Correlation between breakdown of the blood-brain barrier and disease outcome of viral encephalitis in mice.
Changes in the permeability of the blood-brain barrier (BBB) were evaluated in two mouse models of viral encephalitis. The ability of sodium fluorescein (NaFl) to cross the BBB from the serum into the central nervous system was assayed in animals inoculated with virulent strains of either Banzi or Semliki Forest viruses. To test the hypothesis that increases in BBB permeability were associated with poor disease outcome subsequent experiments measured BBB permeability in conjunction with treatment with the interferon inducer Ampligen (poly I:poly C(12)U). A single intraperitoneal injection of Ampligen (1 mg/kg) administered either 24 h or 4-6 h before, but not 24 h after, virus inoculation with Banzi virus provided significant improvements in survival, viral brain titers, weight change and BBB permeability. In comparison, a similar treatment with Ampligen administered either 24 h or 4-6 h before inoculation with Semliki Forest virus was able to significantly improve weight change, and BBB permeability, but only animals receiving Ampligen 4-6 h pre-virus showed a significantly improved mortality. In general, it was found that evaluation of BBB permeability was a more sensitive indicator of disease outcome and the antiviral efficacy Ampligen than either weight change or brain viral titers.
Olsen
Aaron L
AL
Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, 5600 Old Main Hill, Logan, UT 84322-5600, USA. alo@cc.usu.edu
Morrey
John D
JD
Smee
Donald F
DF
Sidwell
Robert W
RW
D018354:Alphavirus Infections / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000821:virology; D002199:Capillary Permeability / Q000187:drug effects; D018792:Encephalitis, Viral / Q000097:blood / Q000503:physiopathology* / Q000517:prevention & control; D005260:Female; D018177:Flavivirus Infections / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control; D019793:Fluorescein / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000821:virology; D008099:Liver / Q000187:drug effects / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D011070:Poly I-C / Q000627:therapeutic use; D011072:Poly U / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects / Q000821:virology; D016019:Survival Analysis; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D011072:Poly U; C047490:poly(I).poly(c12,U); D011070:Poly I-C; D019793:Fluorescein