Disrupting the blood–brain barrier by focused ultrasound induces sterile inflammation

Abstract

Significance Pulsed focused ultrasound (pFUS) with systemic microbubble (MB) infusion is a noninvasive technique that opens the blood–brain barrier (BBB) and is currently advocated for increasing drug or gene delivery in neurological diseases. The opening of the BBB by pFUS+MB resulted in immediate damage-associated molecular patterns that led to a sterile inflammation response within the parenchyma that lasted 24 h. Currently, pFUS+MB exposure is under consideration as an adjuvant in the treatment in malignancy or neurodegenerative disease. These results demonstrate that pFUS+MB induces a sterile inflammatory response compatible with ischemia or mild traumatic brain injury. Further investigation will be required before translation to clinical trials.