Graduate Institute of Clinical Medical Science, China Medical University.
Department of Anesthesiology, China Medical University Hospital.
Neuroreport. 2020 Jan 27;31(2):118-124. doi: 10.1097/WNR.0000000000001390.
Isoflurane protects the blood-brain barrier (BBB) against cerebral extravasation of Evans blue dye (EBD), a commonly used serum protein tracer, in animals subjected to BBB disruption. As such, it has been implicated as a therapeutic agent that can prevent brain edema and damage caused by a number of brain insults, including focal ischemia and subarachnoid hemorrhage. Recently, it has been shown that isoflurane inhibits the cerebral extravasation of EBD following ischemic stroke chiefly by inducing hypothermia, raising the intriguing possibility that isoflurane protected against other causes of BBB disruption also through hypothermia. To test this hypothesis, we subjected mice and rats to inhalation of 20-30% carbogen, an inducer of BBB disruption, in the presence or absence of isoflurane while measuring their rectal temperature. In mice, carbogen inhalation on its own decreased rectal temperature from 36.4 ± 0.4 to 26.2 ± 0.6°C over a period of 60 minutes, and under this condition, isoflurane had no additional effect on body temperature. Nevertheless, isoflurane protected against carbogen-induced cerebral extravasation of EBD. In addition, when the body temperature was maintained in the normothermic range using an automated heating pad, isoflurane remained protective against cerebral extravasation of EBD. In rats, isoflurane also protected against cerebral extravasation of EBD, while having no effect on plasma pH, electrolyte concentrations, or osmolarity. In conclusion, isoflurane protected against BBB disruption caused by carbogen inhalation in mice and rats, but unlike isoflurane-mediated protection against ischemic BBB disruption, the effect could not be explained by anesthesia-induced hypothermia.
异氟醚可保护血脑屏障（BBB）免受血脑屏障破坏动物中 Evans 蓝染料（EBD）的脑外渗， Evans 蓝染料是一种常用的血清蛋白示踪剂。因此，它被认为是一种治疗剂，可以预防脑水肿和许多脑损伤引起的损伤，包括局灶性缺血和蛛网膜下腔出血。最近，研究表明，异氟醚通过诱导体温降低来抑制缺血性中风后 EBD 的脑外渗，这提出了一个有趣的可能性，即异氟醚通过体温降低来保护血脑屏障免受其他原因的破坏。为了验证这一假说，我们在吸入 20-30%的碳化氧（一种血脑屏障破坏诱导剂）的同时，用或不用异氟醚处理小鼠和大鼠，并测量其直肠温度。在小鼠中，碳化氧吸入本身会在 60 分钟内将直肠温度从 36.4±0.4°C 降至 26.2±0.6°C，在这种情况下，异氟醚对体温没有额外的影响。然而，异氟醚可防止碳化氧诱导的 EBD 脑外渗。此外，当使用自动加热垫将体温维持在正常体温范围内时，异氟醚仍能防止 EBD 的脑外渗。在大鼠中，异氟醚也能防止 EBD 的脑外渗，同时对血浆 pH 值、电解质浓度或渗透压没有影响。总之，异氟醚可防止小鼠和大鼠因吸入碳化氧引起的血脑屏障破坏，但与异氟醚介导的缺血性血脑屏障破坏保护作用不同，这种作用不能用麻醉诱导的体温降低来解释。
