Microbubble damage to the blood-brain barrier: relevance to decompression sickness

Decompression sickness affecting the nervous system is still a serious problem in diving, but the mechanisms involved are in dispute. Although microbubbles can be detected in the pulmonary artery on decompression using ultrasound, mammalian lungs are competent filters for microbubbles larger than 20 microns in diameter. It has been assumed that smaller bubbles released by the lungs are harmless, because there is evidence that they do not arrest in the cerebral circulation. We injected 15 +/- 5 microns diameter microbubbles in 5 ml of plasma slowly into the right carotid artery of anesthetized guinea pigs. At intervals of 1, 2, or 3 h postinjection, 2% trypan blue in 2 ml of plasma was injected into the same artery or the contralateral carotid artery. A control animal for each experiment was injected with 5 ml of plasma only, followed by the injection of dye at the same interval. After the animals were killed, the brains were examined for evidence of blood-brain barrier dysfunction. All animals at 1 h, and 9 out of 10 animals at 2 h after the injection of microbubbles, showed extravasation of the albumin-binding dye in the ipsilateral hemisphere, indicating gross blood-brain barrier dysfunction. In each of the matched controls, the barrier in the neocortex remained intact. At Hour 3 the barrier was impermeable to the trypan blue in both experimental and control animals. These experiments demonstrate that microbubbles impair the blood-brain barrier integrity to protein, causing focal edema.(ABSTRACT TRUNCATED AT 250 WORDS)