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Detrimental Effect of Electromagnetic Pulse Exposure on Permeability of In Vitro blood-brain-barrier Model

Biomedical and Environmental Sciences 2013年第2期26卷 128-137页

作者： ZHOU Jia Xing DING Gui Rong ZHANG Jie ZHOU Yong Chun ZHANG Yan Jun GUO Guo Zhen Department of Radiation Medicine Preventive Medicine CollegeFourth Military Medical University

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.

关键词： Electromagnetic pulse blood-brain-barrier Permeability TEER HRP ZO-1 Claudin-5

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Opening blood-brain-barrier by intracarotid infusion of papaverine in treatment of malignant cerebral glioma

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Chinese Medical Journal 1998年第8期 79-81页

作者：薛洪利王辉孔令权周怀伟

Abstract: Objective To find an effective method for the treatment of malignant cerebral glioma by opening the bloodbrainbarrier (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 Bischloronitrosourea (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). Eightynine 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 thesepatients was 114.5 weeks, median survival time was 140 weeks, and fiveyear survival rate was 22.97%.Conclusion The combined chemotherapy with papaverine and BCNU through intraarterial infusion is simple, safe and effective in treating malignant cerebral glioma so long as the tumor is sensitive to the drugs.

关键词： infusion papaverine intracarotid treatment Opening blood-brain-barrier

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Interplay between rabies virus and the mammalian immune system

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World Journal of Clinical Infectious Diseases 2015年第4期5卷 67-76页

作者： Nicholas Johnson Adam F Cunningham Animal and Plant Health Agency Institute of Microbiology and Infection School of Immunity and Infection University of Birmingham

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

关键词： Rabies virus Immune stimulation Central nervous system Vaccination blood-brain-barrier

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Evaluation of oxidative and nitrosative stress in relapsing remitting multiple sclerosis

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Health 2013年第11期5卷 1924-1928页

作者： Stefan Lukac Terezia Kalnovicova Jana Muchova Institute of Medical Chemistry Biochemistry and Clinical BiochemistryFaculty of MedicineComenius UniversityBratislavaSlovakia Department of Neurology Faculty of MedicineComenius UniversityBratislavaSlovakia

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

关键词： Relapsing Remiting Multiple Sclerosis Oxidative Stress Nitrative Stress blood-brain-barrier Total Antioxidant Status 3-Nitrotyrosine Protein Carbonyls Lipoperoxides Uric Acid

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