Inhalation anesthetic‐induced neuroinvasion by an attenuated strain of West Nile virus in mice

Abstract

There are contradictory reports regarding the effects of inhalation anesthetics on the immune system. Measurable immune responses have been studied in vitro, but little is known about the in vivo effects in the intact organism. We used an attenuated, non-neuroinvasive, nonlethal strain of the encephalitic West Nile virus, termed WN-25, which can become lethal in combination with environmental stressors, to study possible modulatory immune effects of inhalation anesthetics in mice. Both single short-term exposure and repeated exposure to halothane and nitrous oxide were studied. Exposure to 30% CO2 served as a positive control. Mortality, brain invasion, spleen weight, and antiviral antibodies served as the experimental endpoints. Halothane and nitrous oxide led to viral brain invasion, increased mortality, and suppressed immune response in a concentration- and time-dependent manner. Repeated exposures had a cumulative effect. Assessment of the stability of the viral attenuation did not demonstrate any alteration in the character of the virus, suggesting an increased access to the brain by inhalation anesthetics that led to the fatal encephalitis. These findings may be of special concern to populations at risk, such as operating room staff and patients undergoing general anesthesia in endemic areas of encephalitic virus species, in which subclinical infection may develop into an overt disease.

West Nile 25A virus infection of B-cell-deficient (μMT) mice: characterization of neuroinvasiveness and pseudoreversion of the viral envelope protein

“…Cell-mediated immune responses also play an important role in protection against WNV disease and virus clearance (Diamond et al, 2003;Shrestha & Diamond, 2004) and may contribute to the variable survival observed in the case of B-cell-deficient mice that do not rapidly succumb to infection with WN25A virus. A variety of physical stresses that are believed to have effects on the blood-brain barrier Kobiler et al, 1989;Katz et al, 2002) may also account for some of the variability in susceptibility observed here. In any case, the susceptibility of B-cell-deficient mice to WN25A virus is consistent with many previous reports, demonstrating a requirement for virus-specific antibodies to control flavivirus infection in various mouse challenge models (Mathews & Roehrig, 1984;Schlesinger et al, 1985;Brandriss et al, 1986;Phillpotts et al, 1987;KimuraKuroda & Yasui, 1988;Broom et al, 2000;Roehrig et al, 2001;Ben-Nathan et al, 2003).…”

Duck Tembusu virus exhibits neurovirulence in BALB/c mice

“…Several reports have shown that breaches in the BBB induced by sham i.c. inoculation or chemical reagents play an important role in CNS invasion by JEV and variant WNVs [22,27]. …”

Guidance for the Description of Animal Research in Scientific Publications

“…All preanesthetic agents, anesthetics, and analgesic drugs have the potential to induce numerous and varied effects on studies and consideration and discussion of these effects is warranted (Adams et al 2008;Avsaroglu et al 2007;Flecknell 1993;Hampshire et al 2001;Heavner 2003;Katz et al 2002;Murphy et al 2001;Nakai et al 2005;Suliburk et al 2005). If drugs are dosed to effect, the discussion will include strategies for dose determination as well as monitoring methods.…”