Ben-Nathan D, Kobiler D, Rzotkiewicz S, Lustig S, Katz Y
Dept. of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
Ann N Y Acad Sci. 2000;917:944-50. doi: 10.1111/j.1749-6632.2000.tb05460.x.
The effects of inhalational anesthetics on brain penetration by the neurovirulent noninvasive West Nile virus (WN-25) were studied in mice. WN-25 injected intracerebrally causes encephalitis and kills adult mice, but when injected intraperitoneally (i.p.) it is unable to invade the brain and kill. Under stress conditions, this strain causes encephalitis and death even after i.p. inoculation. In the study described in this paper, we used two inhalational anesthetics, a single short-term exposure to 2% halothane for 10 min in oxygen, or 70% nitrous oxide (N2O) for 30 min in air. Both inhalational anesthetics induced WN-25 encephalitis and death in 33% and 20% of the tested mice, respectively. Exposure of inoculated mice to halothane for prolonged periods or for repeated exposures (two or three times) markedly increased the mortality rate (up to 75%). Exposure to 30% CO2, a known modulator of blood-brain barrier (BBB) activity, was used as a positive control (80% mortality). No death was observed in the control non-exposed injected mice. Virus levels were found to be more than 10(7) plaque-forming units (PFU)/brain in all moribund mice. Additional parameter demonstrating the "stressor-like" nature of inhalation anesthetics was the induction of a significant decrease in weight of the lymphoid organs of inoculated mice. We suggest that inhalational anesthetics induces BBB breaching with subsequent entrance of the noninvasive WN-25 virus into the brain, causing encephalitis and death.
在小鼠中研究了吸入性麻醉剂对神经毒性非侵袭性西尼罗河病毒（WN - 25）脑渗透的影响。脑内注射WN - 25会引发脑炎并导致成年小鼠死亡，但腹腔注射时它无法侵入大脑并致死。在应激条件下，该毒株即使腹腔接种后也会引发脑炎和死亡。在本文所述的研究中，我们使用了两种吸入性麻醉剂，一种是在氧气中单次短期暴露于2%氟烷10分钟，另一种是在空气中暴露于70%氧化亚氮（N2O）30分钟。两种吸入性麻醉剂分别在33%和20%的受试小鼠中诱发了WN - 25脑炎和死亡。对接种小鼠长时间或重复（两次或三次）暴露于氟烷显著提高了死亡率（高达75%）。暴露于30%二氧化碳（一种已知的血脑屏障（BBB）活性调节剂）用作阳性对照（死亡率80%）。未暴露的对照注射小鼠未观察到死亡。在所有濒死小鼠中，病毒水平均超过10(7) 蚀斑形成单位（PFU）/脑。证明吸入性麻醉剂具有“应激源样”性质的另一个参数是接种小鼠淋巴器官重量显著下降。我们认为吸入性麻醉剂会导致血脑屏障破裂，随后非侵袭性WN - 25病毒进入大脑，引发脑炎和死亡。
