Noninvasive neurodegenerative disease treatments that open the blood–brain barrier (BBB), which prevents the passage of molecules that could induce cellular damage and inflammation in the brain, have been put forth as possible methods for therapeutic drug or gene delivery.

Researchers used MRI to determine how the brains of rats were affected by pulsed focused ultrasound (pFUS) combined with systemic ultrasound contrast agent microbubble (MB) treatment. Following pFUS+MB–induced BBB disruption, the authors found a number of proteomic and transcriptomic changes in the rat brains, including a release of damage-associated molecular patterns that led to a sterile inflammation response in the brain parenchyma.

Further histological analysis revealed that following pFUS+MB–induced BBB disruption levels of certain molecular and cellular markers of inflammation in the brain parenchyma and vasculature were elevated for up to 24 hours, and that the abundance of macrophages increased, consistent with an innate immune response.

The results suggest that pFUS+MB techniques might induce a sterile inflammatory response comparable to that of decreased blood supply or mild brain injury events. Further study might be required before pFUS+MB can be used in clinical settings, according to the authors.