Low intensity ultrasound inhibits brain oedema formation in rats: potential action on AQP4 membrane localization

Brain oedema is a major contributing factor to the morbidity and mortality of a variety of brain disorders. Although there has been considerable progress in our understanding of pathophysiological and molecular mechanisms associated with brain oedema so far, more effective treatment is required and is still awaited. Here we intended to study the effects of low intensity ultrasound (LIUS) on brain oedema.

We prepared the rat hippocampal slice in vitro and acute water intoxication in vivo models of brain oedema. We applied LIUS stimulation in these models and studied the molecular mechanisms of LIUS action on brain oedema.

We found that LIUS stimulation markedly inhibited the oedema formation in both of these models. LIUS stimulation significantly reduced brain water content and intracranial pressure resulting in increased survival of the rats. Here, we showed that the AQP4 localization was increased in the astrocytic foot processes in the oedematous hippocampal slices, while it was significantly reduced in the LIUS-stimulated hippocampal slices. In the in vivo model too, AQP4 expression was markedly increased in the microvessels of the cerebral cortex and hippocampus after water intoxication but was reduced in the LIUS-stimulated rats.

These data show that LIUS has an inhibitory effect on cytotoxic brain oedema and suggest its therapeutic potential to treat brain oedema. We propose that LIUS reduces the AQP4 localization around the astrocytic foot processes thereby decreasing water permeability into the brain tissue.