BACKGROUND: Acupuncture treatment on injured cerebral axons has shown to provide efficacy in clinical practice. It is unknown whether acupuncture produces therapeutic effects by protecting injured cerebral myelin in ...BACKGROUND: Acupuncture treatment on injured cerebral axons has shown to provide efficacy in clinical practice. It is unknown whether acupuncture produces therapeutic effects by protecting injured cerebral myelin in ischemic stroke. OBJECTIVE: To test whether acupuncture provides protection for injured cerebral myelin, based on quantitative data from cerebral ischemia-reperfusion rats, and to compare the effects of early and late acupuncture on serum myelin basic protein (MBP) content and remyelination of the ischemic internal capsule.DESIGN, TIME AND SETTING: A randomized, controlled experiment was performed at the Neurobiological Laboratory, Sichuan University from March 2005 to March 2006. MATERIALS: "Hua Tuo" Brand filiform needles were produced by the Medical Instrument Factory of Suzhou, China.METHODS: A total of 52 adult, healthy, male, Sprague Dawley rats were randomly assigned to four groups: control (n = 4), model (n = 16), early acupuncture (n = 16), and late acupuncture (n = 16). The focal cerebral ischemia-reperfusion model was established by middle cerebral artery occlusion in the right hemisphere using the modified thread embolism method in the latter three groups. Early and late acupuncture groups underwent acupuncture after ischemia for 30 minutes and 2 hours using the Xingnaokaiqiao needling method, respectively. Acupoints were "Neiguarf' (PC 6) and "Sanyinjiao" (SP 6) on the bilateral sides, as well as "Shuigou' (DU 26) and "Baihui" (DU 20) with stimulation for 1 minute at each acupoint. Acupuncture at all acupoints was performed two or three times while the needle was retained, once per day. No special handling was administered to the control clroup.MAIN OUTCOME MEASURES: For each group, remyelination of the internal capsule was observed by Pal-Weigert's myelin staining and serum MBP content was detected using enzyme-linked immunosorbent assay method on days 1,3, 5, and 7 following ischemia-reperfusion injury.RESULTS: Compared with the control group, massive demyelination of the internal capsule occurred, and serum MBP content increased in the model group (P 〈 0.05). Compared with the model group, the extent of demyelination in the internal capsule was less distinct and serum MBP content was significantly less in the early and late acupuncture group (P 〈 0.01 ). Compared with the late acupuncture group, serum MBP content reached a peak later and the peak value was less in the early acupuncture group. CONCLUSION: Results suggest that acupuncture exerts a protective effect on injured cerebral myelin in ischemia-reperfusion rats by reducing serum MBP content and promoting remyelination. The study also suggests that the effect of early acupuncture is superior to late acupuncture.展开更多
In order to study whether patients with schizophrenia have cerebral injury, neuron-specific enolase (NSE) and myelin basic protein (MBP)in cerebrospinal fluid (CSF) of 33 patients with first episode schizophreni...In order to study whether patients with schizophrenia have cerebral injury, neuron-specific enolase (NSE) and myelin basic protein (MBP)in cerebrospinal fluid (CSF) of 33 patients with first episode schizophrenia and 9 from the control group were determined by double antibody sandwich enzyme immunoassay method. The results showed that there was significant difference in the NSE contents between the experimental group and control group (P〈0.01). The NSE contents in CSF in the experimental group were positively correlated with MBP in schizophrenia patients (P〈 0.05). These findings suggested that patients with schizophrenia had cerebral injury.展开更多
Myelin basic protein(MBP) is an essential structure involved in the generation of central nervous system(CNS)myelin.Myelin shape has been described as liquid crystal structure of biological membrane.The interactio...Myelin basic protein(MBP) is an essential structure involved in the generation of central nervous system(CNS)myelin.Myelin shape has been described as liquid crystal structure of biological membrane.The interactions of MBP with monolayers of different lipid compositions are responsible for the multi-lamellar structure and stability of myelin.In this paper,we have designed MBP-incorporated model lipid monolayers and studied the phase behavior of MBP adsorbed on the plasma membrane at the air/water interface by thermodynamic method and atomic force microscopy(AFM).By analyzing the pressure–area(π–A) and pressure–time(π–T) isotherms,univariate linear regression equation was obtained.In addition,the elastic modulus,surface pressure increase,maximal insertion pressure,and synergy factor of monolayers were detected.These parameters can be used to modulate the monolayers binding of protein,and the results show that MBP has the strongest affinity for 1,2-dipalmitoyl-sn-glycero-3-phosphoserine(DPPS) monolayer,followed by DPPC/DPPS mixed and1,2-dipalmitoyl-sn-glycero-3-phospho-choline(DPPC) monolayers via electrostatic and hydrophobic interactions.AFM images of DPPS and DPPC/DPPS mixed monolayers in the presence of MBP(5 n M) show a phase separation texture at the surface pressure of 20 m N/m and the incorporation of MBP put into the DPPC monolayers has exerted a significant effect on the domain structure.MBP is not an integral membrane protein but,due to its positive charge,interacts with the lipid head groups and stabilizes the membranes.The interaction between MBP and phospholipid membrane to determine the nervous system of the disease has a good biophysical significance and medical value.展开更多
BACKGROUND: Dithiocarbamates can cause demyelination of axons in the peripheral nervous system. Its derivate, diethyldithiocarbamate, is cytotoxic, and causes olfactory mucosal damage and atrophy of the olfactory bul...BACKGROUND: Dithiocarbamates can cause demyelination of axons in the peripheral nervous system. Its derivate, diethyldithiocarbamate, is cytotoxic, and causes olfactory mucosal damage and atrophy of the olfactory bulb. However, it is still unclear whether the myelin sheath of the lateral olfactory tract is affected by diethyldithiocarbamate. OBJECTIVE: To investigate the effects of diethyldithiocarbamate on the myelin sheath of the rat lateral olfactory tract. This was done by examining changes in myelin basic protein expression after diethyldithiocarbamate treatment. DESIGN, TIME AND SETTING: A randomized, controlled, animal study was performed at the Laboratory of the Department of Human Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, China from July to November 2007. MATERIALS: A total of 72 Sprague Dawley rats were randomly assigned into a diethyldithiocarbamate group (n = 32), a solvent control group (n = 32), and a blank control group (n = 8). The diethyldithiocarbamate and solvent control groups were separately divided into 3-d, 7-d, 14-d and 28-d survival subgroups, with eight rats in each. Diethyldithiocarbamate (Sigma, USA) and goat anti-myelin basic protein polyclonal antibody (Santa Cruz, USA) were used in this study. METHODS: Rats in the diethyldithiocarbamate and solvent control groups were subcutaneously injected with diethyldithiocarbamate (600 mg/kg) and 0.01 mol/L phosphate buffered saline (600 mg/kg) at the posterior neck, respectively. Rats in the blank control group received no treatment. MAIN OUTCOME MEASURES: Immunohistochemical staining and Western blot assay were used to measure myelin basic protein expression in the rat lateral olfactory tract. RESULTS: Following immunohistochemical staining, myelin basic protein was uniformly distributed in the rat lateral olfactory tract in the blank control and solvent control groups. Western blot assay showed 21.5, 18, 17 and 14 ku positive bands. No significant difference was found in myelin basic protein distribution and blot pattern, in the rat lateral olfactory tract, in the diethyldithiocarbamate group, following immunohistochemical staining and Western blot assay. Myelin basic protein expression gradually decreased at day 3, reached the lowest level at day 7, and gradually increased again at days 14 and 28. CONCLUSION: Demyelination is induced by diethyldithiocarbamate in the rat lateral olfactory tract in an early stage, followed by remyelination at later stages.展开更多
Objective In order to determine serum myelin basic protein (MBP) in patients with severe acute pancreatitis and evaluate its clinical significance. Methods\ Serum MBP was measured in 20 patients with acute hemorrhagi...Objective In order to determine serum myelin basic protein (MBP) in patients with severe acute pancreatitis and evaluate its clinical significance. Methods\ Serum MBP was measured in 20 patients with acute hemorrhagic necrotic pancreatitis (AHNP) and in 20 normal subjects by enzyme linked immunoabsorbent assay. Results\ Serum MBP content of AHNP group was significantly higher than that of normal control group (P<0.05). Serum MBP content in patients with pancreatic encephalopathy (PE) was significantly higher than that of those without PE (P<0.05). Conclusion\ ①Serum MBP content in patients with AHNP increased significantly;②Serum MBP content may reflect brain injury and its severity;③The prognosis of AHNP is correlated with its serum MBP content.\;展开更多
Objective: To investigate the therapeutic effect of nerve growth factor (NGF) on changes of myelin basic protein (MBP) and functional repair of sensory and motor nerve following sciatic nerve injury. Methods: The scia...Objective: To investigate the therapeutic effect of nerve growth factor (NGF) on changes of myelin basic protein (MBP) and functional repair of sensory and motor nerve following sciatic nerve injury. Methods: The sciatic nerves of rats were injured by sectioning with shaver,and divided into 3 groups: NGF group (Group A), group of normal saline solution (Group B), untreated group (Group C). The time point of observation was at the 4th week after operation. Sensory evoked potential (SEP) and motor evoked potential (MEP) were detected by Model WD 4000 nerve potential working diagnosis system. Immunohistochemical analysis was used for identification of MBP.Results: The latency of SEP in the Group A at the 4th week after operation was shorter than that in the Group B (P< 0.05 ). The MEP was elicited in 76% of the Group A and was higher than that in the Group B. Results of immunohistochemistry showed that there were less MBP positive cells in the Group A than in the Group B in one and four weeks respectively.Conclusions: NGF can improve the conductive function of injured peripheral nerve and facilitate regeneration of nerve.展开更多
Background: The interaction between activated microglia and T lymphocytes can yield abundant pro-inflammatory cytokines. Our previous study proved that thymus immune tolerance could alleviate the inflammatory respons...Background: The interaction between activated microglia and T lymphocytes can yield abundant pro-inflammatory cytokines. Our previous study proved that thymus immune tolerance could alleviate the inflammatory response. This study aimed to investigate whether intrathymic injection of myelin basic protein (MBP) in mice could suppress the inflammatory response after co-culture ofT lymphocytes and BV-2 microglia cells. Methods: Totally, 72 male C57BL/6 mice were randomly assigned to three groups (17 - 24 in each): Group A: intrathymic injection of 100 μl M BP (1 mg/ml); Group B: intrathymic injection of 100 μ1 phosphate-buffered saline (PBS); and Group C: sham operation group. Every eight mice in each group were sacrificed to obtain the spleen at postoperative days 3, 7, and 14, respectively. T lymphocytes those were extracted and purified from the spleens were then co-cultured with activated BV-2 microglia cells at a proportion of 1:2 in the medium containing MBP for 3 days. After identified the T lymphocytes by CD3, surface antigens oft lymphocytes (CD4, CD8, CD152, and CD154) and BV-2 microglia cells (CD45 and CD54) were detected by flow cytometry. The expressions of pro-inflammatory factors of BV-2 microglia cells (interleukin [1L]- 1β, tumor necrosis factor-o~ [TNF-α], and inducible nitric oxide synthase [iNOS]) were detected by quantitative real-time polymerase chain reaction (PCR). One-way analysis of variance (ANOVA) and the least significant difference test were used for data analysis. Results: The levels of CD152 in Group A showed an upward trend from the 3rd to 7th day, with a downward trend from the 7th to 14th day (20.12 ± 0.71%, 30.71 ± 1.14%, 13.50 ± 0.71% at postoperative days 3, 7, and 14, respectively, P 〈 0.05). The levels of CD 154 in Group A showed a downward trend from the 3ra to 7th day, with an upward trend from the 7th to 14th day (1 0.00± 0.23%, 5.28 ±0.69%, 14.67 ± 2.71% at postoperative days 3, 7, and 14, respectively, P 〈 0.05). The ratio ofCD4+/CD8 + T in Group A showed a downward trend from the 3rd to 7th day, with the minimum at postoperative day 7, then an upward trend from the 7th to 14th day (P 〈 0.05). Meanwhile, the levels of CD45 and CD54 in Group A were found as the same trend as the ratio of CD4+/CD8 + T (CD45:83.39 ± 2.56%, 82.74± 2.09%, 87.56 ± 2. 11%: CD54:3.80 ± 0.24%, 0.94 ± 0.40%, 3.41 ± 0.33% at postoperative days 3, 7, and 14, respectively, P 〈 0.05). The expressions of TNF-α, IL- 1 β, and iNOS in Group A were significantly lower than those in Groups B and C, and the values at postoperative day 7 were the lowest compared with those at postoperative days 3 and 14 (P 〈 0.05). No significant difference was found between Groups B and C. Conclusions: l ntrathymic injection of MBP could suppress the immune reaction that might reduce the secondary immune injury of brain tissue induced by an inflammatory response.展开更多
A thermodynamic study on the interaction of myelin basic protein with mercury ion was studied by using isothermal titration calonmetry,ITC,at 300.15,310.15 and 320.15 K in Tris buffer solution at pH 7.The enthalpies o...A thermodynamic study on the interaction of myelin basic protein with mercury ion was studied by using isothermal titration calonmetry,ITC,at 300.15,310.15 and 320.15 K in Tris buffer solution at pH 7.The enthalpies of MBP + Hg^(2+) interaction are reported and analysed in terms of the extended solvation model.It was found that MBP has two identical and non-cooperative binding sites for Hg^(2+) ions.The intrinsic dissociation equilibrium constants are 99.904,112.968 and 126.724μmol/L,and the molar enthalpy of binding are -11.634,-10.768 and -10.117kJ mol^(-1) at 300.15,310.15 and 320.15 K,respectively.展开更多
Piezo1 is a mechanically-gated calcium channel.Recent studies have shown that Piezo1,a mechanically-gated calcium channel,can attenuate both psychosineand lipopolysaccharide-induced demyelination.Because oligodendrocy...Piezo1 is a mechanically-gated calcium channel.Recent studies have shown that Piezo1,a mechanically-gated calcium channel,can attenuate both psychosineand lipopolysaccharide-induced demyelination.Because oligodendrocyte damage and demyelination occur in intracerebral hemorrhage,in this study,we investigated the role of Piezo1 in intracerebral hemorrhage.We established a mouse model of cerebral hemorrhage by injecting autologous blood into the right basal ganglia and found that Piezo1 was largely expressed soon(within 48 hours)after intracerebral hemorrhage,primarily in oligodendrocytes.Intraperitoneal injection of Dooku1 to inhibit Piezo1 resulted in marked alleviation of brain edema,myelin sheath loss,and degeneration in injured tissue,a substantial reduction in oligodendrocyte apoptosis,and a significant improvement in neurological function.In addition,we found that Dooku1-mediated Piezo1 suppression reduced intracellular endoplasmic reticulum stress and cell apoptosis through the PERK-ATF4-CHOP and inositol-requiring enzyme 1 signaling pathway.These findings suggest that Piezo1 is a potential therapeutic target for intracerebral hemorrhage,as its suppression reduces intracellular endoplasmic reticulum stress and cell apoptosis and protects the myelin sheath,thereby improving neuronal function after intracerebral hemorrhage.展开更多
The APPSwe/PSEN1 dE9(APP/PS1) transgenic mouse model is an Alzheimer's disease mouse model exhibiting symptoms of dementia, and is commonly used to explore pathological changes in the development of Alzheimer's di...The APPSwe/PSEN1 dE9(APP/PS1) transgenic mouse model is an Alzheimer's disease mouse model exhibiting symptoms of dementia, and is commonly used to explore pathological changes in the development of Alzheimer's disease. Previous clinical autopsy and imaging studies suggest that Alzheimer's disease patients have white matter and oligodendrocyte damage, but the underlying mechanisms of these have not been revealed. Therefore, the present study used APP/PS1 mice to assess cognitive change, myelin loss, and corresponding changes in oligodendrocytes, and to explore the underlying mechanisms. Morris water maze tests were performed to evaluate cognitive change in APP/PS1 mice and normal C57 BL/6 mice aged 3 and 6 months. Luxol fast blue staining of the corpus callosum and quantitative reverse transcription-polymerase chain reaction(q RT-PCR) for myelin basic protein(MBP) mRNA were carried out to quantify myelin damage. Immunohistochemistry staining for NG2 and qRT-PCR for monocarboxylic acid transporter 1(MCT1) mRNA were conducted to assess corresponding changes in oligodendrocytes. Our results demonstrate that compared with C57 BL/6 mice, there was a downregulation of MBP mRNA in APP/PS1 mice aged 3 months. This became more obvious in APP/PS1 mice aged 6 months accompanied by other abnormalities such as prolonged escape latency in the Morris water maze test, shrinkage of the corpus callosum, upregulation of NG2-immunoreactive cells, and downregulation of MCT1 mRNA. These findings indicate that the involvement of early demyelination at 3 months and the oligodendrocyte dysfunction at 6 months in APP/PS1 mice are in association with Alzheimer's disease pathogenesis.展开更多
文摘BACKGROUND: Acupuncture treatment on injured cerebral axons has shown to provide efficacy in clinical practice. It is unknown whether acupuncture produces therapeutic effects by protecting injured cerebral myelin in ischemic stroke. OBJECTIVE: To test whether acupuncture provides protection for injured cerebral myelin, based on quantitative data from cerebral ischemia-reperfusion rats, and to compare the effects of early and late acupuncture on serum myelin basic protein (MBP) content and remyelination of the ischemic internal capsule.DESIGN, TIME AND SETTING: A randomized, controlled experiment was performed at the Neurobiological Laboratory, Sichuan University from March 2005 to March 2006. MATERIALS: "Hua Tuo" Brand filiform needles were produced by the Medical Instrument Factory of Suzhou, China.METHODS: A total of 52 adult, healthy, male, Sprague Dawley rats were randomly assigned to four groups: control (n = 4), model (n = 16), early acupuncture (n = 16), and late acupuncture (n = 16). The focal cerebral ischemia-reperfusion model was established by middle cerebral artery occlusion in the right hemisphere using the modified thread embolism method in the latter three groups. Early and late acupuncture groups underwent acupuncture after ischemia for 30 minutes and 2 hours using the Xingnaokaiqiao needling method, respectively. Acupoints were "Neiguarf' (PC 6) and "Sanyinjiao" (SP 6) on the bilateral sides, as well as "Shuigou' (DU 26) and "Baihui" (DU 20) with stimulation for 1 minute at each acupoint. Acupuncture at all acupoints was performed two or three times while the needle was retained, once per day. No special handling was administered to the control clroup.MAIN OUTCOME MEASURES: For each group, remyelination of the internal capsule was observed by Pal-Weigert's myelin staining and serum MBP content was detected using enzyme-linked immunosorbent assay method on days 1,3, 5, and 7 following ischemia-reperfusion injury.RESULTS: Compared with the control group, massive demyelination of the internal capsule occurred, and serum MBP content increased in the model group (P 〈 0.05). Compared with the model group, the extent of demyelination in the internal capsule was less distinct and serum MBP content was significantly less in the early and late acupuncture group (P 〈 0.01 ). Compared with the late acupuncture group, serum MBP content reached a peak later and the peak value was less in the early acupuncture group. CONCLUSION: Results suggest that acupuncture exerts a protective effect on injured cerebral myelin in ischemia-reperfusion rats by reducing serum MBP content and promoting remyelination. The study also suggests that the effect of early acupuncture is superior to late acupuncture.
文摘In order to study whether patients with schizophrenia have cerebral injury, neuron-specific enolase (NSE) and myelin basic protein (MBP)in cerebrospinal fluid (CSF) of 33 patients with first episode schizophrenia and 9 from the control group were determined by double antibody sandwich enzyme immunoassay method. The results showed that there was significant difference in the NSE contents between the experimental group and control group (P〈0.01). The NSE contents in CSF in the experimental group were positively correlated with MBP in schizophrenia patients (P〈 0.05). These findings suggested that patients with schizophrenia had cerebral injury.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.21402114 and 11544009)the Natural Science Basic Research Plan in Shaanxi Province of China(Grant No.2016JM2010)+1 种基金the Fundamental Research Funds for the Central Universities of China(Grant No.GK201604004)the National University Science and Technology Innovation Project of China(Grant Nos.201610718014 and cx16018)
文摘Myelin basic protein(MBP) is an essential structure involved in the generation of central nervous system(CNS)myelin.Myelin shape has been described as liquid crystal structure of biological membrane.The interactions of MBP with monolayers of different lipid compositions are responsible for the multi-lamellar structure and stability of myelin.In this paper,we have designed MBP-incorporated model lipid monolayers and studied the phase behavior of MBP adsorbed on the plasma membrane at the air/water interface by thermodynamic method and atomic force microscopy(AFM).By analyzing the pressure–area(π–A) and pressure–time(π–T) isotherms,univariate linear regression equation was obtained.In addition,the elastic modulus,surface pressure increase,maximal insertion pressure,and synergy factor of monolayers were detected.These parameters can be used to modulate the monolayers binding of protein,and the results show that MBP has the strongest affinity for 1,2-dipalmitoyl-sn-glycero-3-phosphoserine(DPPS) monolayer,followed by DPPC/DPPS mixed and1,2-dipalmitoyl-sn-glycero-3-phospho-choline(DPPC) monolayers via electrostatic and hydrophobic interactions.AFM images of DPPS and DPPC/DPPS mixed monolayers in the presence of MBP(5 n M) show a phase separation texture at the surface pressure of 20 m N/m and the incorporation of MBP put into the DPPC monolayers has exerted a significant effect on the domain structure.MBP is not an integral membrane protein but,due to its positive charge,interacts with the lipid head groups and stabilizes the membranes.The interaction between MBP and phospholipid membrane to determine the nervous system of the disease has a good biophysical significance and medical value.
基金Supported by:the National Natural Science Foundation of China,No.30600224Supported by:the National Natural Science Foundation of China,No.30700438+2 种基金the Postdoctoral Foundation of China,No.20060390886Hunan Province Natural Science Foundation,No.07JJ5026Hunan Province Scientific Program,No.2008FJ3138
文摘BACKGROUND: Dithiocarbamates can cause demyelination of axons in the peripheral nervous system. Its derivate, diethyldithiocarbamate, is cytotoxic, and causes olfactory mucosal damage and atrophy of the olfactory bulb. However, it is still unclear whether the myelin sheath of the lateral olfactory tract is affected by diethyldithiocarbamate. OBJECTIVE: To investigate the effects of diethyldithiocarbamate on the myelin sheath of the rat lateral olfactory tract. This was done by examining changes in myelin basic protein expression after diethyldithiocarbamate treatment. DESIGN, TIME AND SETTING: A randomized, controlled, animal study was performed at the Laboratory of the Department of Human Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, China from July to November 2007. MATERIALS: A total of 72 Sprague Dawley rats were randomly assigned into a diethyldithiocarbamate group (n = 32), a solvent control group (n = 32), and a blank control group (n = 8). The diethyldithiocarbamate and solvent control groups were separately divided into 3-d, 7-d, 14-d and 28-d survival subgroups, with eight rats in each. Diethyldithiocarbamate (Sigma, USA) and goat anti-myelin basic protein polyclonal antibody (Santa Cruz, USA) were used in this study. METHODS: Rats in the diethyldithiocarbamate and solvent control groups were subcutaneously injected with diethyldithiocarbamate (600 mg/kg) and 0.01 mol/L phosphate buffered saline (600 mg/kg) at the posterior neck, respectively. Rats in the blank control group received no treatment. MAIN OUTCOME MEASURES: Immunohistochemical staining and Western blot assay were used to measure myelin basic protein expression in the rat lateral olfactory tract. RESULTS: Following immunohistochemical staining, myelin basic protein was uniformly distributed in the rat lateral olfactory tract in the blank control and solvent control groups. Western blot assay showed 21.5, 18, 17 and 14 ku positive bands. No significant difference was found in myelin basic protein distribution and blot pattern, in the rat lateral olfactory tract, in the diethyldithiocarbamate group, following immunohistochemical staining and Western blot assay. Myelin basic protein expression gradually decreased at day 3, reached the lowest level at day 7, and gradually increased again at days 14 and 28. CONCLUSION: Demyelination is induced by diethyldithiocarbamate in the rat lateral olfactory tract in an early stage, followed by remyelination at later stages.
文摘Objective In order to determine serum myelin basic protein (MBP) in patients with severe acute pancreatitis and evaluate its clinical significance. Methods\ Serum MBP was measured in 20 patients with acute hemorrhagic necrotic pancreatitis (AHNP) and in 20 normal subjects by enzyme linked immunoabsorbent assay. Results\ Serum MBP content of AHNP group was significantly higher than that of normal control group (P<0.05). Serum MBP content in patients with pancreatic encephalopathy (PE) was significantly higher than that of those without PE (P<0.05). Conclusion\ ①Serum MBP content in patients with AHNP increased significantly;②Serum MBP content may reflect brain injury and its severity;③The prognosis of AHNP is correlated with its serum MBP content.\;
基金ThisworkwassupportedbytheMajorStateBasicResearchDevelopmentProgramofChina (No .G19990 5 42 0 6 )
文摘Objective: To investigate the therapeutic effect of nerve growth factor (NGF) on changes of myelin basic protein (MBP) and functional repair of sensory and motor nerve following sciatic nerve injury. Methods: The sciatic nerves of rats were injured by sectioning with shaver,and divided into 3 groups: NGF group (Group A), group of normal saline solution (Group B), untreated group (Group C). The time point of observation was at the 4th week after operation. Sensory evoked potential (SEP) and motor evoked potential (MEP) were detected by Model WD 4000 nerve potential working diagnosis system. Immunohistochemical analysis was used for identification of MBP.Results: The latency of SEP in the Group A at the 4th week after operation was shorter than that in the Group B (P< 0.05 ). The MEP was elicited in 76% of the Group A and was higher than that in the Group B. Results of immunohistochemistry showed that there were less MBP positive cells in the Group A than in the Group B in one and four weeks respectively.Conclusions: NGF can improve the conductive function of injured peripheral nerve and facilitate regeneration of nerve.
文摘Background: The interaction between activated microglia and T lymphocytes can yield abundant pro-inflammatory cytokines. Our previous study proved that thymus immune tolerance could alleviate the inflammatory response. This study aimed to investigate whether intrathymic injection of myelin basic protein (MBP) in mice could suppress the inflammatory response after co-culture ofT lymphocytes and BV-2 microglia cells. Methods: Totally, 72 male C57BL/6 mice were randomly assigned to three groups (17 - 24 in each): Group A: intrathymic injection of 100 μl M BP (1 mg/ml); Group B: intrathymic injection of 100 μ1 phosphate-buffered saline (PBS); and Group C: sham operation group. Every eight mice in each group were sacrificed to obtain the spleen at postoperative days 3, 7, and 14, respectively. T lymphocytes those were extracted and purified from the spleens were then co-cultured with activated BV-2 microglia cells at a proportion of 1:2 in the medium containing MBP for 3 days. After identified the T lymphocytes by CD3, surface antigens oft lymphocytes (CD4, CD8, CD152, and CD154) and BV-2 microglia cells (CD45 and CD54) were detected by flow cytometry. The expressions of pro-inflammatory factors of BV-2 microglia cells (interleukin [1L]- 1β, tumor necrosis factor-o~ [TNF-α], and inducible nitric oxide synthase [iNOS]) were detected by quantitative real-time polymerase chain reaction (PCR). One-way analysis of variance (ANOVA) and the least significant difference test were used for data analysis. Results: The levels of CD152 in Group A showed an upward trend from the 3rd to 7th day, with a downward trend from the 7th to 14th day (20.12 ± 0.71%, 30.71 ± 1.14%, 13.50 ± 0.71% at postoperative days 3, 7, and 14, respectively, P 〈 0.05). The levels of CD 154 in Group A showed a downward trend from the 3ra to 7th day, with an upward trend from the 7th to 14th day (1 0.00± 0.23%, 5.28 ±0.69%, 14.67 ± 2.71% at postoperative days 3, 7, and 14, respectively, P 〈 0.05). The ratio ofCD4+/CD8 + T in Group A showed a downward trend from the 3rd to 7th day, with the minimum at postoperative day 7, then an upward trend from the 7th to 14th day (P 〈 0.05). Meanwhile, the levels of CD45 and CD54 in Group A were found as the same trend as the ratio of CD4+/CD8 + T (CD45:83.39 ± 2.56%, 82.74± 2.09%, 87.56 ± 2. 11%: CD54:3.80 ± 0.24%, 0.94 ± 0.40%, 3.41 ± 0.33% at postoperative days 3, 7, and 14, respectively, P 〈 0.05). The expressions of TNF-α, IL- 1 β, and iNOS in Group A were significantly lower than those in Groups B and C, and the values at postoperative day 7 were the lowest compared with those at postoperative days 3 and 14 (P 〈 0.05). No significant difference was found between Groups B and C. Conclusions: l ntrathymic injection of MBP could suppress the immune reaction that might reduce the secondary immune injury of brain tissue induced by an inflammatory response.
文摘A thermodynamic study on the interaction of myelin basic protein with mercury ion was studied by using isothermal titration calonmetry,ITC,at 300.15,310.15 and 320.15 K in Tris buffer solution at pH 7.The enthalpies of MBP + Hg^(2+) interaction are reported and analysed in terms of the extended solvation model.It was found that MBP has two identical and non-cooperative binding sites for Hg^(2+) ions.The intrinsic dissociation equilibrium constants are 99.904,112.968 and 126.724μmol/L,and the molar enthalpy of binding are -11.634,-10.768 and -10.117kJ mol^(-1) at 300.15,310.15 and 320.15 K,respectively.
基金supported by the National Natural Science Foundation of China,Nos.81901193(to HLZ)and 81901267(to YY)。
文摘Piezo1 is a mechanically-gated calcium channel.Recent studies have shown that Piezo1,a mechanically-gated calcium channel,can attenuate both psychosineand lipopolysaccharide-induced demyelination.Because oligodendrocyte damage and demyelination occur in intracerebral hemorrhage,in this study,we investigated the role of Piezo1 in intracerebral hemorrhage.We established a mouse model of cerebral hemorrhage by injecting autologous blood into the right basal ganglia and found that Piezo1 was largely expressed soon(within 48 hours)after intracerebral hemorrhage,primarily in oligodendrocytes.Intraperitoneal injection of Dooku1 to inhibit Piezo1 resulted in marked alleviation of brain edema,myelin sheath loss,and degeneration in injured tissue,a substantial reduction in oligodendrocyte apoptosis,and a significant improvement in neurological function.In addition,we found that Dooku1-mediated Piezo1 suppression reduced intracellular endoplasmic reticulum stress and cell apoptosis through the PERK-ATF4-CHOP and inositol-requiring enzyme 1 signaling pathway.These findings suggest that Piezo1 is a potential therapeutic target for intracerebral hemorrhage,as its suppression reduces intracellular endoplasmic reticulum stress and cell apoptosis and protects the myelin sheath,thereby improving neuronal function after intracerebral hemorrhage.
基金supported by the National Natural Science Foundation of China,No.81371395the Liaoning Scientific and Technological Preferential Finance for Returned Overseas 2015 of China,No.[2015]125+2 种基金the Natural Science Foundation of Liaoning Province of China,No.20170541021,2015020547a grant from the Shenyang Science Technology Project,No.F16-206-9-12the China Post-doctoral Science Foundation,No.2015M581375
文摘The APPSwe/PSEN1 dE9(APP/PS1) transgenic mouse model is an Alzheimer's disease mouse model exhibiting symptoms of dementia, and is commonly used to explore pathological changes in the development of Alzheimer's disease. Previous clinical autopsy and imaging studies suggest that Alzheimer's disease patients have white matter and oligodendrocyte damage, but the underlying mechanisms of these have not been revealed. Therefore, the present study used APP/PS1 mice to assess cognitive change, myelin loss, and corresponding changes in oligodendrocytes, and to explore the underlying mechanisms. Morris water maze tests were performed to evaluate cognitive change in APP/PS1 mice and normal C57 BL/6 mice aged 3 and 6 months. Luxol fast blue staining of the corpus callosum and quantitative reverse transcription-polymerase chain reaction(q RT-PCR) for myelin basic protein(MBP) mRNA were carried out to quantify myelin damage. Immunohistochemistry staining for NG2 and qRT-PCR for monocarboxylic acid transporter 1(MCT1) mRNA were conducted to assess corresponding changes in oligodendrocytes. Our results demonstrate that compared with C57 BL/6 mice, there was a downregulation of MBP mRNA in APP/PS1 mice aged 3 months. This became more obvious in APP/PS1 mice aged 6 months accompanied by other abnormalities such as prolonged escape latency in the Morris water maze test, shrinkage of the corpus callosum, upregulation of NG2-immunoreactive cells, and downregulation of MCT1 mRNA. These findings indicate that the involvement of early demyelination at 3 months and the oligodendrocyte dysfunction at 6 months in APP/PS1 mice are in association with Alzheimer's disease pathogenesis.