Correlation between breakdown of the blood–brain barrier and disease outcome of viral encephalitis in mice

Abstract

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.

Increased blood–brain barrier permeability is not a primary determinant for lethality of West Nile virus infection in rodents

“…Unlike SFV infection, the permeability began rising at 5 days p.i., which was 3 days (8 days p.i.) before animals started dying, which has been reported in a previous study (Olsen et al, 2007). Unexpectedly, a lethal infection of WNV in BALB/c mice did not affect the BBB within the sensitivity of the fluorescence assay (Fig.…”

“…However, we observed that only a subset of mice of this strain had increased permeability. Moreover, the levels and frequency of brain fluorescence of WNV-infected mice were lower than those for the positive control mice using another flavivirus (BANV) or an alphavirus (SFV) (Olsen et al, 2007). If BBB permeability were required for a lethal infection, then the onset of increased permeability would occur before the onset of death, which it did not.…”

“…For evaluation of BBB permeability to small molecular mass compounds in mice, the animals were injected with 10 mg sodium fluorescein (Sigma Aldrich) in 0.1 ml sterile saline, administered i.p. (Olsen et al, 2007). Animals were anaesthetized with ketamine HCl (100-200 mg kg 21 ) i.p.…”

“…This has been done with human immunodeficiency virus (Dallasta et al, 1999), simian immunodeficiency virus encephalitis (Luabeya et al, 2000) and a mouse model of experimental allergic encephalomyelitis induced by infection with an avirulent strain of Semliki Forest virus (SFV) (Eralinna et al, 1996). BBB permeability can also be assessed by measuring the leakage of indicator dyes or fluorescent molecules into the brain or CSF (Olsen et al, 2007). The question addressed in this study, using these methods, is whether increased BBB permeability in WNV-infected rodents is necessary for a lethal infection to occur.…”

Exercise Pre-conditioning Reduces Brain Inflammation and Protects against Toxicity Induced by Traumatic Brain Injury: Behavioral and Neurochemical Approach

“…administered (Olsen et al 2007). In brief, animals were anaesthetized with ketamine HCl (100-200 mg/kg) i.p.…”