ABSTRACT
Glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), neurofilament light chain (NFL), tau and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) are five neuroglial proteins that are used as CSF or blood biomarkers of tissue damage in the nervous system. There is incomplete knowledge of how the concentration of these proteins differs between anatomical regions in the CNS as previous studies have focused on gene expression or non-quantitative protein analyses, limiting the interpretability of these biomarkers. The purpose of this study was to create a map of the tissue content of these proteins in different regions of the CNS. The concentrations of the investigated proteins were determined with ELISA in post mortem tissue homogenates from 17 selected anatomical regions in the CNS from ten deceased donors aged 24 to 50 years. When appropriate, the protein concentrations were adjusted for post-mortem interval. In total, 168 tissue samples were analysed. There was a substantial variation in the concentrations of GFAP, MBP, NFL, tau and UCHL1 between different CNS regions. Highly myelinated areas of the CNS had tenfold higher MBP concentration than cerebral cortex, whereas tau showed an inverse pattern. GFAP, NFL and tau displayed an anteroposterior gradient in cerebral white matter. The cerebellum had low concentrations of all the investigated proteins. In conclusion, the tissue concentrations of GFAP, MBP, NFL, tau and UCHL1 were determined throughout the CNS. This information can be used as a reference when interpreting circulating levels of these biomarkers in relation to the extent and localisation of CNS-damaging processes.
Subject(s)
Brain , White Matter , Autopsy , Biomarkers , Humans , Ubiquitin ThiolesteraseABSTRACT
Objective To study the effects of ibuprofen on the growth and development of oligodendrocytes. Methods A total of 6 clean and healthy adult female SD (Sprague Dawley) rats were used for extracting and culturing of oligodendrocytes(OLs).Lysophosphatidic acid(LPA)was then added,and the morphological changes of OLs pre-treatment and post-treatment were observed. Then 6 newborn rats (born 24-48 h) were used for mixed glial cell extraction from the cortex, then the OPCs were inoculated into the culture plates and randomly divided into control group, ibuprofen group, lysophosphatidic acid(LPA)group and LPA+ibuprofen group.After the adhering of the cells in each group for three days, cell morphology was observed,and the drugs were added as interventions.The control group was treated with normal saline, and the other 3 groups were added with saline solution of ibuprofen(100 μmol/L),LPA(1.0 μmol/L)and the mixture of them. The cell morphological changes were observed after 7-day intervention.The morphology of OPCs and OLs were observed by immunofluorescence staining through OPCs'specific immune markers (platelet-derived growth factor receptor alpha, PDGFR-α)and OLs'specific immune markers(myelin basic protein,MBP)along with cell count of mature OLs.Western blot assay was used to detect the relative expression level of MBP in each group. Results After the treatment with LPA to the mature OLs,protrusions were shrinking and became very sparse.The morphology of cells developed well in each group after cell adhering for 3 days. After drug intervention for 7 days, more cell protrusions and branches were observed in ibuprofen group and LPA+ibuprofen group than those of the control group and LPA group.The results of cell count showed that the number of MBP positive cells was significantly higher in the ibuprofen group and LPA+ibuprofen group than that in the control group and LPA group(P<0.01).The results of Western blot assay showed that the MBP protein expression was significantly less in LPA group than the other three groups (P<0.01), and the expression was significantly higher in the ibuprofen group than that of LPA+ibuprofen group (P<0.01). Conclusion LPA has a toxic effect on the growth and development of OPCs, and it has an inhibitory effect on the normal growth of mature OLs. A certain concentration of ibuprofen can significantly inhibit the cytotoxicity of LPA on OPCs and OLs,and promote the formation and maintenance of mature OLs.
ABSTRACT
Objective To investigate the therapeutic effect of interleukin-2(IL-2)on experimental autoimmune encephalomyelitis(EAE)mice.Methods After establishment of the EAE(experimental autoimmune encephalomyelitis) mouse models with MOG35-55 polypeptides,the mice were grouped according to the neurological function score and divided into control group,EAE group and low dose IL-2 treatment group.A double blind method was used to evaluate the neuro-logical impairment in mice.On the 29th day,pathological experiments were carried out in the mice's brain and spinal cord, hematoxylin-eosin staining was used to evaluate the scoring of inflammatory cell infiltration and luxol fast blue staining was used to evaluate the scoring of demyelinating.The proportion of regulatory T cells(Treg)and NK cells(natural killer cell, NK)was detected by flow cytometry,and the immunohistochemical method was used to detect the expressions of glial fibril -lary acidic protein(GFAP)and myelin basic protein(MBP)in the spinal cord.Results Compared with the EAE group, the neurological function score, the inflammatory cell infiltration score and the demyelinating score of the low dose IL-2 treatment group were reduced.The proportion of Treg cells in the low dose IL-2 treatment group was significantly higher than that in the EAE group,and the proportion of NK cells in the low dose IL-2 treatment group was slightly higher than that in the EAE group The expression of GFAP and MBP was detected by immunohistochemistry.The expression level of GFAP in low dose IL-2 treatment group was significantly lower than that in the EAE group,while the expression level of MBP was higher than that in the EAE group.Conclusion Low dose IL-2 has significant therapeutic effect on EAE mice.
ABSTRACT
Objective To determine the effect of induction of immune tolerance by intrathymic injection of myelin basic protein (MBP) for treatment of surgical brain injury (SBI) in rats.Methods Twenty-four male SD rats were divided into experimental group,control group and sham group with 8 rats each,according to the random number table.SBI model was established in experimental group and control group.Thymuses were exposed and injected with MBP (experimental group) or saline (control group) respectively.Sham group received craniotomy without durotomy and thymus paracentesis.Modified neurological severity score (MNSS),cerebral edema volume,levels of peripheral blood proinflammatory cytokine interleukin (IL)-2 and anti-inflammatory cytokine IL-4,and CD4 +/CD8 + T-cell ratio were measured at postoperative 1,3,7,14 and 21 d.Results MNSS between control and experimental groups differed significantly at each time point (P < 0.05).Compared to sham group,MNSS in experimental group was recovered the same value at 21 d (P > 0.05),but in control group remained high over the study (P < 0.05).Less cerebral edema was observed in control and experimental groups than in control group at each time point (P < 0.05),but all were lower than these in sham group (P < 0.05).Lower IL-2 concentrations and higher IL-4 concentrations were observed in experimental group than in control group at 3,7 and 14 d (P <0.05).Compared to sham group,IL-2 concentrations in experimental group and IL-4 concentrations in control group revealed no significant differences at each time point (P >0.05).CD4 +/CD8 + T-cell ratio between experimental group and control group revealed significant difference at 1,7 and 14 d (P <0.05).CD4 +/CD8 + T-cell ratio in experimental group and control group recovered to the same level in sham group at 7 and 21 d(P > 0.05).Conclusion Induction of immune tolerance through intrathymic injection of MBP can reduce neurological deficit and brain edema and facilitate the recovery of function from SBI.
ABSTRACT
Pancreatic encephalopathy (PE)is one of the severe complications of severe acute pancreatitis (SAP).Early diagnosis mostly depends on the history of disease as well as clinical symptoms and signs.PE progresses rapidly and is often complicated by multiple organ dysfunction,and it may finally develop into multiple organ failure with a high fatality rate if not treated in time.It is currently known that de-myelination is one of the important pathological features of this disease,with fat -soluble demyelination of cerebral gray matter and white matter,as well as inflammatory changes such as hemorrhage and edema.The target antigen of demyelinating lesions,however,is myelin basic protein (MBP).This paper reviews the changes in MBP levels in the demyelinating lesions of the central nervous system among PE pa-tients,with the purpose of providing clues for the early diagnosis and prognostic study of demyelinating lesions in PE.
ABSTRACT
Objective To investigate the effect and significance of minimally invasive removal of intracranial hematoma on the blood-brain barrier in patients with intracerebral hemorrhage (ICH).Methods Clinical data of 20 patients with ICH were randomly selected and received minimally invasive surgery (operative group) and 20 patients with ICH received expectant treatment therapy (expectant treatment group) were analyzed retrospectively,and 20 healthy people were randomly collected for control group.The blood-brain barrier (BBB) and serum myelin basic protein (MBP) concentration were analyzed.Results The BBB index of the iperative group was 0.0075 ± 0.0007,the expectant treatment group was 0.0083 ± 0.0006 and the control group was 0.0068 ± 0.0004.The BBB index in the operative group was significantly lower than that in the expectant treatment group (P < 0.05),and the BBB index in these two groups was significantly higher than that in the control group (P< 0.01).The serum MBP concentration in the operative group was (3.29 ± 1.55) μg/L,the expectant treatment group was (6.55 ± 3.78) μg/L,and the control group was (1.12 ± 0.48) μ g/L.The serum MBP concentration in the operative group was significantly lower than that in the expectant treatment group (P < 0.05),and these two groups were significantly higher than the control group (P < 0.01).Conclusions The permeability of BBB in patients with ICH are increased,the BBB index and the serum MBP concentration in patients with ICH are increased,minimally invasive surgery can reduce the lesion of cytotoxicity to BBB and cerebral edema.
ABSTRACT
ObjectiveTo observe the influence of mini-invasive evacuation of hematoma for myelin basic protein (MBP) and neuron-specific enolase (NSE) in patients with cerebral hemorrhage.Methods Eighty patients with cerebral hemorrhage were divided into group A and group B by random digits table method with 40 cases each.The patients in group A were given conservation treatment.The patients in group B were given mini-invasive evacuation of hematoma treatment.At the same time 30 cases of healthy people randomly were selected as control group.The serum MBP and NSE were determined before treatment,after treatment 1,3,7,14 d in group A and group B.ResultsThe effective rate in group B was 92.5% (37/40),which was higher than that in group A [80.0%(32/40)],there was significant difference (P < 0.05 ).The serum NSE before treatment in group A and group B was higher than that in control group [ (12.8 ± 2.9),( 13.1 ± 2.8 ) μg/L vs.( 5.3 ± 2.4) μg/L],there was significant difference(P < 0.05 ).The serum NSE after treatment in group B was obviously decreased compared with group A.The serum MBP after treatment 1 d was increased,7 d was decreased,that in group B was obviously decreased compared with group A [ (5.4 ± 1.5) μ g/L vs. (6.9 ± 1.3) μ g/L,P < 0.05 ].ConclusionThe method of mini-invasive evacuation of hematoma in treatment of cerebral hemorrhage patients has good effect,and can decrease the serum MBP and NSE.
ABSTRACT
Objective To investigate the accuracy of myeline base protein (MBP) in evaluation of brain injury in patients undergoing cardiac surgery performed under CPB. Methods Thirty-two ASA Ⅱ- Ⅳ patients of both sexes (20 males, 12 females) aged 59-76 yr weighing 52-72 kg undergoing coronary artery bypass grafting (CABG) under CPB were studied. Patients with history of neurological disease were excluded. Preoperative National Institute of Health stroke scale (NIHSS) score ≤ 9. According to postoperative NIHSS score on 2nd postoperative day, the patients were divided into 3 groups: group A no neurological deficit ( NIHSS score 0-9 );group B mild neurological deficit (NIHSS score 10-19) and group C moderate or severe neurological deficit (NIHSS score 20-45). Blood samples were taken from internal jugular vein before CPB (T0), at 30 min of CPB (T1), at the discontinuation of CPB (T2), and at 1, 6, 24 h after discontinuation of CPB (T3-5) for determination of the plasma MBP concentration. The duration of operation, CPB time, aortic cross-clamping time were recorded.Results In group B the plasma MBP level peaked at 6 h after CPB (T4) and then decreased rapidly while in group C the plasma MBP level exceeded the normal upper limit at T2 and kept increasing till 24 h after CPB (T5 ).The plasma MBP level decreased at T1-3.5 in group A as compared with the normal upper limit. The plasma MBPlevel was significantly higher at T3-5 in group B and at T1-5 in group C than in group A and at T1-5 in group C than in group B. Linear regression analysis indicated that there was positive correlation between plasma MBP level and CPB time at T5. NIHSS scores were positively correlated with plasma MBP level at T1 , T2, and T5. Conclusion MBP can early reflect the severity of brain injury in patients undergoing cardiac surgery under CPB.