BackgroundRabies is known to be lethal in human. Treatment with passive immunity for the rabies is effective only when the patients have not shown the central nerve system (CNS) signs. The blood–brain barrier (BBB) is a complex functional barrier that may compromise the therapeutic development in neurological diseases. The goal of this study is to determine the change of BBB integrity and to assess the therapeutic possibility of enhancing BBB permeability combined with passive immunity in the late stage of rabies virus infection.MethodsThe integrity of BBB permeability in rats was measured by quantitative ELISA for total IgG and albumin levels in the cerebrospinal fluid (CSF) and by exogenously applying Evans blue as a tracer. Western blotting of occludin and ZO-1, two tight junction proteins, was used to assess the molecular change of BBB structure.The breakdown of BBB with hypertonic arabinose, recombinant tumor necrosis factor-alpha (rTNF-γ), and focused ultrasound (FUS) were used to compare the extent of BBB disruption with rabies virus infection. Specific humoral immunity was analyzed by immunofluorescent assay and rapid fluorescent focus inhibition test. Virus-neutralizing monoclonal antibody (mAb) 8-10E was administered to rats with hypertonic breakdown of BBB as a passive immunotherapy to prevent the death from rabies.ResultsThe BBB permeability was altered on day 7 post-infection. Increased BBB permeability induced by rabies virus infection was observed primarily in the cerebellum and spinal cord. Occludin was significantly decreased in both the cerebral cortex and cerebellum. The rabies virus-specific antibody was not strongly elicited even in the presence of clinical signs. Disruption of BBB had no direct association with the lethal outcome of rabies. Passive immunotherapy with virus-neutralizing mAb 8-10E with the hypertonic breakdown of BBB prolonged the survival of rabies virus-infected rats.ConclusionsWe demonstrated that the BBB permeability was altered in a rat model with rabies virus inoculation. Delivery of neutralizing mAb to the infected site in brain combined with effective breakdown of BBB could be an aggressive but feasible therapeutic mode in rabies when the CNS infection has been established.

BackgroundThrombosis and coagulopathy are the commonest hematological manifestations of envenomation of Russell’s viper venom (RVV). Factor X is activated by a factor X-activating enzyme from Russell’s viper venom (RVV-X) to start the coagulation cascade. We established an animal model with local ischemic effects induced by RVV. We tried to treat RVV envenomation with antiplatelets and anticoagulants without recourse to antivenom.MethodsRVV was injected into the foot pad of mice. We observed the effects at different intervals and compared local changes in ischemia with drug treatment after 30 min.ResultsA combination of aspirin plus tirofiban could prevent the ischemic change induced by RVV. The antithrombotic effects of single-use of aspirin or tirofiban were better than single-use of heparin or clopidogrel.ConclusionThe aspirin + tirofiban group had a better outcome with respect to prevention of tissue ischemia and gangrene. This indicates that the activation and aggregation of platelets is the major cause of thrombosis induced by RVV.