOF MS examination of these fluids leads to comparable results. Methods: During neurosurgical intervention, cyst fluids from 24 glioblastomas and 15 metastases were collected. As control, cerebrospinal fluid samples from 23 patients were obtained. The samples were prepared using a protocol optimized for MALDI-TOF MS. Mass spectra were recorded and peaks were extracted, characterized by masses and relative intensities. These peaks were analyzed for statistically significant differences between the diagnosis groups and compared to SELDI-TOF MS data. Results: 41 protein peaks known from the SELDI-TOF MS analysis could be confirmed by MALDI-TOF MS, and the cellular expression of the proteins LuzP6 and ApoC1, corresponding to the protein peaks 6433 and 6632, was shown immunohistochemically in glioblas-toma tissue. The MALDI-TOF spectrometry extends the range of analysis down to 1.4 kDa, whereas the upper detection limit lies below 23 kDa. Discussion: The presented proteomic approach yields an inventory of protein masses, found in the tumor cyst at the time of puncture. It does not reveal pathophysiologic, metabolic or secretory pathways that lead to the presence of proteins in the cyst. These have to be assessed immunohistochemically or on mRNA level in the surrounding tumor cells. Conclusion: MALDI-TOF MS of tumor cyst fluid discloses protein sizes, overexpressed or lost in tumor tissue. A thorough proteomic work-up is needed to identify the underlying proteins and metabolic pathways.