Objective To study the effect of electromagnetic pulse （EMP） exposure on permeability of in vitro blood-brain-barrier （BBB） model. Methods An in vitro BBB model, established by co-culturing brain microvascular end...Objective To study the effect of electromagnetic pulse （EMP） exposure on permeability of in vitro blood-brain-barrier （BBB） model. Methods An in vitro BBB model, established by co-culturing brain microvascular endothelial cells （BMVEC） and astroglial cells （AC） isolated from rat brain, was exposed to EMP at 100 kV/m and 400 kV/m, respectively. Permeability of the model was assayed by measuring the transendothelial electrical resistance （TEER） and the horseradish peroxidase （HRP） transmission at different time points. Levels of BBB tight junction-related proteins were measured at O, 1, 2, 4, 8, 12, 16, 20, 24 h after EMP exposure by Western blotting. Results The TEER level was lower in BBB model group than in control group at 12 h after EMP, exposure which returned to its normal level at 24 h. The 24 h recovery process was triphasic and biphasic respectively after EMP exposure at 100 kV/m and 400 kV/m. Following exposure to 400 kV/m EMP, the HRP permeability increased at 1-12 h and returned to its normal level at 24 h. Western blotting showed that the claudin-5 and ZO-1 protein levels were changed after EMP exposure. Conclusion EMP exposure at 100 kV/m and 400 kV/m can increase the permeability of in vitro BBB model and BBB tight junction-related proteins such as ZO-1 and claudin-5 may change EMP-induced BBB permeability.展开更多
目的研究桃红四物汤的抗癫痫作用机制。方法建立戊四氮(PTZ)点燃大鼠癫痫模型,随机分为对照组、模型组和桃红四物汤低、中、高剂量组。桃红四物汤剂量分别为0.7、1.4、2.1 g/kg,给药体积为10 m L/kg,每日ig给药1次,连续给药2周。给药第0...目的研究桃红四物汤的抗癫痫作用机制。方法建立戊四氮(PTZ)点燃大鼠癫痫模型,随机分为对照组、模型组和桃红四物汤低、中、高剂量组。桃红四物汤剂量分别为0.7、1.4、2.1 g/kg,给药体积为10 m L/kg,每日ig给药1次,连续给药2周。给药第0、14天观察大鼠癫痫发作程度。给药结束处死大鼠,伊文思蓝(EB)法测定血脑屏障通透性,Western blotting法和免疫荧光法测定脑组织及不同部位3种紧密连接蛋白:闭锁连接蛋白-1(ZO-1)、基质金属蛋白酶-9(MMP-9)、Occludin蛋白表达水平。结果高、中、低剂量桃红四物汤可显著降低大鼠癫痫发作程度和血脑屏障通透性(P<0.01)。低剂量桃红四物汤可显著升高大鼠脑组织皮层、海马及纹状体的MMP-9表达水平(P<0.05);中、高剂量桃红四物汤可显著升高大鼠脑组织ZO-1、MMP-9、Occludin表达水平(P<0.05、0.01)。结论桃红四物汤可显著减轻癫痫发作程度,作用机制可能与降低血脑屏障通透性及升高脑组织紧密连接蛋白表达水平有关。展开更多
We devoted this short interview piece with Dr Shou-Ching Tang at Augusta University to feature some promising results from a clinical phase II trial on a novel brain-penetrating peptide-paclitaxel-conjugate,ANG1005,in...We devoted this short interview piece with Dr Shou-Ching Tang at Augusta University to feature some promising results from a clinical phase II trial on a novel brain-penetrating peptide-paclitaxel-conjugate,ANG1005,in treating brain metastatic breast cancer.These results were presented by Dr.Tang at the recent annual meeting of the European Society for Medical Oncology(ESMO 2016 Congress).This development heralds an important step forward towards the development of effective chemotherapeutic agents,which can cross the bloodbrain-barrier and effectively treat and prevent the brain metastatic cancers.展开更多
Abstract: Objective To find an effective method for the treatment of malignant cerebral glioma by opening the bloodbrainbarrier (BBB).Methods The concentration of methotrexate (MTX) in tumor was measured in 18 pa...Abstract: Objective To find an effective method for the treatment of malignant cerebral glioma by opening the bloodbrainbarrier (BBB).Methods The concentration of methotrexate (MTX) in tumor was measured in 18 patients with cerebral glioma, and 155 patients with malignant glioma were treated by intracarotid infusion of papaverine and Bischloronitrosourea (BCNU).Results After intracarotid infusion of papaverine for reversible opening of BBB, the MTX concentration in tumor tissue was 1810±380 ng/g, higher than that in patients without papaverine infusion (997±126 ng/g). Eightynine patients with glioblastoma and 66 patients with anaplastic astrocytoma received intracarotid infusion of papaverine and BCNU (250 mg) for an [CM(23*6/8]average of 2.14 times. The mean survival time of thesepatients was 114.5 weeks, median survival time was 140 weeks, and fiveyear survival rate was 22.97%.Conclusion The combined chemotherapy with papaverine and BCNU through intraarterial infusion is simple, safe and effective in treating malignant cerebral glioma so long as the tumor is sensitive to the drugs.展开更多
Rabies is a disease caused following infection of the brainby the rabies virus(RABV). The principle mechanism of transmission is through a bite wound. The virus infects peripheral nerves and moves to the central nervo...Rabies is a disease caused following infection of the brainby the rabies virus(RABV). The principle mechanism of transmission is through a bite wound. The virus infects peripheral nerves and moves to the central nervous system(CNS). There appears to be little involvement of other organ systems and little detectable immune stimulation prior to infection of the CNS. This failure of the mammalian immune system to respond to rabies virus infection leads, in the overwhelming majority of cases, to death of the host. To some extent, this failure is likely due to the exclusive replication of RABV in neurons and the limited ability to generate, sufficiently rapidly, an anti-viral antibody response in situ. This is reflected in the ability of post-exposure vaccination, when given early after infection, to prevent disease. The lack of immune stimulation during RABV infection preceding neural invasion is the Achilles heel of the immune response. Whilst many viruses infect the brain, causing encephalitis and neuronal deficit, none are as consistently fatal to the host as RABV. This is in part due to prior replication of many viruses in peripheral, non-neural tissue by other viruses that allows timely activation of the immune response before the host is overwhelmed. Our current understanding of the correlates of protection for rabies suggests that it is the action of neutralising antibodies that prevent infection and control spread of RABV. Furthermore, it tells us that the induction of immunity can protect and understanding how and why this happens is critical to controlling infection. However, the paradigm of antibody development suggests that antigen presentation overwhelmingly occurs in lymphoid tissue(germinal and non-germinal centres) and these are external to the CNS. In addition, the blood-brain-barrier may provide a block to the delivery of immune effectors(antibodies/plasma B-cells) entering where they are needed. Alternatively, there may be insufficient antigen exposure after natural infection to mount an effective 展开更多
Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS) through demyelination and neurodegeneration. Several lines of evidence support a role for oxidative and nitrative str...Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS) through demyelination and neurodegeneration. Several lines of evidence support a role for oxidative and nitrative stress (OS and NS) in pathogenesis of multiple sclerosis. The mechanism of influence of OS and NS on blood-brainbarrier (BBB) has critical importance for evaluating antioxidant therapies. As far as we know, markers of oxidative and nitrative stress in MS patients have been investigated independently for their relationship with the state of the blood-brain-barrier. Blood plasma samples of 58 patients with relapse-remitting MS (RRMS) with normal (Group A, n = 48, 36.2 ± 10.5 years) and damaged BBB (Group B, n = 10, 38.2 ± 11.2 years) and of 44 healthy controls (39.2 ± 14.9 years) were analyzed. TAS (total antioxidant plasma status), lipoperoxides, protein carbonyls, 3-nitrotyrosine and uric acid were evaluated in each group. Our results confirmed decreased TAS (Group A: 1.35 ± 0.55 mmol/l, P e level of lipoperoxidation positively correlated with the state of BBB (P of protein’s carbonyls (A: 0.48 ± 0.11 nmol/mg protein, P nmol/l, P ed damage to plasma proteins, what was confirmed by their positive mutual correlation (P The level of uric acid was physiological and correlated negatively with protein’s carbonyls (P 0.05) while there was no significant relationship with 3-nitotyrosine. The results suggest the role of this antioxidant in the protection of the proteins against OS what was confirmed by its positive correlation with TAS展开更多
基金supported by the National Basic Research Program of China(2011CB503704,2011CB503705)National Natural Science Foundation of China (No. 30970670, 60871068)
文摘Objective To study the effect of electromagnetic pulse （EMP） exposure on permeability of in vitro blood-brain-barrier （BBB） model. Methods An in vitro BBB model, established by co-culturing brain microvascular endothelial cells （BMVEC） and astroglial cells （AC） isolated from rat brain, was exposed to EMP at 100 kV/m and 400 kV/m, respectively. Permeability of the model was assayed by measuring the transendothelial electrical resistance （TEER） and the horseradish peroxidase （HRP） transmission at different time points. Levels of BBB tight junction-related proteins were measured at O, 1, 2, 4, 8, 12, 16, 20, 24 h after EMP exposure by Western blotting. Results The TEER level was lower in BBB model group than in control group at 12 h after EMP, exposure which returned to its normal level at 24 h. The 24 h recovery process was triphasic and biphasic respectively after EMP exposure at 100 kV/m and 400 kV/m. Following exposure to 400 kV/m EMP, the HRP permeability increased at 1-12 h and returned to its normal level at 24 h. Western blotting showed that the claudin-5 and ZO-1 protein levels were changed after EMP exposure. Conclusion EMP exposure at 100 kV/m and 400 kV/m can increase the permeability of in vitro BBB model and BBB tight junction-related proteins such as ZO-1 and claudin-5 may change EMP-induced BBB permeability.
文摘目的研究桃红四物汤的抗癫痫作用机制。方法建立戊四氮(PTZ)点燃大鼠癫痫模型,随机分为对照组、模型组和桃红四物汤低、中、高剂量组。桃红四物汤剂量分别为0.7、1.4、2.1 g/kg,给药体积为10 m L/kg,每日ig给药1次,连续给药2周。给药第0、14天观察大鼠癫痫发作程度。给药结束处死大鼠,伊文思蓝(EB)法测定血脑屏障通透性,Western blotting法和免疫荧光法测定脑组织及不同部位3种紧密连接蛋白:闭锁连接蛋白-1(ZO-1)、基质金属蛋白酶-9(MMP-9)、Occludin蛋白表达水平。结果高、中、低剂量桃红四物汤可显著降低大鼠癫痫发作程度和血脑屏障通透性(P<0.01)。低剂量桃红四物汤可显著升高大鼠脑组织皮层、海马及纹状体的MMP-9表达水平(P<0.05);中、高剂量桃红四物汤可显著升高大鼠脑组织ZO-1、MMP-9、Occludin表达水平(P<0.05、0.01)。结论桃红四物汤可显著减轻癫痫发作程度,作用机制可能与降低血脑屏障通透性及升高脑组织紧密连接蛋白表达水平有关。
文摘We devoted this short interview piece with Dr Shou-Ching Tang at Augusta University to feature some promising results from a clinical phase II trial on a novel brain-penetrating peptide-paclitaxel-conjugate,ANG1005,in treating brain metastatic breast cancer.These results were presented by Dr.Tang at the recent annual meeting of the European Society for Medical Oncology(ESMO 2016 Congress).This development heralds an important step forward towards the development of effective chemotherapeutic agents,which can cross the bloodbrain-barrier and effectively treat and prevent the brain metastatic cancers.
文摘Abstract: Objective To find an effective method for the treatment of malignant cerebral glioma by opening the bloodbrainbarrier (BBB).Methods The concentration of methotrexate (MTX) in tumor was measured in 18 patients with cerebral glioma, and 155 patients with malignant glioma were treated by intracarotid infusion of papaverine and Bischloronitrosourea (BCNU).Results After intracarotid infusion of papaverine for reversible opening of BBB, the MTX concentration in tumor tissue was 1810±380 ng/g, higher than that in patients without papaverine infusion (997±126 ng/g). Eightynine patients with glioblastoma and 66 patients with anaplastic astrocytoma received intracarotid infusion of papaverine and BCNU (250 mg) for an [CM(23*6/8]average of 2.14 times. The mean survival time of thesepatients was 114.5 weeks, median survival time was 140 weeks, and fiveyear survival rate was 22.97%.Conclusion The combined chemotherapy with papaverine and BCNU through intraarterial infusion is simple, safe and effective in treating malignant cerebral glioma so long as the tumor is sensitive to the drugs.
基金Supported by The European Union Seventh Framework Programme through project ANTIGONE:Anticipating the global onset of novel epidemics,No.278976
文摘Rabies is a disease caused following infection of the brainby the rabies virus(RABV). The principle mechanism of transmission is through a bite wound. The virus infects peripheral nerves and moves to the central nervous system(CNS). There appears to be little involvement of other organ systems and little detectable immune stimulation prior to infection of the CNS. This failure of the mammalian immune system to respond to rabies virus infection leads, in the overwhelming majority of cases, to death of the host. To some extent, this failure is likely due to the exclusive replication of RABV in neurons and the limited ability to generate, sufficiently rapidly, an anti-viral antibody response in situ. This is reflected in the ability of post-exposure vaccination, when given early after infection, to prevent disease. The lack of immune stimulation during RABV infection preceding neural invasion is the Achilles heel of the immune response. Whilst many viruses infect the brain, causing encephalitis and neuronal deficit, none are as consistently fatal to the host as RABV. This is in part due to prior replication of many viruses in peripheral, non-neural tissue by other viruses that allows timely activation of the immune response before the host is overwhelmed. Our current understanding of the correlates of protection for rabies suggests that it is the action of neutralising antibodies that prevent infection and control spread of RABV. Furthermore, it tells us that the induction of immunity can protect and understanding how and why this happens is critical to controlling infection. However, the paradigm of antibody development suggests that antigen presentation overwhelmingly occurs in lymphoid tissue(germinal and non-germinal centres) and these are external to the CNS. In addition, the blood-brain-barrier may provide a block to the delivery of immune effectors(antibodies/plasma B-cells) entering where they are needed. Alternatively, there may be insufficient antigen exposure after natural infection to mount an effective
文摘Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS) through demyelination and neurodegeneration. Several lines of evidence support a role for oxidative and nitrative stress (OS and NS) in pathogenesis of multiple sclerosis. The mechanism of influence of OS and NS on blood-brainbarrier (BBB) has critical importance for evaluating antioxidant therapies. As far as we know, markers of oxidative and nitrative stress in MS patients have been investigated independently for their relationship with the state of the blood-brain-barrier. Blood plasma samples of 58 patients with relapse-remitting MS (RRMS) with normal (Group A, n = 48, 36.2 ± 10.5 years) and damaged BBB (Group B, n = 10, 38.2 ± 11.2 years) and of 44 healthy controls (39.2 ± 14.9 years) were analyzed. TAS (total antioxidant plasma status), lipoperoxides, protein carbonyls, 3-nitrotyrosine and uric acid were evaluated in each group. Our results confirmed decreased TAS (Group A: 1.35 ± 0.55 mmol/l, P e level of lipoperoxidation positively correlated with the state of BBB (P of protein’s carbonyls (A: 0.48 ± 0.11 nmol/mg protein, P nmol/l, P ed damage to plasma proteins, what was confirmed by their positive mutual correlation (P The level of uric acid was physiological and correlated negatively with protein’s carbonyls (P 0.05) while there was no significant relationship with 3-nitotyrosine. The results suggest the role of this antioxidant in the protection of the proteins against OS what was confirmed by its positive correlation with TAS
